Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
Purpose
This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.
Conditions
- Advanced Malignant Solid Neoplasm
- Anatomic Stage III Breast Cancer AJCC v8
- Anatomic Stage IV Breast Cancer AJCC v8
- Locally Advanced Malignant Solid Neoplasm
- Malignant Female Reproductive System Neoplasm
- Metastatic HER2-Negative Breast Carcinoma
- Metastatic Malignant Solid Neoplasm
- Recurrent Endometrial Carcinoma
- Recurrent Fallopian Tube Carcinoma
- Recurrent Malignant Female Reproductive System Neoplasm
- Recurrent Malignant Solid Neoplasm
- Recurrent Ovarian Carcinoma
- Recurrent Primary Peritoneal Carcinoma
- Unresectable HER2-Negative Breast Carcinoma
- Unresectable Malignant Solid Neoplasm
Eligibility
- Eligible Ages
- All ages
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Patient must have measurable disease
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
between 0-2 OR patient must have Lansky performance status of >= 50% or Karnofsky
performance status of >= 50%
- Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as
assessed by the enrolling provider
- All patients must have sequencing results available from a National Cancer Institute
(NCI) credentialed Designated Laboratory (DL)
- Patients must have locally advanced or advanced histologically documented solid
tumors requiring therapy and meet one of the following criteria:
- Patients must have progressed on at least one line of standard systemic therapy
OR
- Patients whose disease has no standard treatment that has been shown to prolong
overall survival
- Patient must meet one of the following requirements:
- Patients 18 years and older who have tumor amenable to minimal risk
image-guided or direct vision biopsy and must be willing and able to undergo a
tumor biopsy to obtain samples for research if the patient is to enroll in a
ComboMATCH treatment trial OR
- Patients 18 years and older who do not have disease that is biopsiable at
minimal risk to the patient must confirm availability of an archival tumor
tissue specimen for submission for research if the patient enrolls to a
ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
- Tissue must have been collected within 12 months prior to registration to
the EAY191 Registration Trial
- Patient must not have had a Response Evaluation Criteria in Solid Tumors
(RECIST) response (complete response [CR] or partial response [PR]) to any
intervening therapy after collection of the tissue
- Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be
available OR
- Patients under 18 years old must confirm availability of an archival tumor
tissue specimen for submission for research if patient enrolls to a ComboMATCH
Treatment Trial. This tumor tissue must meet the following criteria:
- Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be
available
- NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection
and management instructions. Performance of the mandatory research biopsy or
submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection
and submission of the blood specimens for the integrated studies will be
performed under the consent authority of the specific treatment trial protocol
to which the patient is registered. No procedures to collect specimens for
research only are to be performed for patients registered to the EAY191
Registration Trial only
- NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If
patient is found to not be eligible for the assigned ComboMATCH Treatment Trial,
indication of ineligibility will trigger re-evaluation and potential assignment to
another Treatment Trial
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Screening
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental EAY191-A2 (Cohort 1, Arm A) |
Cohort 1, Arm A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. |
|
|
Experimental EAY191-A2 (Cohort 2, Arm B) |
Cohort 2, Arm B: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. |
|
|
Experimental EAY191-A2 (Cohort 2, Arm C) |
Cohort 2, Arm C: Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. |
|
|
Experimental EAY191-A2 (Cohort 3, Arm D) |
Cohort 3, Arm D: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. |
|
|
Experimental EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib) |
Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up. |
|
|
Experimental EAY191-A3 Monotherapy Cohort 1 (binimetinib) |
Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up. |
|
|
Experimental EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations) |
Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or a FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated. |
|
|
Experimental EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations) |
Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated |
|
|
Experimental EAY191-E4 (taxane therapy) |
Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression. |
|
|
Experimental EAY191-E5 Cohort I Arm A (sotorasib, panitumumab) |
Patients receive sotorasib PO QD on days 1-28 and panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study. |
|
|
Active Comparator EAY191-E5 Cohort I Arm B (sotorasib) |
Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study. |
|
|
Experimental EAY191-E5 Cohort II (sotorasib) |
Patients receive combination therapy as in EAY191-E5 Arm A. |
|
|
Experimental EAY191-N2 Cohort I (Arm I) (NF1 mutations) |
Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study. |
|
|
Experimental EAY191-N2 Cohort I (Arm II) (NF1 mutations) |
Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study. |
|
|
Experimental EAY191-N2 Cohort II (NF1 mutations) |
Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study. |
|
|
Experimental EAY191-N4 Arm I (RAS pathway mutations) |
Patients receive selumetinib PO BID and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. |
|
|
Active Comparator EAY191-N4 Arm II (RAS pathway mutations) |
Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. |
|
|
Active Comparator EAY191-N5 Arm I (neratinib maleate) |
Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study. |
|
|
Experimental EAY191-N5 Arm II (neratinib maleate,palbociclib) |
Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study. |
|
|
Experimental EAY191-S3 (activating AKT mutation) |
Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up. |
|
Recruiting Locations
Birmingham, Alabama 35233
Mobile, Alabama 36688
Anchorage, Alaska 99508
Goodyear, Arizona 85338
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623-207-3000
Kingman, Arizona 86401
Phoenix, Arizona 85054
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855-776-0015
Jonesboro, Arkansas 72401
Arroyo Grande, California 93420
Carmichael, California 95608
Carmichael, California 95608
Elk Grove, California 95758
Encinitas, California 92024
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760-536-7700
La Jolla, California 92093
Los Angeles, California 90025
Los Angeles, California 90048
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310-423-8965
Orange, California 92868
Orange, California 92868
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714-734-6220
Palo Alto, California 94304
Rocklin, California 95765
Sacramento, California 95816
San Diego, California 92103
San Diego, California 92123
San Francisco, California 94158
Santa Monica, California 90404
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310-582-7448
Woodland, California 95695
Aurora, Colorado 80045
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720-848-0650
Fort Collins, Colorado 80524
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970-297-6150
Fort Collins, Colorado 80528
Greeley, Colorado 80631
Loveland, Colorado 80538
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970-203-7083
Newark, Delaware 19713
Newark, Delaware 19713
Aventura, Florida 33180
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954-461-2180
Coral Gables, Florida 33146
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305-243-2647
Deerfield Beach, Florida 33442
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Fort Lauderdale, Florida 33316
Gainesville, Florida 32610
Jacksonville, Florida 32224-9980
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Miami, Florida 33136
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Miami, Florida 33176
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Honolulu, Hawaii 96813
Honolulu, Hawaii 96813
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808-532-0315
Honolulu, Hawaii 96813
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Honolulu, Hawaii 96813
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‘Ewa Beach, Hawaii 96706
Boise, Idaho 83706
Boise, Idaho 83712
Caldwell, Idaho 83605
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Meridian, Idaho 83642
Nampa, Idaho 83687
Nampa, Idaho 83687
Post Falls, Idaho 83854
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Twin Falls, Idaho 83301
Barrington, Illinois 60010
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847-842-4847
Bloomington, Illinois 61704
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Carterville, Illinois 62918
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Chicago, Illinois 60608
Chicago, Illinois 60611
Chicago, Illinois 60612
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312-864-5204
Chicago, Illinois 60612
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312-355-3046
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815-285-7800
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708-226-4357
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217-545-7929
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Ankeny, Iowa 50023
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319-365-4673
Cedar Rapids, Iowa 52403
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Des Moines, Iowa 50314
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Des Moines, Iowa 50314
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Waukee, Iowa 50263
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Lexington, Kentucky 40509
Lexington, Kentucky 40536
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859-257-3379
Metairie, Louisiana 70006
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301-319-2100
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240-964-1400
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Ann Arbor, Michigan 48106
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Canton, Michigan 48188
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Flint, Michigan 48503
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Kalamazoo, Michigan 49007
Kalamazoo, Michigan 49009
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574-647-7370
Kalamazoo, Michigan 49048
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574-647-7370
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616-391-1230
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Pontiac, Michigan 48341
Reed City, Michigan 49677
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Saginaw, Michigan 48601
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Saint Joseph, Michigan 49085
Tawas City, Michigan 48764
Traverse City, Michigan 49684
Wyoming, Michigan 49519
Ypsilanti, Michigan 48106
Ypsilanti, Michigan 48197
Bemidji, Minnesota 56601
Coon Rapids, Minnesota 55433
Deer River, Minnesota 56636
Duluth, Minnesota 55805
Edina, Minnesota 55435
Hibbing, Minnesota 55746
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218-786-3308
Maple Grove, Minnesota 55369
Maplewood, Minnesota 55109
Minneapolis, Minnesota 55407
Rochester, Minnesota 55905
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855-776-0015
Saint Louis Park, Minnesota 55416
Saint Paul, Minnesota 55101
Saint Paul, Minnesota 55102
Sandstone, Minnesota 55072
Virginia, Minnesota 55792
Columbus, Mississippi 39705
Grenada, Mississippi 38901
Gulfport, Mississippi 39502
New Albany, Mississippi 38652
Oxford, Mississippi 38655
Southhaven, Mississippi 38671
Cape Girardeau, Missouri 63703
Chesterfield, Missouri 63017
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314-205-6936
City of Saint Peters, Missouri 63376
Creve Coeur, Missouri 63141
Farmington, Missouri 63640
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314-996-5569
Rolla, Missouri 65401
Saint Joseph, Missouri 64506
Sainte Genevieve, Missouri 63670
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314-996-5569
Springfield, Missouri 65804
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417-269-4520
St Louis, Missouri 63110
St Louis, Missouri 63128
St Louis, Missouri 63129
St Louis, Missouri 63131
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314-996-5569
St Louis, Missouri 63136
St Louis, Missouri 63141
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314-251-7066
Sullivan, Missouri 63080
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314-996-5569
Sunset Hills, Missouri 63127
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314-996-5569
Anaconda, Montana 59711
Billings, Montana 59101
Bozeman, Montana 59715
Great Falls, Montana 59405
Kalispell, Montana 59901
Missoula, Montana 59804
Henderson, Nevada 89052
Las Vegas, Nevada 89102
Las Vegas, Nevada 89135
Las Vegas, Nevada 89144
Las Vegas, Nevada 89148
Reno, Nevada 89502
Flemington, New Jersey 08822
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908-237-2330
Lakewood, New Jersey 08701
Livingston, New Jersey 07039
Long Branch, New Jersey 07740
Middletown, New Jersey 07748
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212-639-7592
New Brunswick, New Jersey 08903
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732-235-7356
Sewell, New Jersey 08080
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Toms River, New Jersey 08755
Albuquerque, New Mexico 87106
Buffalo, New York 14263
Commack, New York 11725
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212-639-7592
Harrison, New York 10604
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212-639-7592
Mineola, New York 11501
New York, New York 10016
New York, New York 10029
New York, New York 10065
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212-639-7592
Rochester, New York 14623
Syracuse, New York 13210
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315-464-5476
The Bronx, New York 10461
The Bronx, New York 10461
The Bronx, New York 10467
Asheboro, North Carolina 27205
Burlington, North Carolina 27215
Clinton, North Carolina 28328
Durham, North Carolina 27710
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888-275-3853
Goldsboro, North Carolina 27534
Greensboro, North Carolina 27403
Greensboro, North Carolina 27410
High Point, North Carolina 27262
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336-802-2500
Jacksonville, North Carolina 28546
Raleigh, North Carolina 27607
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919-785-4878
Reidsville, North Carolina 27320
Winston-Salem, North Carolina 27157
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336-713-6771
Bismarck, North Dakota 58501
Fargo, North Dakota 58122
Fargo, North Dakota 58122
Avon, Ohio 44011
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800-641-2422
Beachwood, Ohio 44122
Belpre, Ohio 45714
Canton, Ohio 44710
Centerville, Ohio 45459
Chillicothe, Ohio 45601
Cincinnati, Ohio 45220
Cleveland, Ohio 44106
Cleveland, Ohio 44111
Cleveland, Ohio 44195
Columbus, Ohio 43210
Columbus, Ohio 43213
Columbus, Ohio 43214
Columbus, Ohio 43214
Columbus, Ohio 43215
Columbus, Ohio 43219
Columbus, Ohio 43228
Dayton, Ohio 45409
Dayton, Ohio 45409
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937-276-8320
Dayton, Ohio 45415
Delaware, Ohio 43015
Delaware, Ohio 43015
Dublin, Ohio 43016
Dublin, Ohio 43016
Franklin, Ohio 45005-1066
Greenville, Ohio 45331
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937-569-7515
Kettering, Ohio 45429
Lancaster, Ohio 43130
Mansfield, Ohio 44903
Marion, Ohio 43302
Marysville, Ohio 43040
Mayfield Heights, Ohio 44124
Mentor, Ohio 44060
Mount Vernon, Ohio 43050
Newark, Ohio 43055
Perrysburg, Ohio 43551
Portsmouth, Ohio 45662
Springfield, Ohio 45504
Springfield, Ohio 45504
Toledo, Ohio 43623
Troy, Ohio 45373
Westerville, Ohio 43081
Zanesville, Ohio 43701
Oklahoma City, Oklahoma 73104
Newberg, Oregon 97132
Ontario, Oregon 97914
Oregon City, Oregon 97045
Portland, Oregon 97213
Portland, Oregon 97225
Portland, Oregon 97239
Allentown, Pennsylvania 18103
Bethlehem, Pennsylvania 18017
Bryn Mawr, Pennsylvania 19010
East Stroudsburg, Pennsylvania 18301
Erie, Pennsylvania 16505
Greensburg, Pennsylvania 15601
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724-838-1900
Hazleton, Pennsylvania 18201
Mechanicsburg, Pennsylvania 17050
Media, Pennsylvania 19063
Monroeville, Pennsylvania 15146
Paoli, Pennsylvania 19301
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19111
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215-728-4790
Pittsburgh, Pennsylvania 15213
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412-647-2811
Pittsburgh, Pennsylvania 15232
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412-647-8073
Pittsburgh, Pennsylvania 15237
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412-367-6454
Sayre, Pennsylvania 18840
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800-836-0388
Willow Grove, Pennsylvania 19090
Wynnewood, Pennsylvania 19096
Providence, Rhode Island 02905
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401-274-1122
Providence, Rhode Island 02908
Boiling Springs, South Carolina 29316
Columbia, South Carolina 29203
Easley, South Carolina 29640
Greenville, South Carolina 29601
Greenville, South Carolina 29605
Greenville, South Carolina 29605
Greenville, South Carolina 29605
Greenville, South Carolina 29607
Greenville, South Carolina 29615
Greer, South Carolina 29650
Seneca, South Carolina 29672
Rapid City, South Dakota 57701
Sioux Falls, South Dakota 57104
Sioux Falls, South Dakota 57117-5134
Collierville, Tennessee 38017
Kingsport, Tennessee 37660
Memphis, Tennessee 38120
Nashville, Tennessee 37204
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800-811-8480
Nashville, Tennessee 37232
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800-811-8480
Abilene, Texas 79601
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325-670-6340
Dallas, Texas 75390
Houston, Texas 77026-1967
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More Details
- NCT ID
- NCT05564377
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Detailed Description
PRIMARY OBJECTIVE: I. To register, allocate, and assign patients to ComboMATCH treatment trials. SECONDARY OBJECTIVES: I. To evaluate the rate of positive outcomes in defined cohorts within treatment trials of treatment combinations including targeted therapies for molecularly defined populations, and also in the subset of treatment trials where the treatments are supported by in vivo models. II. To perform quality control of the patients registered in the form of pathological confirmation of disease and sub-type to confirm diagnosis and treatment arm allocation. SECONDARY CORRELATIVE OBJECTIVES: I. Assess the concordance of the central molecular characterization of the pre-treatment biopsy samples with the genetic readouts from the Designated Laboratories (DLs) for patients enrolled on the ComboMATCH treatment trials. II. To assess how the registration diagnostic tumor mutation profile and pre-treatment biopsy profile compare to the circulating tumor-derived deoxyribonucleic acid (ctDNA) mutation profile from plasma. EXPLORATORY OBJECTIVE: I. Assess association between ComboMATCH treatment trials outcomes (positive or negative) with the type of rationale for the selected drug combinations and the type of rationale for the gene variant/combination for selection (e.g., whether the trial was based on targeted therapies for molecularly defined populations, those that were supported by in vivo models, and those that were supported by empiric clinical data). OUTLINE: REGISTRATION: Patients undergo tumor mutational screening of previously-collected tumor samples for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing. Patients who are 18 years or older and have biopsiable disease undergo a new biopsy for research purposes prior to initiating treatment on the ComboMATCH treatment trial. TREATMENT: Patients with mutations targeted to investigational combination therapies are assigned to 1 of 20 treatment subprotocols. EAY191-N4: Patients with RAS pathway mutant ovarian or endometrial cancer are randomized to 1 of 2 arms. ARM I: Patients receive selumetinib orally (PO) twice daily (BID) and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as echocardiogram (ECHO) or multigated acquisition (MUGA), and computed tomography (CT) scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. ARM II: Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. EAY191-N2: Patients with inactivating or inferred inactivating NF1 alterations, and hormone receptor positive, HER2-negative metastatic breast cancer. Patients who are fulvestrant naive are assigned to Cohort I, while patients who are fulvestrant resistant are assigned to Cohort II. COHORT I: Patients are randomized to 1 of 2 arms. ARM I:Patients receive fulvestrant intramuscularly (IM) on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, magnetic resonance imaging (MRI), or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study. ARM II: Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study. COHORT II: Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study. EAY191-E4: Patients with solid tumors who previously underwent taxane therapy. Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression. EAY191-A3: Patients with KRAS/NRAS/BRAF mutated low-grade serous ovarian cancer (LGSOC) naive to MEK or CDK4/6 inhibitor therapy are randomized to either combination cohort 1 or monotherapy cohort 1. Patients with LGSOC who have received prior MEK inhibitor therapy are assigned to combination cohort 2. Patients with KRAS/NRAS/HRAS/non-V600E BRAF mutated pancreatic cancer are assigned to combination cohort 3. Patients with all other KRAS/NRAS/HRAS mutated tumor types (excluding LGSOC, non-small cell lung cancer, colorectal cancer, pancreatic, and melanoma) are assigned to combination cohort 4. COMBINATION COHORTS 1, 2, 3, 4: Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up. MONOTHERAPY COHORT 1: Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up. EAY191-S3: Patients with an activating AKT mutation solid tumor. Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up. EAY191-A6: Patients with RAS/RAF/MEK/ERK mutant biliary tract cancers are randomized to 1 of 2 arms. ARM 1: Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo echocardiogram (ECHO) and multigated acquisition scan (MUGA) during screening and on study, a CT with contrast, MRI, or a fludeoxyglucose F-18 positron emission tomography (FDG-PET) during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated. ARM 2: Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated. EAY191-E5: Patients are assigned to 1 of 2 cohorts. COHORT I: Patients who have never received a KRAS G12C inhibitor are randomized to arms A or B. ARM A: Patients receive sotorasib PO once daily (QD) on days 1-28 and panitumumab intravenously IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study. ARM B: Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study. COHORT II: Patients who have received a KRAS G12C inhibitor are assigned to arm C. ARM C: Patients receive combination therapy as in Arm A. EAY191-A2: Patients are assigned to 1 of 3 cohorts. COHORT 1: PARP-inhibitor naive patients are assigned to Arm A. ARM A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. COHORT 2: PARP-inhibitor naive patients are randomized to 1 of 2 arms. ARM B: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. ARM C: Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. COHORT 3: PARP-inhibitor resistant patients are assigned to Arm D. ARM D: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. EAY191-N5: Patients are randomized to 1 of 2 arms. ARM I: Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study. ARM II: Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.