Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
About this trial
This is an interventional screening trial for Advanced Malignant Solid Neoplasm
Eligibility 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
Sites / Locations
- University of Alabama at Birmingham Cancer CenterRecruiting
- CTCA at Western Regional Medical CenterRecruiting
- Kingman Regional Medical CenterRecruiting
- PCR OncologyRecruiting
- Epic Care-DublinRecruiting
- Contra Costa Regional Medical CenterRecruiting
- Stanford Cancer Institute Palo AltoRecruiting
- UCSF Medical Center-Mission BayRecruiting
- Saint John's Cancer InstituteRecruiting
- Epic Care Cyberknife CenterRecruiting
- Presbyterian Intercommunity HospitalRecruiting
- Helen F Graham Cancer CenterRecruiting
- Medical Oncology Hematology Consultants PARecruiting
- Queen's Cancer Cenrer - POB IRecruiting
- Queen's Medical CenterRecruiting
- Straub Clinic and HospitalRecruiting
- Queen's Cancer Center - KuakiniRecruiting
- Saint Alphonsus Cancer Care Center-BoiseRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Saint Alphonsus Cancer Care Center-CaldwellRecruiting
- Kootenai Health - Coeur d'AleneRecruiting
- Saint Luke's Cancer Institute - FruitlandRecruiting
- Saint Luke's Cancer Institute - MeridianRecruiting
- Saint Luke's Cancer Institute - NampaRecruiting
- Saint Alphonsus Cancer Care Center-NampaRecruiting
- Kootenai Clinic Cancer Services - Post FallsRecruiting
- Kootenai Cancer ClinicRecruiting
- Saint Luke's Cancer Institute - Twin FallsRecruiting
- Advocate Good Shepherd HospitalRecruiting
- Illinois CancerCare-BloomingtonRecruiting
- Illinois CancerCare-CantonRecruiting
- Illinois CancerCare-CarthageRecruiting
- Centralia Oncology ClinicRecruiting
- Northwestern UniversityRecruiting
- John H Stroger Jr Hospital of Cook CountyRecruiting
- Advocate Illinois Masonic Medical CenterRecruiting
- AMG Crystal Lake - OncologyRecruiting
- Carle at The RiverfrontRecruiting
- Cancer Care Specialists of Illinois - DecaturRecruiting
- Decatur Memorial HospitalRecruiting
- Northwestern Medicine Cancer Center KishwaukeeRecruiting
- Illinois CancerCare-DixonRecruiting
- Advocate Good Samaritan HospitalRecruiting
- Carle Physician Group-EffinghamRecruiting
- Crossroads Cancer CenterRecruiting
- Advocate Sherman HospitalRecruiting
- Illinois CancerCare-EurekaRecruiting
- Illinois CancerCare-GalesburgRecruiting
- Northwestern Medicine Cancer Center DelnorRecruiting
- Advocate South Suburban HospitalRecruiting
- Illinois CancerCare-Kewanee ClinicRecruiting
- Northwestern Medicine Lake Forest HospitalRecruiting
- AMG Libertyville - OncologyRecruiting
- Condell Memorial HospitalRecruiting
- Illinois CancerCare-MacombRecruiting
- Carle Physician Group-Mattoon/CharlestonRecruiting
- Cancer Care Center of O'FallonRecruiting
- Advocate Christ Medical CenterRecruiting
- Illinois CancerCare-Ottawa ClinicRecruiting
- Advocate Lutheran General HospitalRecruiting
- Illinois CancerCare-PekinRecruiting
- Illinois CancerCare-PeoriaRecruiting
- Illinois CancerCare-PeruRecruiting
- Illinois CancerCare-PrincetonRecruiting
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Carle Cancer CenterRecruiting
- Northwestern Medicine Cancer Center WarrenvilleRecruiting
- Illinois CancerCare - WashingtonRecruiting
- Mercy HospitalRecruiting
- Oncology Associates at Mercy Medical CenterRecruiting
- Medical Oncology and Hematology Associates-Des MoinesRecruiting
- Mercy Medical Center - Des MoinesRecruiting
- Saint Joseph Hospital EastRecruiting
- Ochsner Medical Center JeffersonRecruiting
- Lafayette Family Cancer Center-EMMCRecruiting
- National Institutes of Health Clinical CenterRecruiting
- UPMC Western MarylandRecruiting
- Tufts Medical CenterRecruiting
- Baystate Medical CenterRecruiting
- Saint Joseph Mercy HospitalRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
- Saint Joseph Mercy CantonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
- Saint Joseph Mercy ChelseaRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
- Beaumont Hospital - DearbornRecruiting
- Beaumont Hospital - Farmington HillsRecruiting
- Genesee Cancer and Blood Disease Treatment CenterRecruiting
- Genesee Hematology Oncology PCRecruiting
- Genesys Hurley Cancer InstituteRecruiting
- Hurley Medical CenterRecruiting
- Sparrow HospitalRecruiting
- Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
- William Beaumont Hospital-Royal OakRecruiting
- William Beaumont Hospital - TroyRecruiting
- Huron Gastroenterology PCRecruiting
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
- Sanford Joe Lueken Cancer CenterRecruiting
- Mercy HospitalRecruiting
- Essentia Health - Deer River ClinicRecruiting
- Essentia Health Cancer CenterRecruiting
- Fairview Southdale HospitalRecruiting
- Essentia Health Hibbing ClinicRecruiting
- Abbott-Northwestern HospitalRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- United HospitalRecruiting
- Essentia Health SandstoneRecruiting
- Essentia Health Virginia ClinicRecruiting
- Saint Francis Medical CenterRecruiting
- Saint Luke's HospitalRecruiting
- Parkland Health Center - FarmingtonRecruiting
- Washington University School of MedicineRecruiting
- Missouri Baptist Medical CenterRecruiting
- Mercy Hospital Saint LouisRecruiting
- Sainte Genevieve County Memorial HospitalRecruiting
- Missouri Baptist Sullivan HospitalRecruiting
- Missouri Baptist Outpatient Center-Sunset HillsRecruiting
- Community Hospital of AnacondaRecruiting
- Billings Clinic Cancer CenterRecruiting
- Bozeman Deaconess HospitalRecruiting
- Benefis Healthcare- Sletten Cancer InstituteRecruiting
- Kalispell Regional Medical CenterRecruiting
- Community Medical HospitalRecruiting
- OptumCare Cancer Care at CharlestonRecruiting
- Alliance for Childhood Diseases/Cure 4 the Kids FoundationRecruiting
- Summerlin Hospital Medical CenterRecruiting
- OptumCare Cancer Care at Fort ApacheRecruiting
- Renown Regional Medical CenterRecruiting
- Memorial Sloan Kettering MonmouthRecruiting
- Rutgers Cancer Institute of New JerseyRecruiting
- Sidney Kimmel Cancer Center Washington TownshipRecruiting
- University of New Mexico Cancer CenterRecruiting
- Montefiore Medical Center-Einstein CampusRecruiting
- Montefiore Medical Center-Weiler HospitalRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Roswell Park Cancer InstituteRecruiting
- Memorial Sloan Kettering CommackRecruiting
- Memorial Sloan Kettering WestchesterRecruiting
- Mount Sinai HospitalRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- Sanford Bismarck Medical CenterRecruiting
- Sanford Broadway Medical CenterRecruiting
- Sanford Roger Maris Cancer CenterRecruiting
- UH Seidman Cancer Center at UH Avon Health CenterRecruiting
- UHHS-Chagrin Highlands Medical CenterRecruiting
- Strecker Cancer Center-BelpreRecruiting
- Aultman Health FoundationRecruiting
- Miami Valley Hospital SouthRecruiting
- Adena Regional Medical CenterRecruiting
- Case Western Reserve UniversityRecruiting
- Mount Carmel East HospitalRecruiting
- The Mark H Zangmeister CenterRecruiting
- Fairfield Medical CenterRecruiting
- UH Seidman Cancer Center at Lake Health Mentor CampusRecruiting
- UH Seidman Cancer Center at Southwest General HospitalRecruiting
- Knox Community HospitalRecruiting
- Licking Memorial HospitalRecruiting
- Mercy Health Perrysburg Cancer CenterRecruiting
- Southern Ohio Medical CenterRecruiting
- Springfield Regional Cancer CenterRecruiting
- Springfield Regional Medical CenterRecruiting
- Mercy Health - Saint Anne HospitalRecruiting
- Toledo Clinic Cancer Centers-ToledoRecruiting
- Saint Ann's HospitalRecruiting
- Genesis Healthcare System Cancer Care CenterRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Providence Newberg Medical CenterRecruiting
- Saint Alphonsus Medical Center-OntarioRecruiting
- Providence Willamette Falls Medical CenterRecruiting
- Providence Portland Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Oregon Health and Science UniversityRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- UPMC AltoonaRecruiting
- Lehigh Valley Hospital - MuhlenbergRecruiting
- Bryn Mawr HospitalRecruiting
- Pocono Medical CenterRecruiting
- UPMC Hillman Cancer Center ErieRecruiting
- UPMC Cancer Centers - Arnold Palmer PavilionRecruiting
- UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer PavilionRecruiting
- Riddle Memorial HospitalRecruiting
- UPMC Hillman Cancer Center - MonroevilleRecruiting
- Paoli Memorial HospitalRecruiting
- Thomas Jefferson University HospitalRecruiting
- University of Pittsburgh Cancer Institute (UPCI)Recruiting
- UPMC-Passavant HospitalRecruiting
- Asplundh Cancer PavilionRecruiting
- Lankenau Medical CenterRecruiting
- Women and Infants HospitalRecruiting
- Prisma Health Cancer Institute - SpartanburgRecruiting
- Prisma Health Cancer Institute - EasleyRecruiting
- BI-LO Charities Children's Cancer CenterRecruiting
- Prisma Health Cancer Institute - ButternutRecruiting
- Prisma Health Cancer Institute - FarisRecruiting
- Prisma Health Cancer Institute - EastsideRecruiting
- Prisma Health Cancer Institute - GreerRecruiting
- Prisma Health Cancer Institute - SenecaRecruiting
- Sanford Cancer Center Oncology ClinicRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- M D Anderson Cancer CenterRecruiting
- Virginia Cancer InstituteRecruiting
- VCU Massey Cancer Center at Stony PointRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- VCU Community Memorial Health CenterRecruiting
- Valley Medical CenterRecruiting
- Swedish Medical Center-First HillRecruiting
- North Star Lodge Cancer Center at Yakima Valley Memorial HospitalRecruiting
- West Virginia University HealthcareRecruiting
- ThedaCare Regional Cancer CenterRecruiting
- ThedaCare Regional Medical Center - AppletonRecruiting
- Duluth Clinic AshlandRecruiting
- ThedaCare Cancer Care - BerlinRecruiting
- Aurora Cancer Care-Southern Lakes VLCCRecruiting
- Aurora Health Care Germantown Health CenterRecruiting
- Aurora Cancer Care-GraftonRecruiting
- Aurora BayCare Medical CenterRecruiting
- Aurora Cancer Care-Kenosha SouthRecruiting
- Gundersen Lutheran Medical CenterRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Aurora Bay Area Medical Group-MarinetteRecruiting
- Aurora Cancer Care-MilwaukeeRecruiting
- Aurora Saint Luke's Medical CenterRecruiting
- Aurora Sinai Medical CenterRecruiting
- ProHealth D N Greenwald CenterRecruiting
- ThedaCare Regional Medical Center - NeenahRecruiting
- ThedaCare Cancer Care - New LondonRecruiting
- ProHealth Oconomowoc Memorial HospitalRecruiting
- ThedaCare Cancer Care - OshkoshRecruiting
- Vince Lombardi Cancer Clinic - OshkoshRecruiting
- Aurora Cancer Care-RacineRecruiting
- ThedaCare Cancer Care - ShawanoRecruiting
- Vince Lombardi Cancer Clinic-SheboyganRecruiting
- Aurora Medical Center in SummitRecruiting
- Vince Lombardi Cancer Clinic-Two RiversRecruiting
- UW Cancer Center at ProHealth CareRecruiting
- ThedaCare Cancer Care - WaupacaRecruiting
- Aurora Cancer Care-Milwaukee WestRecruiting
- Aurora West Allis Medical CenterRecruiting
- Doctors Cancer CenterRecruiting
- Centro Comprensivo de Cancer de UPRRecruiting
- PROncologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Arm 16
Arm 17
Arm 18
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Active Comparator
Experimental
EAY191-A2 (Cohort 1, Arm A)
EAY191-A2 (Cohort 2, Arm B)
EAY191-A2 (Cohort 2, Arm C)
EAY191-A2 (Cohort 3, Arm D)
EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)
EAY191-A3 Monotherapy Cohort 1 (binimetinib)
EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations)
EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations)
EAY191-E4 (taxane therapy)
EAY191-E5 Cohort I Arm B (panitumumab)
EAY191-E5 Cohort I Arm I (sotorasib, panitumumab)
EAY191-E5 Cohort II (sotorasib)
EAY191-N2 Cohort I (Arm I) (NF1 mutations)
EAY191-N2 Cohort I (Arm II) (NF1 mutations)
EAY191-N2 Cohort II (NF1 mutations)
EAY191-N4 Arm I (RAS pathway mutations)
EAY191-N4 Arm II (RAS pathway mutations)
EAY191-S3 (activating AKT mutation)
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.
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.
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.
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.
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.
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.
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.
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
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.
Patients receive sotorasib PO on study. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples and a tumor biopsy before treatment and CT or MRI at follow up.
Patients receive sotorasib PO and panitumumab IV on study. Patients also undergo collection of blood samples and a tumor biopsy before treatment and CT or MRI at follow up.
Patients receive combination therapy as in EAY191-E5 Arm A.
Patients receive fulvestrant IM and binimetinib PO throughout the trial. Patients also undergo a CT, MRI, or bone scan and tumor biopsy during screening and on study.
Patients receive fulvestrant IM throughout the trial. Patients who progress on fulvestrant alone are asked to reaffirm their willingness to enroll in cohort II. Patients not willing to transition to cohort II continue further therapy as clinically indicated. Patients undergo a CT, MRI, or bone scan and tumor biopsy during screening and on study.
Patients receive fulvestrant IM and binimetinib PO throughout the trial. If the patient progressed on fulvestrant, the loading dose of fulvestrant is omitted. Patients undergo a CT, MRI, or bone scan and tumor biopsy during screening and on study.
Patients receive selumetinib PO and olaparib PO on study. 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.
Patients receive selumetinib PO on study. 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.
Patients receive paclitaxel IV and ipatasertib PO on study. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and follow-up.