Various Cancer Types

EAY191-E5



Testing the use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)

STATUS: Closed to Accrual


This phase II ComboMATCH treatment trial tests how well AMG 510 (sotorasib) with or without panitumumab works in treating patients with KRAS G12C mutant solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Sotorasib is in a class of medications called KRAS inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells. Panitumumab is in a class of medications called monoclonal antibodies. It works by slowing or stopping the growth of cancer cells. Giving combination panitumumab and sotorasib may kill more tumor cells in patients with advanced solid tumors with KRAS G12C mutation.
  • Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-E5 based on the presence of an actionable mutation as defined in EAY191

  • Patient must be enrolled on the ComboMATCH Registration Protocol (EAY191) at the time of registration/randomization to the EAY191-E5 study

  • Patient must be >= 18 years of age

  • Patient must have a KRAS G12C alteration as determined by the ComboMATCH screening assessment

  • Patient must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191-E5) * NOTE: The current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website: www.ctsu.org (final URL pending) * NOTE: Novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH registration protocol

  • Patient must have cytologically/histologically confirmed advanced/metastatic solid tumor

  • Patient must have progressed on at least one line of standard of care therapy in the advanced/metastatic setting * NOTE: Patients who have progressed on a prior human epidermal growth factor receptor (EGFR) inhibitor will meet this criterion

  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 (or Karnofsky performance status >= 60%)

  • Patient must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) documented by imaging obtained within 28 days prior to registration/randomization

  • Patient must not have any serious active infection within 4 weeks prior to EAY191-E5 registration/randomization (e.g., requiring hospitalization and/or intravenous [IV] antibiotics) or currently receiving oral or IV antibiotics for the treatment of infection. Patients receiving prophylactic antibiotics are eligible

  • Patient must have the ability to retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption

  • Patient must not have any history of or current evidence of non-infectious interstitial lung disease (ILD)/pneumonitis

  • Patient must not have a history of allergic reactions attributed to either of the study agents or to agents of similar chemical or biologic composition

  • Patient must have completed full treatment cycle 21 days prior to EAY191-E5 registration/randomization if they have received prior chemotherapy, biological cancer therapy, radiation therapy or an investigational agent/device. Patients must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse events due to prior cancer therapy (with the exception of alopecia)

  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration/randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

  • Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 6 months after the last dose of protocol treatment. Patients must not breastfeed while receiving protocol treatment and for one week (7 days) after the last dose of AMG 510 (sotorasib) and 2 months after the last dose of panitumumab

  • Patients must not have neuropathy ≥ grade 2 within 14 days prior to registration/randomization

  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression

  • Human immunodeficiency virus (HIV)-infected patients no effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

  • Patients with known history or current symptoms of cardiac history, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trail, patients should be class 2B or better

  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 28 days prior to protocol registration/randomization)

  • Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase ([SGPT]) < 3 x institutional upper limit of normal (obtained ≤ 28 days prior to protocol registration/randomization)

  • Creatinine =< 1.5 x institutional ULN OR creatinine clearance > 50 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 mg/dL as per Cockcroft-Gault (obtained ≤ 28 days prior to protocol registration/randomization)

  • COHORT I: Patient must not have colorectal cancer or non-small cell lung cancer

  • COHORT I: Patient must not have been previously treated with a KRAS G12C inhibitor

  • COHORT II: Patient must have progressed after treatment at the recommended phase II dose (RP2D) of any KRAS G12C inhibitor * NOTE: Patients on cohort 1 who experience progression on Regimen 2 (AMG 510 [sotorasib] alone) may be eligible to enroll on cohort 2 and receive combination treatment with panitumumab and AMG 510 (sotorasib). Patients must meet performance status requirements and laboratory values as above and must be begin treatment within 7 days of enrollment. Migration to cohort 2 must take place within 6 months of progression, with no intervening anti-cancer therapy given. * NOTE: Cohort migration following disease progression is dependent on a slot being available. MATCHBox makes the new treatment assignment following initiation of a step 2 registration for this treatment trial

  • COHORT II: Patient must not have been previously treated with a KRAS G12C inhibitor in combination with an EGFR inhibitor

United States
AL
Birmingham
University of Alabama at Birmingham Cancer Center
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Mobile
University of South Alabama Mitchell Cancer Institute
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CA
Los Angeles
Cedars-Sinai Medical Center
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The Angeles Clinic and Research Institute - West Los Angeles Office
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Palo Alto
VA Palo Alto Health Care System
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FL
Aventura
UM Sylvester Comprehensive Cancer Center at Aventura
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Coral Gables
UM Sylvester Comprehensive Cancer Center at Coral Gables
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Coral Springs
UM Sylvester Comprehensive Cancer Center at Coral Springs
Contact: Site Public Contact

Deerfield Beach
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Contact: Site Public Contact

Hollywood
UM Sylvester Comprehensive Cancer Center at Hollywood
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Jacksonville
Mayo Clinic in Florida
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Miami
UM Sylvester Comprehensive Cancer Center at Kendall
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University of Miami Miller School of Medicine-Sylvester Cancer Center
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Plantation
UM Sylvester Comprehensive Cancer Center at Plantation
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IA
Ankeny
UI Health Care Mission Cancer and Blood - Ankeny Clinic
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Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic
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UI Health Care Mission Cancer and Blood - Laurel Clinic
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Waukee
UI Health Care Mission Cancer and Blood - Waukee Clinic
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ID
Boise
Saint Alphonsus Cancer Care Center-Boise
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Email: [email protected]

Saint Luke's Cancer Institute - Boise
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Caldwell
Saint Alphonsus Cancer Care Center-Caldwell
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Email: [email protected]

Coeur D'Alene
Kootenai Health - Coeur d'Alene
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Email: [email protected]

Fruitland
Saint Luke's Cancer Institute - Fruitland
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Email: [email protected]

Meridian
Saint Luke's Cancer Institute - Meridian
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Nampa
Saint Alphonsus Cancer Care Center-Nampa
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Email: [email protected]

Saint Luke's Cancer Institute - Nampa
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Post Falls
Kootenai Clinic Cancer Services - Post Falls
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Sandpoint
Kootenai Clinic Cancer Services - Sandpoint
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Email: [email protected]

IL
Barrington
Advocate Good Shepherd Hospital
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Chicago
Advocate Illinois Masonic Medical Center
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John H Stroger Jr Hospital of Cook County
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University of Illinois
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Crystal Lake
AMG Crystal Lake - Oncology
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Email: [email protected]

Danville
Carle at The Riverfront
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Decatur
Cancer Care Specialists of Illinois - Decatur
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Decatur Memorial Hospital
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Downers Grove
Advocate Good Samaritan Hospital
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Effingham
Carle Physician Group-Effingham
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Email: [email protected]

Crossroads Cancer Center
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Elgin
Advocate Sherman Hospital
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Hazel Crest
Advocate South Suburban Hospital
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Libertyville
AMG Libertyville - Oncology
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Condell Memorial Hospital
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Mattoon
Carle Physician Group-Mattoon/Charleston
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Maywood
Loyola University Medical Center
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Normal
Carle BroMenn Medical Center
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Carle Cancer Institute Normal
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O'Fallon
Cancer Care Center of O'Fallon
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Email: [email protected]

Oak Lawn
Advocate Christ Medical Center
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Advocate Outpatient Center - Oak Lawn
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Palos Heights
Advocate High Tech Medical Park
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Park Ridge
Advocate Lutheran General Hospital
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Shiloh
Memorial Hospital East
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Springfield
Southern Illinois University School of Medicine
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Springfield Clinic
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Springfield Memorial Hospital
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Urbana
Carle Cancer Center
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KY
Lexington
University of Kentucky/Markey Cancer Center
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MD
Baltimore
University of Maryland/Greenebaum Cancer Center
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Bethesda
National Institutes of Health Clinical Center
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Walter Reed National Military Medical Center
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ME
Brewer
Lafayette Family Cancer Center-EMMC
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MI
Ann Arbor
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Email: [email protected]

Brighton
Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Email: [email protected]

Trinity Health Medical Center - Brighton
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Email: [email protected]

Canton
Trinity Health IHA Medical Group Hematology Oncology - Canton
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Email: [email protected]

Trinity Health Medical Center - Canton
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Email: [email protected]

Chelsea
Chelsea Hospital
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Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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Email: [email protected]

Dearborn
Corewell Health Dearborn Hospital
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Farmington Hills
Corewell Health Farmington Hills Hospital
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Flint
Cancer Hematology Centers - Flint
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Email: [email protected]

Genesee Hematology Oncology PC
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Genesys Hurley Cancer Institute
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Hurley Medical Center
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Lansing
University of Michigan Health - Sparrow Lansing
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Livonia
Trinity Health Saint Mary Mercy Livonia Hospital
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Pontiac
Trinity Health Saint Joseph Mercy Oakland Hospital
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Email: [email protected]

Royal Oak
Corewell Health Children's
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Corewell Health William Beaumont University Hospital
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Saginaw
MyMichigan Medical Center Saginaw
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Email: [email protected]

Oncology Hematology Associates of Saginaw Valley PC
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Email: [email protected]

Tawas City
MyMichigan Medical Center Tawas
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Email: [email protected]

Troy
Corewell Health Beaumont Troy Hospital
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West Branch
Saint Mary's Oncology/Hematology Associates of West Branch
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Ypsilanti
Huron Gastroenterology PC
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Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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Email: [email protected]

MN
Deer River
Essentia Health - Deer River Clinic
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Email: [email protected]

Duluth
Essentia Health Cancer Center
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Email: [email protected]

Hibbing
Essentia Health Hibbing Clinic
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Rochester
Mayo Clinic in Rochester
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Sandstone
Essentia Health Sandstone
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Email: [email protected]

Virginia
Essentia Health Virginia Clinic
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MO
Cape Girardeau
Saint Francis Medical Center
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Email: [email protected]

Creve Coeur
Siteman Cancer Center at West County Hospital
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Email: [email protected]

Saint Louis
Siteman Cancer Center at Christian Hospital
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Email: [email protected]

Siteman Cancer Center-South County
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Email: [email protected]

Washington University School of Medicine
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Saint Peters
Siteman Cancer Center at Saint Peters Hospital
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Email: [email protected]

MT
Anaconda
Community Hospital of Anaconda
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Billings
Billings Clinic Cancer Center
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Email: [email protected]

Bozeman
Bozeman Health Deaconess Hospital
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Great Falls
Benefis Sletten Cancer Institute
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Kalispell
Logan Health Medical Center
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Missoula
Community Medical Center
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NJ
New Brunswick
Rutgers Cancer Institute of New Jersey
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NM
Albuquerque
University of New Mexico Cancer Center
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Email: [email protected]

NV
Las Vegas
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
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Email: [email protected]

OptumCare Cancer Care at Charleston
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Email: [email protected]

OptumCare Cancer Care at Fort Apache
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Email: [email protected]

NY
Buffalo
Roswell Park Cancer Institute
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Email: [email protected]

Mineola
NYU Langone Hospital - Long Island
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Email: [email protected]

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Email: [email protected]

OH
Columbus
Columbus Oncology and Hematology Associates Inc
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Email: [email protected]

Doctors Hospital
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Grant Medical Center
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Riverside Methodist Hospital
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Dayton
Dayton Physician LLC - Englewood
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Email: [email protected]

Delaware
Delaware Health Center-Grady Cancer Center
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Email: [email protected]

Grady Memorial Hospital
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Email: [email protected]

Dublin
Columbus Oncology and Hematology Associates
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Email: [email protected]

Dublin Methodist Hospital
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Kettering
Kettering Medical Center
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Email: [email protected]

Mansfield
OhioHealth Mansfield Hospital
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Marion
OhioHealth Marion General Hospital
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Email: [email protected]

OK
Oklahoma City
University of Oklahoma Health Sciences Center
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Email: [email protected]

OR
Ontario
Saint Alphonsus Cancer Care Center-Ontario
Contact: Site Public Contact
Email: [email protected]

Portland
Providence Portland Medical Center
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Email: [email protected]

Providence Saint Vincent Medical Center
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PA
Philadelphia
Thomas Jefferson University Hospital
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Willow Grove
Asplundh Cancer Pavilion
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Email: [email protected]

SC
Boiling Springs
Prisma Health Cancer Institute - Spartanburg
Contact: Site Public Contact
Email: [email protected]

Easley
Prisma Health Cancer Institute - Easley
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Email: [email protected]

Greenville
Prisma Health Cancer Institute - Butternut
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Email: [email protected]

Prisma Health Cancer Institute - Eastside
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Email: [email protected]

Prisma Health Cancer Institute - Faris
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Email: [email protected]

Greer
Prisma Health Cancer Institute - Greer
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Email: [email protected]

Seneca
Prisma Health Cancer Institute - Seneca
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Email: [email protected]

SD
Rapid City
Rapid City Regional Hospital
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Email: [email protected]

TN
Bristol
Bristol Regional Medical Center
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Email: [email protected]

Johnson City
Regional Cancer Center at Johnson City Medical Center
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Email: [email protected]

Kingsport
Ballad Health Cancer Care - Kingsport
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Email: [email protected]

Wellmont Holston Valley Hospital and Medical Center
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Nashville
Vanderbilt University/Ingram Cancer Center
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TX
Temple
Scott and White Memorial Hospital
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VA
Bristol
Ballad Health Cancer Care - Bristol
Contact: Site Public Contact
Email: [email protected]

Charlottesville
University of Virginia Cancer Center
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Email: [email protected]

Richmond
VCU Massey Cancer Center at Stony Point
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Email: [email protected]

VCU Massey Comprehensive Cancer Center
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Email: [email protected]

WI
Appleton
ThedaCare Regional Cancer Center
Contact: Site Public Contact
Email: [email protected]

Ashland
Duluth Clinic Ashland
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Email: [email protected]

Berlin
ThedaCare Cancer Care - Berlin
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Email: [email protected]

Burlington
Aurora Cancer Care-Southern Lakes VLCC
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Email: [email protected]

Cudahy
Aurora Saint Luke's South Shore
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Email: [email protected]

Germantown
Aurora Health Care Germantown Health Center
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Email: [email protected]

Grafton
Aurora Cancer Care-Grafton
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Email: [email protected]

Green Bay
Aurora BayCare Medical Center
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Email: [email protected]

Janesville
Mercyhealth Hospital and Cancer Center - Janesville
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Email: [email protected]

Kenosha
Aurora Cancer Care-Kenosha South
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Email: [email protected]

La Crosse
Gundersen Lutheran Medical Center
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Email: [email protected]

Madison
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
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Email: [email protected]

University of Wisconsin Carbone Cancer Center - University Hospital
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Email: [email protected]

Marinette
Aurora Bay Area Medical Group-Marinette
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Email: [email protected]

Milwaukee
Aurora Cancer Care-Milwaukee
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Email: [email protected]

Aurora Saint Luke's Medical Center
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Aurora Sinai Medical Center
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Neenah
ThedaCare Regional Medical Center - Neenah
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Email: [email protected]

New London
ThedaCare Cancer Care - New London
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Email: [email protected]

Oshkosh
ThedaCare Cancer Care - Oshkosh
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Email: [email protected]

Vince Lombardi Cancer Clinic - Oshkosh
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Email: [email protected]

Racine
Aurora Cancer Care-Racine
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Email: [email protected]

Shawano
ThedaCare Cancer Care - Shawano
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Email: [email protected]

Sheboygan
Vince Lombardi Cancer Clinic-Sheboygan
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Email: [email protected]

Summit
Aurora Medical Center in Summit
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Email: [email protected]

Two Rivers
Vince Lombardi Cancer Clinic-Two Rivers
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Email: [email protected]

Waupaca
ThedaCare Cancer Care - Waupaca
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Email: [email protected]

Wauwatosa
Aurora Cancer Care-Milwaukee West
Contact: Site Public Contact
Email: [email protected]

West Allis
Aurora West Allis Medical Center
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Email: [email protected]

WV
Charleston
West Virginia University Charleston Division
Contact: Site Public Contact

PRIMARY OBJECTIVES:
I. To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab as compared to AMG 510 (sotorasib) alone in patients with advanced/metastatic KRAS G12C mutated solid tumors (except colorectal carcinoma [CRC] and non-small cell lung carcinoma [NSCLC]) as measured by progression free survival (Cohort 1).
II. To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab in patients with advanced/metastatic KRAS G12C mutated solid tumors that have progressed on a prior KRAS G12C inhibitor as measured by response rate (Cohort 2).

SECONDARY OBJECTIVES:
I. To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab as compared to AMG 510 alone in patients with advanced/metastatic KRAS G12C mutated solid tumors (except CRC and NSCLC) as measured by response rate, disease control rate, and overall survival (Cohort 1).
II, To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab in patients with advanced/metastatic KRAS G12C mutated solid tumors that have progressed on a prior KRAS G12C inhibitor as measured by disease control rate, progression free survival (PFS), and overall survival (Cohort 2).
III. To further evaluate the safety and tolerability of the combination of AMG 510 (sotorasib) and panitumumab.
IV. To collect tissue and provide it to the ComboMATCH Registration Protocol to assess concordance between the diagnostic tumor mutation profile generated by the Designated Laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration Protocol.

CORRELATIVE EXPLORATORY OBJECTIVES:
I. To investigate the impact of concomitant mutations on the clinical benefit.
II. To evaluate if changes in circulating tumor DNA (ctDNA) over time correlate with response to treatment.
III. To evaluate the relative mutant allele fraction of KRAS mutation as a predictor of clinical benefit.
IV. To evaluate if ERK 1/2 and PI3K pathway activation correlate with response and/or resistance.

OUTLINE: 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 orally (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 computed tomography (CT) or magnetic resonance imaging (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.

After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 36 months.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed and conducted this trial with funding from the National Cancer Institute through its National Clinical Trials Network. This trial is part of the ComboMATCH precision medicine intiative.