BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study

Melanoma Clinical Trial

Official title:

Biomarker Stratified CaboZantinib (NSC#761968) and NivOlumab (NSC#748726) (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants With Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05136196
• Other study ID #: NCI-2021-12653
• Secondary ID: NCI-2021-12653S2
• Status: Recruiting
• Phase: Phase 2
• Start date: December 6, 2022
• Est. completion date: September 1, 2024

Study information

• Verified date: January 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are "tumor mutational burden" and "tumor inflammation signature." Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of molecular characterization based on tumor mutation burden (TMB) for participant stratification, as assessed by the proportion of participants with less than or equal to a 21-day turnaround time for biopsy results in Stage I of the study.

II. To evaluate the feasibility of molecular characterization based on TMB and gene expression profiling (GEP) (for Tumor Inflammation Score [TIS]) for stratification as assessed by the proportion of participants with less than or equal to a 21-day turnaround time for biopsy results in the overall study (Stage I and Stage II).

III. To evaluate the efficacy by overall response rate (ORR - defined as confirmed and unconfirmed partial responses plus complete responses) of cabozantinib S-malate (cabozantinib) plus nivolumab in each disease cohort, both across and within tumor biomarker subgroups.

SECONDARY OBJECTIVES:

I. To assess the difference in ORR in each disease cohort between tumor marker subgroups separately for each disease cohort.

II. To assess safety and tolerability of this treatment in these populations. III. To estimate disease control rate (DCR) in participants receiving cabozantinib plus nivolumab in each disease cohort, stratified by tumor biomarkers.

IV. To estimate progression-free survival (PFS) in participants receiving cabozantinib plus nivolumab in each disease cohort, stratified by tumor biomarkers.

V. To estimate overall survival (OS) in participants receiving cabozantinib plus nivolumab in each disease cohort, stratified by tumor biomarkers.

VI. To assess the proportion of patients with assay failure, and the time from the date of tissue collection to molecular group determination at the end of Stage I.

ADDITIONAL OBJECTIVE:

I. To identify candidate biomarkers predictive of response and toxicity to the cabozantinib and nivolumab combination.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle and cabozantinib orally (PO) daily. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans and collection of blood samples throughout the trial. Patients undergo a tumor biopsy during screening and optionally during follow-up.

After completion of the study treatment, patients are followed for up to 3 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• STEP 1 - SPECIMEN SUBMISSION

• Participants must have histologically confirmed melanoma that is stage III or IV, unresectable, recurrent, or metastatic non-uveal melanoma OR Participants must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) that is either locally recurrent and non-amendable to curative therapy (e.g., radiation, surgery) or metastatic. The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible

• Note: For participants with primary oropharyngeal cancer, human papillomavirus (HPV) or p16 status must be known prior to step 1 registration

• Participants must have disease presentation consistent with measurable disease. Note:

Current disease measurements will not be required until step 2 registration

• Participants must have had documented progression within 12 weeks after the last dose of PD-1 checkpoint inhibition-based therapy. Participants must have been receiving checkpoint inhibition for a minimum of 6 weeks. Participants who recur during adjuvant anti-PD1 treatment or within 12 weeks of completion of adjuvant anti-PD1 treatment are eligible if they have measurable disease and are considered unresectable

• Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test within 6 months prior to step 1 registration

• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to step 1 registration

• Participants with a history of hepatitis C virus (HCV) infection must have no detectable viral load within 28 days prior to step 1 registration

• Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV as mentioned above)

• Participants must not have known history of congenital long QT syndrome and must not have experienced unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke (transient ischemic attack [TIA] or other ischemic event) within 90 days prior to Step 1 registration

• Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days prior to step 1 registration, unless clinically stable with ongoing medical management

• Participants must have recovered to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 toxicities related to any prior treatments, unless adverse events are deemed clinically nonsignificant by the treating investigator or stable on supportive therapy

• Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the mucosal surfaces of the head and neck, with the additional following criteria:

• If the primary radiation is combined with chemotherapy, a minimum of 16 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration. If the radiation is given alone, a minimum of 8 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration

• Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) with the exception of central nervous system (CNS) radiation and must be completed at least 4 weeks prior to step 1 registration

• Treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation

• Participants must not have received prior treatment with anti-VEGF therapies for any reason

• Participants must be >= 18 years of age

• Participants must have a Zubrod Performance Status 0 or 1

• Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better to be eligible for this trial

• Participants must not have any known significant organ disfunction that, in the opinion of the treating investigator, may impact suitability for receiving combination nivolumab/cabozantinib treatment

• Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules

• Participants must not have malabsorption syndrome

• Participants must not have active autoimmune disease requiring systemic steroids (equivalent of > 10mg of prednisone) or other immune suppression. Exceptions:

• Type 1 diabetes mellitus

• Endocrinopathy only requiring hormone replacement

• Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment

• Conditions not expected to recur in the absence of an external trigger

• Participants must not have received an organ allograft

• Participants must not have a history of hemoptysis (defined as >= 1/2 tsp of bright red blood per day) or tumor bleeding within 90 days prior to step 1 registration

• Participants must not have any of the following criteria due to the possibility of increased risk for tumor bleeding with cabozantinib therapy:

• Prior carotid bleeding

• Tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies

• Central (e.g., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies

• Any prior history of bleeding related to the current head and neck cancer

• History of gross hemoptysis (bright red blood of 1/2 teaspoon or more per episode of coughing) within 3 months

• Participants must not require concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)

• Participants must not require anticoagulants except for the following:

• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).

• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors, rivaroxaban, edoxaban, or apixaban in participants without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to step 1 registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor

• Participants must not have evidence of preexisting uncontrolled hypertension 28 days prior to step 1 registration as documented by baseline blood pressure reading with systolic blood pressure >= 150 mmHg and/or diastolic blood pressure >= 90 mmHg. Participants on antihypertensive therapies with controlled blood pressure are eligible

• Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen

• Participants must not be pregnant or nursing due to the known safety profiles of the drugs in this study. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential. In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion and vasectomy with testing showing no sperm in the semen

• Have an adequate archival tissue specimen verified by the local pathologist and documented on the Pathology Review Form from a procedure obtained after the development of resistance to anti-PD-1/L1 therapy. Archival tissue must consist of tumor block or at least 1 H&E-stained 4-5 micron slide and 20 freshly cut serially sectioned and numbered 4-5 micron unstained, uncharged slides OR

Be willing to undergo research biopsy AND have tumor accessible for biopsy based on the following criteria:

• Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies can be obtained incidentally to a clinically necessary procedure and NOT for the sole purpose of the clinical trial

• Acceptable biopsy procedures are:

• Percutaneous biopsy with local anesthetic and/or sedation with an expected risk of severe complications < 2%

• Direct transoral biopsy (with or without local anesthetic and/or sedation) with an expected risk of severe complications < 2%

• Excisional cutaneous biopsy with local anesthetic and/or sedation with an expected risk of severe complications < 2%

• Biopsy with removal of additional tumor tissue during a medically necessary mediastinoscopy, laparoscopy, gastrointestinal endoscopy, bronchoscopy or craniotomy. No open surgical, laparoscopic or endoscopic procedure should be performed solely to obtain a biopsy for this protocol

• Removal of additional tumor tissue during a medically necessary surgical procedure

• Participants must submit whole blood for germline genomic analysis

• Participants must have been offered the opportunity to participate in specimen banking

• Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

• Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)

• STEP 2 TREATMENT REGISTRATION

• Note: No tests or exams are required to be repeated for Step 2 registration (Treatment). However, participants who are known to have a change in eligibility status after Step 1 registration are not eligible for Step 2 registration

• Participants must have been eligible for step 1 registration continue to meet eligibility for step 1 registration prior to step 2 registration.

• Participants must have had their tumor tissue submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System prior to step 2 registration

• Participants registered during stage II of the protocol must have received assignment to an open cohort from the SWOG Statistics and Data Management Center based on their biomarker screening profile (not applicable for patients registered during stage I of the protocol)

• Participants must have measurable disease. All measurable disease must be assessed within 28 days prior to step 2 registration. All non-measurable disease must be assessed within 42 days prior to step 2 registration. Note: All disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)

• For melanoma participants, CT chest, abdomen and pelvis must be obtained. For HNSCC participants, CT neck and chest must be obtained. Further imaging (i.e., MR brain, CT abdomen/pelvis or extremities, bone scan) will be performed as deemed appropriate by the treating physician

• Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy

• Participants must not have experienced any significant health changes that, in the opinion of the treating investigator, may impact continued suitability for receiving combination nivolumab/cabozantinib treatment

• Participants with treated brain metastases must have discontinued steroid treatment at least 14 days prior to step 2 registration

• Participants must not have received investigational agents or monoclonal antibodies (except Food and Drug Administration [FDA] approved supportive care antibodies, such as denosumab) within 28 days prior to step 2 registration

• Participants must not have received surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to step 2 registration.

• Participants must not have received administration of a live, attenuated vaccine within 30 days prior to step 2 registration. Note: Participants may have received a messenger ribonucleic acid (mRNA) or viral vector-based coronavirus disease 2019 (COVID-19) vaccine within 30 days prior to step 2 registration

• Participants must not have received administration of any strong CYP3A4 inducers, such as but not limited to rifampin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John's wort, within 14 days prior to step 2 registration

• Participants must not have received administration of any strong CYP3A4 inhibitors, such as but not limited to clarithromycin, itraconazole, ketoconazole, grapefruit juice, indinavir, nelfinavir, ritonavir, nefazodone, saquinavir, and telithromycin, within 5 times the half-life of the CYP3A inhibitor prior to step 2 registration

• Participants must have a history and physical examination performed within 28 days prior to step 2 registration

• Leukocytes >= 3,000/uL (within 28 days prior to step 2 registration)

• Absolute neutrophil count >= 1,500/uL (within 28 days prior to step 2 registration)

• Platelets >= 100,000/uL (within 28 days prior to step 2 registration)

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) or =< 3 x ULN for participants with Gilbert's disease (within 28 days prior to step 2 registration)

• Aspartate aminotransferase (AST) =< 3 x institutional ULN (within 28 days prior to step 2 registration)

• Alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to step 2 registration)

• Urinalysis: For baseline value (no required value for eligibility)

• Measured (OR calculated) creatinine clearance >= 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to step 2 registration

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Clinical Stage III Cutaneous Melanoma AJCC v8
• Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Head and Neck Squamous Cell Carcinoma
• Hypopharyngeal Squamous Cell Carcinoma
• Laryngeal Neoplasms
• Laryngeal Squamous Cell Carcinoma
• Lip and Oral Cavity Squamous Cell Carcinoma
• Lip Neoplasms
• Melanoma
• Mouth Neoplasms
• Oropharyngeal Neoplasms
• Oropharyngeal Squamous Cell Carcinoma
• Skin Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Stage III Hypopharyngeal Carcinoma AJCC v8
• Stage III Laryngeal Cancer AJCC v8
• Stage III Lip and Oral Cavity Cancer AJCC v8
• Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8
• Stage IV Hypopharyngeal Carcinoma AJCC v8
• Stage IV Laryngeal Cancer AJCC v8
• Stage IV Lip and Oral Cavity Cancer AJCC v8
• Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Intervention

Procedure:
• Biopsy
Undergo tumor biopsies
• Biospecimen Collection
Undergo collection of blood samples

Drug:
• Cabozantinib S-malate
Given PO

Procedure:
• Computed Tomography
Undergo CT scans
• Magnetic Resonance Imaging
Undergo MRI scans

Biological:
• Nivolumab
Given IV

Locations

Country	Name	City	State
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Inova Alexandria Hospital	Alexandria	Virginia
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Rocky Mountain Regional VA Medical Center	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Trinity Health Medical Center - Brighton	Brighton	Michigan
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Trinity Health Medical Center - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Chelsea Hospital	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Carle at The Riverfront	Danville	Illinois
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Premier Blood and Cancer Center	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Inova Fair Oaks Hospital	Fairfax	Virginia
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Miami Valley Cancer Care and Infusion	Greenville	Ohio
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	Ascension Borgess Cancer Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Centra Alan B Pearson Regional Cancer Center	Lynchburg	Virginia
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Alphonsus Cancer Care Center-Ontario	Ontario	Oregon
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kootenai Clinic Cancer Services - Sandpoint	Sandpoint	Idaho
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Essentia Health Saint Mary's Hospital - Superior	Superior	Wisconsin
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Carle Cancer Center	Urbana	Illinois
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	University of Michigan Health - West	Wyoming	Michigan
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Additional markers of response or resistance	Explore additional markers of response or resistance through hypothesis generating analysis.	Up to 2 years
Primary	Biomarker results turnaround time	A biomarker turnaround time estimate of at least 75% within 21 days will be considered successful with respect to feasibility.	Time-period between date of tissue submission by the site to central repository and date the site was sent notification of participant molecular group determination, assessed within 21 days
Primary	Objective response rate	Confirmed and unconfirmed complete and partial responses) in molecular subgroups. Assume each biomarker level is associated with an odds-ratio of approximately 3.1 (for example, corresponding to a difference in response rate of 5 percent to 14 percent from Lo/Lo to Lo/Hi or Hi/Lo). A one-sided .10 level test for trend using (0,1,2) coding above with logistic regression has a power of 80 percent. We will also consider biomarker trend analysis adjusting for disease types. We will also conduct disease-by-biomarker interaction tests; however, there will be limited power even to detect relatively large interaction parameters.	At the end of stage I
Secondary	Rate and profile of >= grade 3 treatment-related adverse events	Per Common Terminology Criteria for Adverse Events 5.0. With respect to overall disease group, 60 participants are sufficient to estimate the probability of a particular toxicity to within +/- 13 percent. Any toxicity occurring with at least a 5 percent probability is likely to be seen at least once (95 percent chance).	Up to 2 years
Secondary	Disease control rate	Will be estimated using the method of Kaplan-Meier.	Up to 2 years
Secondary	Progression-free survival	Will be estimated using the method of Kaplan-Meier.	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years
Secondary	Overall survival	Will be estimated using the method of Kaplan-Meier.	From date of registration to date of death due to any cause, assessed up to 2 years
Secondary	Turnaround time for the Tumor Inflammation Score in stage II		Assessed within 21 days