Panitumumab, Regorafenib, or TAS-102, in Treating Patients With Metastatic and/or Unresectable RAS Wild-Type Colorectal Cancer

NCT03992456 | Active Not Recruiting Phase 2 Results DMC FDA Drug FDA Device

• 3 other identifiers: ACCRU-GI-1623NCI-2019-03306P30CA015083
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 18

Brief Summary

This phase II trial studies how well retreatment with panitumumab works compared to standard of care regorafenib or trifluridine and tipiracil hydrochloride (TAS-102) in treating patients with colorectal cancer that is negative for RAS wild-type colorectal cancer has spread to other places in the body (metastatic), and/or cannot be removed by surgery (unresectable), and is negative for resistance mutations in blood. Treatment with panitumumab may interfere with the ability of tumor cells to grow and spread. Some tumors need growth factors to keep growing. Growth factor antagonists, such as regorafenib, may interfere with the growth factor and stop the tumor from growing. Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving panitumumab may work better in treating patients with colorectal cancer than with the usual treatment of regorafenib or TAS-102.

Conditions

Metastatic Colon Adenocarcinoma; Metastatic Colorectal Carcinoma; Metastatic Rectal Adenocarcinoma; Stage III Colon Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage III Rectal Cancer AJCC v8; Stage IIIA Colon Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIA Rectal Cancer AJCC v8; Stage IIIB Colon Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIB Rectal Cancer AJCC v8; Stage IIIC Colon Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IIIC Rectal Cancer AJCC v8; Stage IV Colon Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Rectal Cancer AJCC v8; Stage IVA Colon Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVA Rectal Cancer AJCC v8; Stage IVB Colon Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVB Rectal Cancer AJCC v8; Stage IVC Colon Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Stage IVC Rectal Cancer AJCC v8; Unresectable Colon Adenocarcinoma; Unresectable Colorectal Carcinoma; Unresectable Rectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS is defined as the Time from randomization to death from any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier. Overall survival will be compared between the 2 treatment arms using the un-stratified log-rank test will be used.

  2 years

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  1 year

• Overall Response Rate (ORR)

  2 years

• Clinical Benefit Rate

  4 months

• Incidence of Adverse Events

  2 years

• Patient-reported Quality of Life

  2 years

Other Outcomes (3)

• Cell Free Tumor Deoxyribonucleic Acid (cfDNA)

  Baseline, at restaging, and at disease progression

• Circulating Protein Studies

  Up to 3 years

• Tumor Tissue Studies

  Up to 3 years

Study Arms (2)

Arm A (panitumumab)

EXPERIMENTAL

Patients receive panitumumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Panitumumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm B (regorafenib, trifluridine and tipiracil hydrochloride)

ACTIVE COMPARATOR

Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and 8-12, or regorafenib PO QD on days 1-21, at the discretion of the treating physician. Treatment repeats every 28 days for a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity.

Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Regorafenib; Drug: Trifluridine and Tipiracil Hydrochloride

Interventions

Panitumumab BIOLOGICAL

Given IV

Also known as: ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, E7.6.3, Human IgG2K Monoclonal Antibody, MoAb ABX-EGF, MoAb E7.6.3, Monoclonal Antibody ABX-EGF, Monoclonal Antibody E7.6.3, Vectibix

Arm A (panitumumab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (panitumumab); Arm B (regorafenib, trifluridine and tipiracil hydrochloride)

Questionnaire Administration OTHER

Ancillary studies

Arm A (panitumumab); Arm B (regorafenib, trifluridine and tipiracil hydrochloride)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Regorafenib Anhydrous

Arm B (regorafenib, trifluridine and tipiracil hydrochloride)

Trifluridine and Tipiracil Hydrochloride DRUG

Given PO

Also known as: Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102

Arm B (regorafenib, trifluridine and tipiracil hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Most recent Guardant360 blood collection date =\< 90 days prior to randomization.
• NOTE: If a patient does not have Guardant360 test results available, enrollment in ACCRU\_GI-1611 (COLOMATE) is strongly encouraged.
• Greater than 90 days has elapsed between the most recent treatment with an anti-epidermal growth factor receptor gene (EGFR) therapy (cetuximab or panitumumab) and blood collection for Guardant360 assay.
• Age \>= 18 years.
• Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic and/ or unresectable.
• Documented wild-type in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146) and in BRAF codon 600, based on tumor tissue taken from primary or metastatic site prior to receipt of anti EGFR therapy.
• Progression, intolerance, or contraindication to:
• A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine)
• Oxaliplatin
• Irinotecan
• An anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, or aflibercept).
• If the tumor has deficient mismatch repair proteins (dMMR) or is microsatellite instability (MSI)-high based on tumor tissue testing, an anti-programmed death (PD)-1 monoclonal antibody (including but not limited to nivolumab or pembrolizumab).
• Clinical or radiographic progression after treatment with an anti-EGFR monoclonal antibody (cetuximab and/or panitumumab) for at least 3 months (minimum of 6 biweekly treatments or 12 weekly treatments at full or partial dose).
• NOTE: Treatments do not need to be administered consecutively.
• NOTE: Dose reductions or delays are permitted.

You may not qualify if:

• Radiation therapy, hormonal therapy, biologic therapy, experimental therapy, or chemotherapy for cancer \< 21 days prior to randomization.
• Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin).
• Maximum mutant allele frequency (highest allele frequency reported for any gene mutation) (MAF) less than 0.5% by Guardant360 assay.
• Detection of at least one of the following gene mutation(s) or amplification(s) by Guardant360 assay.
• BRAFV600E mutation (mutant allele frequency (MAF) \>= 0.5% or amplification.
• ERBB2 (HER2) amplification.
• KRAS mutation (MAF \>= 0.5%) or amplification.
• MET amplification.
• NRAS mutation (MAF \>= 0.5%) or amplification.
• Prior treatment with both TAS-102 and regorafenib (prior treatment with either TAS-102 or regorafenib is permitted).
• Unable to swallow oral tablets (crushing of study treatment tablets is not allowed).
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. Note: This includes impaired heart function or clinically significant heart disease.
• Not recovered to baseline or Common Terminology for Adverse Events (CTCAE) version (v)5.0 =\< grade 1 from toxicity due to all prior therapies except alopecia, oxaliplatin-related neuropathy, asymptomatic electrolyte abnormalities, and other non-clinically significant adverse events.
• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant women.

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (18)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Aurora Cancer Care-Milwaukee West

Wauwatosa, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms; Rectal Neoplasms

Interventions

Panitumumab; regorafenib; Trifluridine; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: John Strickler, MD
• Organization: Duke Cancer Institute

john.strickler@duke.edu

(507) 284-2511

Study Officials

• John H Strickler

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: April 24, 2020
• Primary Completion: December 1, 2023
• Study Completion: October 7, 2024
• Last Updated: May 21, 2024
• Results First Posted: May 21, 2024

Record last verified: 2024-04

Locations

US (18)