Regorafenib, with Cetuximab or Panitumumab, for the Treatment of Unresectable, Locally Advanced, or Metastatic Colorectal Cancer

Active:	No
Cancer Type:	Colon/Rectal Cancer Unknown Primary	NCT ID:	NCT04117945
Trial Phases:	Phase II	Protocol IDs:	ACCRU-GI-1809 (primary) NCI-2019-06518
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Academic and Community Cancer Research United
NCI Full Details:	http://clinicaltrials.gov/show/NCT04117945

Summary

This phase II trial investigates how well regorafenib and anti-EGFR therapy (cetuximab or panitumumab) works for the treatment of patients with colorectal cancer that cannot be removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic). Regorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab or panitumumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as irinotecan, 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. The purpose of this research study is to compare the effects, good and/or bad, of taking regorafenib follow by cetuximab or panitumumab, to those that receive cetuximab or panitumumab before regorafenib.

Objectives

PRIMARY OBJECTIVE:
I. To compare the overall survival between evaluable patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib.

SECONDARY OBJECTIVES:
I. To compare the first progression free survival (PFS1) of patients between evaluable patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib.
II. To compare the second progression free survival (PFS2) of patients between evaluable patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib.
III. To compare the sequential treatment progression free survival (stPFS) of patients between evaluable patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib.
IV. To assess the frequency and severity of adverse events between evaluable patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib.
V. To compare the objective response rate (ORR), while on initial treatment, between evaluable patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib.
VI. To compare the objective response rate (ORR), while on sequential treatment, between evaluable patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody prior to regorafenib.

CORRELATIVE RESEARCH OBJECTIVES:
I. To assess plasma pharmacodynamics biomarkers of response and resistance to therapy.
II. To explore any correlation between tissue and blood based biomarkers and clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive regorafenib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Per the treating physician's discretion, patients who experience disease progression may initiate a treatment regimen consisting of cetuximab or panitumumab intravenously (IV) over 30-90 minutes on days 1 and 15. Patients may also receive irinotecan IV on days 1 and 15 as determined by the study doctor. Cycles repeat every 28 days until disease progression or unacceptable toxicity.

ARM B: Patients receive cetuximab or panitumumab IV over 30-90 minutes on days 1 and 15. Patients may also receive irinotecan IV on days 1 and 15 as determined by the study doctor. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Per the treating physician's discretion, patients who experience disease progression may initiate a treatment regimen consisting of regorafenib PO QD on days 1-21. Cycles repeat every 28 days until disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 3 months for up to 3 years after randomization.

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.