Veliparib, Pembrolizumab, and Combination Chemotherapy in Treating Patient with Locally Advanced Rectal Cancer

Active:	No
Cancer Type:	Colon/Rectal Cancer Unknown Primary	NCT ID:	NCT02921256
Trial Phases:	Phase II	Protocol IDs:	NRG-GI002 (primary) NCI-2016-00222
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	NRG Oncology
NCI Full Details:	http://clinicaltrials.gov/show/NCT02921256

Summary

This randomized phase II trial studies how well veliparib or pembrolizumab work with combination chemotherapy and radiation therapy in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as modified (m)FOLFOX6 regimen, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving veliparib or pembrolizumab with combination chemotherapy and radiation therapy may kill more tumor cells, make the tumor smaller, and reduce the amount of normal tissue that needs to be removed.

Objectives

PRIMARY OBJECTIVE:
I. To demonstrate an absolute improvement in neoadjuvant rectal cancer (NAR) score for the experimental regimen as compared to concurrently randomized control patients.

SECONDARY OBJECTIVES:
I. To compare overall survival (OS).
II. To compare disease-free survival (DFS).
III. To compare the rate of pathologic complete response (pCR) (nodes and tumor).
IV. To compare the rate of sphincter preservation.

TERTIARY OBJECTIVES:
I. To compare the proportion of patients who have a tumor resection overall, conditional on beginning induction chemotherapy, and conditional on beginning chemoradiotherapy.
II. To compare time from initiation of chemoradiotherapy to surgery in the subset of patients with tumor resection.

EXPLORATORY OBJECTIVES:
I. To estimate the rate of disease progression during chemotherapy (prior to chemoradiation).
II. To compare the rate of clinical complete response rate (cCR).
III. To compare the rate of negative circumferential margin.
IV. To compare the rate of completion of all cycles of neoadjuvant chemotherapy.
V. To compare the rate of completion of full course of chemoradiation.
VI. To compare the toxicity and safety between interventions.
VII. To explore the correlative molecular predictors of response and distant failure.
VIII. To explore the relationship between radiographic findings and pathologic outcomes.

OUTLINE: Patients are sequentially randomized to treatment arms, initially ARM I or ARM II and then later either ARM I or ARM III.

ARM I: Patients receive mFOLFOX6 regimen consisting of oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo radiation therapy (RT) and receive capecitabine orally (PO) twice daily (BID) Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID and veliparib PO BID Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID Monday-Friday for 5 weeks. They also receive pembrolizumab IV over 30 minutes every 3 weeks beginning on day 1 of RT for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

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

**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.