Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer

This is a phase II, prospective, open label, one-center study for evaluation of the addition of nivolumab to the chemotherapy phase of the neoadjuvant treatment for locally advanced rectal cancer patients. Subjects must have received no prior treatment for rectal cancer (chemotherapy, radiotherapy or surgery) and no prior treatment with checkpoint inhibitors.

Eligible subjects will receive chemoradiation for a period of 5 weeks, 6 cycles of chemo-immunotherapy (mFOLFOX6 + nivolumab) for a period of 12 weeks, once every 2 weeks, and will undergo surgery after 4 weeks.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Capecitabine; Radiation: Radiation therapy; Drug: mFOLFOX6; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel
    • Recruiting
    • Rabin Medical Center, Beilinson Hospital
    • Principal Investigator: Baruch Brenner, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written IRB approved informed consent
• Age ≥ 18 years
• ECOG PS 0-1
• Subjects with histologically confirmed primary (non-recurrent) locally advanced rectal adenocarcinoma
• Stage T3-4 N0 or TX N+ according to baseline rectal EUS and PET-CT
• Patients who are planned for neoadjuvant chemoradiation and are surgical candidates
• No prior chemotherapy, radiotherapy or surgery for rectal cancer
• No prior radiotherapy to the pelvis, for any reason
• Presence of adequate contraception in fertile patients
• Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug
• Women must not be breastfeeding
• Ability to swallow tablets
• No previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin

Exclusion Criteria:

• Active autoimmune disease. [Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll]
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant Treatment; All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment

Drug: Capecitabine; Capecitabine 825 mg/m2 orally twice-daily, 5 days a week for a total of 28 days, given with radiation therapy; Other Names: Xeloda; Radiation: Radiation therapy; 1.8 Gy/day, 5 days a week for a total of 28 days, given with Capecitabine; Drug: mFOLFOX6; oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and fluorouracil 400 mg/m2 IV, fluorouracil 2400 mg/m2 IV (a 46 hrs CI), day 1 of each treatment cycle, every 2 weeks, given with nivolumab; Drug: Nivolumab; Nivolumab 240mg IV, day 1 of each treatment cycle, every two weeks, given with mFOLFOX6; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete response (pCR) rate	pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)	Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months
Incidence of Treatment-Emergent Adverse Events (Safety)	Treatment-emergent AEs will be graded according to NCI CTCAE v4.0, vital signs and clinical laboratory	Time from screening until the end of study drug administration, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	DFS will be censored for patients who are alive and free of progression at the time of last follow-up. DFS rate will be estimated using the Kaplan-Meier method	Time from the first day of treatment to the first event of: loco-regional failure, metastatic recurrence, the appearance of a secondary colorectal cancer or death from any cause, assessed up to 42 months
Overall Survival (OS)	Patients who are still alive when last traced will be censored at the date of last follow-up. OS rate will be estimated using the Kaplan-Meier method	The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months

Collaborators and Investigators

• Sponsor: Baruch Brenner
• Collaborators: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2019
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: April 14, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 19, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Chemoradiation; Nivolumab; rectal cancer; Anti-PD-1 antibody; mFOLFOX6
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Capecitabine; Nivolumab
• Other Study ID Numbers: CA209-8M4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No