Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

• ClinicalTrials.gov Identifier: NCT03921684
• Recruitment Status: Recruiting
• First Posted: April 19, 2019
• Last Update Posted: April 19, 2019
• Sponsor: Baruch Brenner
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Baruch Brenner, Rabin Medical Center

Tracking Information

• First Submitted Date: April 14, 2019
• First Posted Date: April 19, 2019
• Last Update Posted Date: April 19, 2019
• Estimated Study Start Date: April 2019
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2019)

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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 17, 2019)

• Disease Free Survival (DFS) [ Time Frame: 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 ]
  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
• Overall Survival (OS) [ Time Frame: The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months ]
  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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients
• Official Title: Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rectal Cancer

Intervention

• Drug: Capecitabine
  Capecitabine 825 mg/m2 orally twice-daily, 5 days a week for a total of 28 days, given with radiation therapy
  Other Name: 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 Name: Opdivo

Study Arms

Experimental: Neoadjuvant Treatment

All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment

Interventions:

• Drug: Capecitabine
• Radiation: Radiation therapy
• Drug: mFOLFOX6
• Drug: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 17, 2019): 29
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2025
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Baruch Brenner, Prof; 972-3-9378002; brennerb@clalit.org.il

• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT03921684
• Other Study ID Numbers: CA209-8M4
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Baruch Brenner, Rabin Medical Center
• Study Sponsor: Baruch Brenner
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Baruch Brenner, Prof; Rabin Medical Center

• PRS Account: Rabin Medical Center
• Verification Date: April 2019