Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

NCT ID: NCT03921684

Last Updated: 2026-01-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-10
• Study Completion Date: 2029-10-31

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.

Patients with cCR will be offered the alternative strategy of WW. Post-study systemic treatment, up to 4 cycles of mFOLFOX6, will be left to the discretion of the treating physician. This will be started 4-8 weeks post-operatively, or immediately after the demonstration of cCR in patients determined to undergo WW.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant Treatment

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

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

Capecitabine 825 mg/m2 orally twice-daily, 5 days a week for a total of 28 days, given with radiation therapy

Radiation therapy

Intervention Type: RADIATION

1.8 Gy/day, 5 days a week for a total of 28 days, given with Capecitabine

mFOLFOX6

Intervention Type: DRUG

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

Nivolumab

Intervention Type: DRUG

Nivolumab 240mg IV, day 1 of each treatment cycle, every two weeks, given with mFOLFOX6

Interventions

Capecitabine

Capecitabine 825 mg/m2 orally twice-daily, 5 days a week for a total of 28 days, given with radiation therapy

Intervention Type: DRUG

Radiation therapy

1.8 Gy/day, 5 days a week for a total of 28 days, given with Capecitabine

Intervention Type: RADIATION

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

Intervention Type: DRUG

Nivolumab

Nivolumab 240mg IV, day 1 of each treatment cycle, every two weeks, given with mFOLFOX6

Intervention Type: DRUG

Other Intervention Names

Xeloda; Opdivo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Baruch Brenner

OTHER

Sponsor Role: lead

Responsible Party

Baruch Brenner

Head, Department of Oncology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Baruch Brenner, Prof

Role: PRINCIPAL_INVESTIGATOR

Rabin Medical Center

Locations

Rabin Medical Center, Beilinson Hospital

Petah Tikva, , Israel

Countries

Israel

Other Identifiers

CA209-8M4

Identifier Type: -

Identifier Source: org_study_id