Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

NCT03921684 | Active Not Recruiting Phase 2

• 1 other identifier: CA209-8M4
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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

Keywords

Nivolumab; Chemoradiation; mFOLFOX6; rectal cancer; Anti-PD-1 antibody

Outcome Measures

Primary Outcomes (3)

• 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

• modified pathological complete response

  We defined a novel primary endpoint, combining pathological complete response (pCR) rate among operated patients and long-term (≥12 months) clinical complete response (cCR) rate for those electing watchful waiting, into a composite endpoint of modified pCR (mpCR) rate.

  Time from start of neoadjuvant treatment until surgical resection in operated patients (pCR) and long-term (≥12 months) clinical complete response (cCR) in unoperated patients, assessed up to 24 months.

Secondary Outcomes (2)

• Disease Free Survival (DFS)

  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)

  The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months

Study Arms (1)

Neoadjuvant Treatment

EXPERIMENTAL

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

Drug: Capecitabine; Radiation: Radiation therapy; Drug: mFOLFOX6; Drug: Nivolumab

Interventions

Capecitabine DRUG

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

Also known as: Xeloda

Neoadjuvant Treatment

Radiation therapy RADIATION

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

Neoadjuvant Treatment

mFOLFOX6 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

Neoadjuvant Treatment

Nivolumab DRUG

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

Also known as: Opdivo

Neoadjuvant Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baruch Brenner: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Rabin Medical Center, Beilinson Hospital

Petah Tikva, Israel

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Radiotherapy; Nivolumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Baruch Brenner, Prof

  Rabin Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head, Department of Oncology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital

Study Record Dates

• First Submitted: April 14, 2019
• First Posted: April 19, 2019
• Study Start: April 10, 2019
• Primary Completion: October 28, 2024
• Study Completion (Estimated): October 1, 2029
• Last Updated: January 5, 2026

Record last verified: 2025-12

Locations

IL (1)