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NCT Number: NCT03921684

Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Rabin Medical Center, Beilinson Hospital

Petah Tikva, Israel

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Capecitabine

Drug

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 therapy

Radiation

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

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

Nivolumab

Drug

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

Other names: Opdivo

Primary outcomes

  1. 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)

  2. 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

  3. modified pathological complete response

    Time frame: 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.

    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.

Secondary outcomes

  1. 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

  2. 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

Sponsors and collaborators

Lead sponsor

Baruch Brenner

Other

Collaborators

  • Bristol-Myers Squibb

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2024
Study completion
2029
First posted
Apr 19, 2019
Registry last updated
Jan 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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