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Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03921684
Recruitment Status : Recruiting
First Posted : April 19, 2019
Last Update Posted : April 19, 2019
Bristol-Myers Squibb
Information provided by (Responsible Party):
Baruch Brenner, Rabin Medical Center

Tracking Information
First Submitted Date  ICMJE April 14, 2019
First Posted Date  ICMJE April 19, 2019
Last Update Posted Date April 19, 2019
Estimated Study Start Date  ICMJE April 2019
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rectal Cancer
Intervention  ICMJE
  • 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  ICMJE Experimental: Neoadjuvant Treatment
All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment
  • Drug: Capecitabine
  • Radiation: Radiation therapy
  • Drug: mFOLFOX6
  • Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 17, 2019)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2025
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Baruch Brenner, Prof 972-3-9378002
Listed Location Countries  ICMJE Israel
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03921684
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Baruch Brenner, Rabin Medical Center
Study Sponsor  ICMJE Baruch Brenner
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Baruch Brenner, Prof Rabin Medical Center
PRS Account Rabin Medical Center
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP