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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

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.

Condition or disease Intervention/treatment Phase
Rectal Cancer Drug: Capecitabine Radiation: Radiation therapy Drug: mFOLFOX6 Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : October 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Neoadjuvant Treatment
All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment
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

Primary Outcome Measures :
  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

Secondary Outcome Measures :
  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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03921684

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Contact: Baruch Brenner, Prof 972-3-9378002

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Rabin Medical Center, Beilinson Hospital Recruiting
Petach Tikva, Israel
Contact: Baruch Brenner, Prof         
Principal Investigator: Baruch Brenner, Prof         
Sponsors and Collaborators
Baruch Brenner
Bristol-Myers Squibb
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Principal Investigator: Baruch Brenner, Prof Rabin Medical Center
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Responsible Party: Baruch Brenner, Director of the Oncology Division and the Davidoff Cancer Center, Rabin Medical Center Identifier: NCT03921684    
Other Study ID Numbers: CA209-8M4
First Posted: April 19, 2019    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Baruch Brenner, Rabin Medical Center:
rectal cancer
Anti-PD-1 antibody
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological