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Study to Nivolumab Following Preoperative Chemoradiotherapy

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. Read our disclaimer for details. Identifier: NCT02948348
Recruitment Status : Unknown
Verified February 2017 by Takayuki Yoshino, National Cancer Center Hospital East.
Recruitment status was:  Recruiting
First Posted : October 28, 2016
Last Update Posted : February 16, 2017
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Takayuki Yoshino, National Cancer Center Hospital East

Brief Summary:
This is a phase Ib/II, open-label, single-arm, multicenter study to investigate the safety, efficacy, and proof of concept (POC) of monotherapy with nivolumab, an anti-PD-1 antibody drug, as a sequential therapy following chemoradiotherapy (CRT) with capecitabine and subsequent surgical therapy in patients with locally advanced resectable rectal cancer.

Condition or disease Intervention/treatment Phase
Cancer of Rectum Drug: Nivolumab Phase 1 Phase 2

Detailed Description:

[Phase Ib]

After preoperative CRT, to sequentially administer nivolumab in combination for patients with locally advanced resectable rectal cancer. To evaluate the safety of nivolumab in sequential combination therapy, the onset of dose-limiting toxicity (DLT) and the safety of subsequent surgical therapy, and to decide on a recommended dose (RD) for the phase II part.

[Phase II]

To evaluate the efficacy and safety when nivolumab is sequentially administered in combination at the RD determined in the phase Ib part, following preoperative CRT in patients with locally advanced resectable rectal cancer and to identify biomarkers related to the therapeutic response. To also evaluate the safety of surgical therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Multicenter Study to Investigate the Safety, Efficacy and Proof of Concept (POC) of Nivolumab Monotherapy as a Sequential Therapy Following Preoperative Chemoradiotherapy Patients With Locally Advanced Resectable Rectal Cancer
Study Start Date : October 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Nivolumab
chemoradiotherapy with capecitabine+ Nivolumab + surgical therapy
Drug: Nivolumab
Capecitabine:Dose of 1650mg/m2,14days, Radiation:45Gy/25 fractions, Nivolumab :240mg on day1 of each cycle, Surgical therapy:The resection (LAR), intersphincteric resection (ISR), or abdominoperineal resection (APR).
Other Names:
  • Opdivo
  • Chemoradiotherapy with capecitabine
  • Surgical therapy

Primary Outcome Measures :
  1. Pathological complete response [ Time Frame: 1 year ]
    Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging

Secondary Outcome Measures :
  1. Objective response rate [ Time Frame: 1 year ]
  2. Mode of recurrence [ Time Frame: 1 year ]
    Evaluation Criteria In Solid Tumors (RECIST)

  3. Disease-free survival (DFS) [ Time Frame: 5years ]
  4. Overall survival (OS) [ Time Frame: 5years ]
  5. Incidence of adverse events (AEs) [ Time Frame: 1 year ]
  6. Rate of completing the protocol therapy [ Time Frame: 1 year ]
  7. Rate of radical resection [ Time Frame: 1 year ]
  8. Safety evaluation [ Time Frame: 5years ]
    Safety will be evaluated with CTCAE v4.0

  9. macroscopic evaluation of (rectal cancer) resected specimen [ Time Frame: 1 year ]

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:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients who personally provided written consent for participation in the study
  • Treatment-naive patients with rectal cancer, in whom the inferior margin of the tumor was at a distance of 12 cm or less from the AV before CRT
  • Primary rectal cancer histopathologically confirmed to be adenocarcinoma
  • Clinical stage of T3,and T4 ,N any,M0,before CRT
  • Macroscopic radical resection could be feasible, based on diagnostic imaging before CRT
  • Patients with the ECOG performance status of 0 or 1 at the time of enrollment
  • CRT meeting the following conditions has been administered:

Radiation at a dose of 45Gy 25 fractions to the pelvic cavity and boost radiation at a dose of 5.4Gy 3 fractions to the primary lesion

  • Capecitabine was started at a dose of 1650 mg/m2 and orally administered in combination with radiation during a period equivalent to the half of 28 fractions , irrespective of a dose reduction.
  • The last day of CRT is defined as the last day of radiotherapy. Oral administration of capecitabine is completed at the same time as the completion of radiation.
  • Patients with CRT associated AEs that recovered to grade 1 based on the CTCAE ver. 4.0, with regard to all items within 14 days after the end of CRT who are anticipated to be able to receive nivolumab.
  • Patients without distant metastasis on the imaging test at the end of CRT
  • Women of childbearing potential who consent to practicing contraception during the period from giving informed consent to at least 23 weeks after the last dose of therapy
  • Male patients who consent to practicing contraception during the period from giving informed consent to at least 31 weeks after the last dose of the study drug

Exclusion criteria:

  • Active multiple cancers However, lesions equivalent to cancer in situ or intramucosal cancer determined to have been cured by local treatment are not included in active multiple cancers.
  • Patients with recurrent rectal cancer
  • Patients with a history of pelvic radiation
  • Patients with a history of inflammatory bowel disease
  • Patients with a history of pneumonitis or interstitial lung disease
  • Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease
  • Patients requiring treatment with systemic corticosteroids or immunosuppressants or who have received these treatments within 14 days before enrollment in the study
  • Patients with a history of thyroid dysfunction
  • Patients with a history or finding of cardiovascular risk falling into any of the following:
  • Patients with a left ventricular ejection rate below 50percent based on ejection fraction
  • Patients with a history or finding of clinically significant, poorly controlled arrhythmia; exception: patients with well-controlled atrial fibrillation for more than 30 days before enrollment may be enrolled.
  • Patients with a history of acute coronary syndrome , coronary angioplasty, or stent placement within 6 months before enrollment
  • Patients with a history or finding of class II or more severe congestive heart failure according to the New York Heart Association Functional Classification
  • Patients with treatment-resistant hypertension ・Patients wearing an implantable cardioverter defibrillator or permanent pacemaker
  • Patients with poorly controlled diabetes mellitus or other diseases possibly interfering with toxicity evaluation
  • Patients who are positive for any of the following: HIV1 antibody, HIV2 antibody, HTLV1 antibody, HBs antigen, or HCV antibody test
  • Patients who are pregnant or lactating or who may be pregnant
  • Patients with significant unstable mental diseases or other medical diseases that may interfere with the safety of the subjects, obtaining informed consent, or compliance with the procedures for the clinical study

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): NCT02948348

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Contact: Hideaki Bando, Dr +81-4-7133-1111 ext 91114
Contact: Yuichiro Tsukada, Dr +81-4-7133-1111 ext 92331

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National Cancer Center Hospital East Recruiting
Kashiwa, Chiba, Japan
Sponsors and Collaborators
Takayuki Yoshino
Ono Pharmaceutical Co. Ltd
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Study Chair: Takayuki Yoshino, Dr Gastrointestinal Oncology Division National Cancer Center Hospital East
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Responsible Party: Takayuki Yoshino, Director of Gastrointestinal Oncology Division, National Cancer Center Hospital East Identifier: NCT02948348    
Other Study ID Numbers: EPOC1504
First Posted: October 28, 2016    Key Record Dates
Last Update Posted: February 16, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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