NCT02948348

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
90

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Oct 2016

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 8, 2016

Completed
23 days until next milestone

Study Start

First participant enrolled

October 1, 2016

Completed
27 days until next milestone

First Posted

Study publicly available on registry

October 28, 2016

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2021

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2022

Completed
Last Updated

September 16, 2021

Status Verified

September 1, 2021

Enrollment Period

5.2 years

First QC Date

September 8, 2016

Last Update Submit

September 7, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

  • Pathological complete response

    Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging

    1 year

Secondary Outcomes (9)

  • Objective response rate

    1 year

  • Recurrence pattern (local or distant)

    1 year

  • Disease-free survival (DFS)

    5years

  • Overall survival (OS)

    5years

  • Incidence of adverse events (AEs)

    1 year

  • +4 more secondary outcomes

Study Arms (1)

Nivolumab & Ipilimumab(Only Cohort D)

EXPERIMENTAL

chemoradiotherapy with capecitabine+ Nivolumab + Ipilimumab(Only Cohort D) + surgical therapy

Drug: NivolumabDrug: Ipilimumab

Interventions

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).

Also known as: Opdivo, Chemoradiotherapy with capecitabine, Surgical therapy
Nivolumab & Ipilimumab(Only Cohort D)

For only Cohort D,1 mg/kg at six-week intervals

Also known as: Yervoy
Nivolumab & Ipilimumab(Only Cohort D)

Eligibility Criteria

Age20 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • (A. Phase Ib and Cohorts A and D only)
  • A1. Rectal cancer patients who have not undergone treatment for pre-CRT tumors situated 12 cm or less from the lower edge of the AV.
  • A2. The primary rectal lesion is histopathologically diagnosed as adenocarcinoma.
  • A3. Pre-CRT clinical stage is clinical T3-4 N-any M0.
  • A4. Macroscopic radical resection is deemed possible on pre-CRT image diagnosis.
  • A5. Aged between 20 and 80 years at the time of enrollment.
  • (B. Cohort B only)
  • B1. Clinically diagnosed with local recurrence after rectal surgery.
  • B2. The main site of recurrence is limited to the pelvis by pre-CRT imaging diagnosis.
  • B3. Macroscopic radical resection is deemed possible on pre-CRT imaging diagnosis.
  • B4. Aged between 20 and 75 years at the time of enrollment.
  • (C. Cohort C only)
  • C1. Rectal cancer patients who have not undergone pretreatment for a pre-CRT tumor which is 12 cm or less from the lower AV.
  • C2. The primary rectal lesion is histopathologically diagnosed as adenocarcinoma.
  • C3. The pre-CRT clinical stage is clinical T3-4 N-any M1a (liver) M1a (lungs).
  • +11 more criteria

You may not qualify if:

  • Patients diagnosed with active double cancer (synchronous double cancer and double cancer with disease-free period within five years from enrollment).
  • However, lesions equivalent to intraepithelial or mucosal carcinoma deemed cured by localized treatment are not classified as active double cancer.
  • Patients with a history of pelvic irradiation prior to this rectal cancer treatment.
  • Patients who have not given consent through the informed consent form.
  • Patients deemed by the investigator to be ineligible for the trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

RECRUITING

Hokkaido University

Sapporo, Hokkaido, Japan

RECRUITING

Osaka National Hospital

Osaka, Japan

RECRUITING

Related Publications (1)

  • Tsukada Y, Bando H, Inamori K, Wakabayashi M, Togashi Y, Koyama S, Kotani D, Yuki S, Komatsu Y, Homma S, Taketomi A, Uemura M, Kato T, Fukui M, Nakamura N, Kojima M, Kawachi H, Kirsch R, Yoshida T, Sato A, Nishikawa H, Ito M, Yoshino T. Three-year outcomes of preoperative chemoradiotherapy plus nivolumab in microsatellite stable and microsatellite instability-high locally advanced rectal cancer. Br J Cancer. 2024 Jul;131(2):283-289. doi: 10.1038/s41416-024-02730-7. Epub 2024 Jun 4.

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

NivolumabChemoradiotherapyCapecitabineIpilimumab

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCombined Modality TherapyTherapeuticsDrug TherapyRadiotherapyDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Study Officials

  • Takayuki Yoshino, Dr

    Gastrointestinal Oncology Division National Cancer Center Hospital East

    STUDY CHAIR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Director of Gastrointestinal Oncology Division

Study Record Dates

First Submitted

September 8, 2016

First Posted

October 28, 2016

Study Start

October 1, 2016

Primary Completion

December 1, 2021

Study Completion

August 1, 2022

Last Updated

September 16, 2021

Record last verified: 2021-09

Locations