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Cancer of RectumPhase 1/2NCT02948348

Study to Nivolumab Following Preoperative Chemoradiotherapy

A Phase 1/2 study testing Nivolumab and Ipilimumab in people with Cancer of Rectum, run by Takayuki Yoshino at 3 sites in Japan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 20 to 80 years
Conditions the study is for
Cancer of Rectum
What is being tested?
Nivolumab and Ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
3 sitesJapan
Study dates
Oct 2016to Aug 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 26Show fewer
  • 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.
  • 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).
  • C4. Macroscopic curative resection of the primary rectal lesion is deemed possible on pre-CRT imaging diagnosis.
  • C5. A metastatic liver tumor or a metastatic lung tumor has been diagnosed as clinically resectable prior to CRT and during clinical trial enrollment.
  • Common to all cohorts in Phase Ib and Phase II)
  • D1. Patients who have provided consent through a consent form.
  • D2. Patients whose Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is 0 or 1 at the time of enrollment.
  • D3. CRT was administered:
  • D4. Patients whose CRT adverse events have recovered to Grade 1 or lower based on CTCAE ver.4.0. within 14 days after the end of CRT, and are expected to be able to take nivolumab (patient is still eligible even if adverse events are not restored to Grade 1, provided that the blood cell count satisfies the eligibility criteria specified in point D8).
  • D5. Patients with no remote metastases as confirmed by imaging at the end of CRT (testing is allowed from 14 days before the end of CRT to the trial enrollment date).
  • D6. For women who may become pregnant (including patients who are not menstruating due to chemically-induced menopause among other medical reasons), patients who agree to use contraception for at least 23 weeks after the last administration of the investigational drug, starting from the day they provide consent (30 days (ovulation cycle) plus five times the elimination half-life of the investigational drug).
  • D7. For men, patients who agree to use contraception for at least 31 weeks after the last administration of the investigational drug, starting from the day they provide consent (90 days (spermatogenesis cycle) plus five times the elimination half-life of the investigational drug).
  • D8. Patients who have the sufficient organ function at the time of enrollment.

Who cannot join

  • 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.

Trial locations and contacts

3 sites in 1 country.

Hideaki Bando, Dr contact

+81-52-762-6111

voltage_core@east.ncc.go.jp

Yuichiro Tsukada, Dr contact

+81-4-7133-1111 ext. 92331

voltage_core@east.ncc.go.jp

Japan3 sites, 3 recruiting

  • National Cancer Center Hospital East

    Kashiwa, Chiba

    Recruiting

  • Osaka National Hospital

    Osaka

    Recruiting

  • Hokkaido University

    Sapporo, Hokkaido

    Recruiting

Other trials in Japan

About this study

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

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.

Read the 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] PhaseⅡ is composed of 4 cohorts.

Cohort A: First-onset rectal cancer cohort (42 cases) To evaluate the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered following preoperative CRT.

And to search for biomarkers related to therapeutic effects in first-onset cases. Evaluate the safety of surgical treatment.

Cohort B: Rectal cancer with localized recurrence cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT.

Search for biomarkers related to therapeutic effects in localized recurrence cases. Conduct an exploratory evaluation on the safety of surgical treatment.

Cohort C: Rectal cancer with resectable lung/liver metastasis cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT.

Search for biomarkers related to therapeutic effects in resectable lung/liver metastasis cases. Conduct an exploratory evaluation on the safety of surgical treatment.

Cohort D: First-onset rectal cancer using ipilimumab-nivolumab combination cohort (25 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (240 mg/body at two-week intervals) and ipilimumab (1 mg/kg at six-week intervals) after preoperative CRT, and search for biomarkers related to therapeutic effects in first-onset cases. Conduct an exploratory evaluation on the safety of surgical treatment.

Being tested
Nivolumab, Ipilimumab
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo, Chemoradiotherapy with capecitabine, Surgical therapy

    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).

  • IpilimumabDrug

    Also called Yervoy

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

Study groups in NCT02948348
Study groupRoleWhat they receive
Nivolumab & Ipilimumab(Only Cohort D)Experimentalchemoradiotherapy with capecitabine+ Nivolumab + Ipilimumab(Only Cohort D) + surgical therapy
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological complete response

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

    Measured: 1 year

Secondary outcomes (9)

  1. Objective response rate

    Evaluation Criteria In Solid Tumors (RECIST)

    Measured: 1 year

  2. Recurrence pattern (local or distant)

    Measured: 1 year

  3. Disease-free survival (DFS)

    Evaluation Criteria In Solid Tumors (RECIST)

    Measured: 5years

  4. Overall survival (OS)

    Evaluation Criteria In Solid Tumors (RECIST)

    Measured: 5years

  5. Incidence of adverse events (AEs)

    Safety will be evaluated with CTCAE v4.0

    Measured: 1 year

  6. Rate of completing the protocol therapy

    Measured: 1 year

  7. Rate of radical resection

    Measured: 1 year

  8. Safety evaluation

    Safety will be evaluated with CTCAE v4.0

    Measured: 5years

  9. macroscopic evaluation of (rectal cancer) resected specimen

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2016 (estimated)
  2. Study startOct 2016
  3. Primary completionDec 2021 (estimated)
  4. Study completionAug 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02948348
Sponsor's protocol ID
EPOC1504
Status last verified
Sep 2021
First submitted
8 Sep 2016
Last updated
16 Sep 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 38834744

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab and Ipilimumab in people with Cancer of Rectum, run by Takayuki Yoshino at 3 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 16 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Hideaki Bando, Dr (+81-52-762-6111, voltage_core@east.ncc.go.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02948348, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2021.

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