Clinical Trials /

A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC

NCT02860546

Description:

A Phase 2 Study with Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients with Microsatellite Stable Refractory Metastatic Colorectal Cancer

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC
  • Official Title: A Phase 2 Study With Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients With Microsatellite Stable Refractory Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: TAS-102-203
  • NCT ID: NCT02860546

Conditions

  • Refractory Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
TAS-102Lonsurf®TAS-102 and Nivolumab
nivolumabOpdivo®TAS-102 and Nivolumab

Purpose

A Phase 2 Study with Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients with Microsatellite Stable Refractory Metastatic Colorectal Cancer

Detailed Description

      This is a multicenter, single arm, safety lead-in, Phase 2 study, using Simon's 2 stage
      design evaluating the safety and efficacy of TAS-102 plus nivolumab in patients with
      Microsatellite-stable refractory metastatic colorectal cancer

      Stage 1: Patients will be enrolled and after Cycle 1 treatment, they will be evaluated for
      the safety and tolerability of the combination therapy. Assuming a tolerated dose is
      confirmed additional patients evaluable for response will be enrolled and followed for a
      minimum of 6 months and there will be an interim analysis to assess the safety and efficacy
      to determine whether the second stage will open for enrollment.

      Stage 2: Additional patients evaluable for response assessment will be enrolled and followed
      for a minimum of 6 months.
    

Trial Arms

NameTypeDescriptionInterventions
TAS-102 and NivolumabExperimental
  • TAS-102
  • nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Has provided written informed consent.

          2. Patient with confirmed histologically proven metastatic or locally advanced
             colorectal adenocarcinoma who are MSS (ie, not MSI) based on either an analysis of
             tissue from a prior biopsy or based on tissue from a new biopsy.

          3. Patient with the presence of at least 1 lesion with measurable disease as defined by
             10 mm in the longest diameter for a soft tissue lesions or 15 mm in the short axis
             for a lymph node by RECIST and irRC criteria for a response assessment.

          4. Patient has received at least 2 prior lines of standard chemotherapies for mCRC and
             is refractory to or failing those chemotherapies.

          5. Age ≥ 18 years.

          6. Eastern Cooperative Oncology Group performance status of 0 to 1

          7. Life expectancy of ≥ 4 months.

          8. Has adequate organ function

          9. Women of childbearing potential must have a negative pregnancy test (urine or serum)
             within 7 days before starting study drugs. Is able to take medications orally

        Exclusion Criteria:

          1. Has a serious illness or medical condition

          2. Treatment with any of the following within the specified time frame before
             enrollment:

               1. Major surgery within the past 4 weeks (the surgical incision should be fully
                  healed before study drug administration).

               2. Any anticancer therapy within the past 3 weeks before enrollment.

               3. Extended field radiation within the past 4 weeks or limited field radiation
                  within the past 2 weeks before enrollment.

               4. Any investigational drug/device received within the past 4 weeks or 5 times the
                  half-life (whichever is shorter) before enrollment.

          3. Previous treatment with TAS-102.

          4. Prior treatment with anti-PD-1, anti- PD-L1, anti programmed cell death ligand 2,
             anti-CD137, anti-OX-40, anti CD40, anti cytotoxic T lymphocyte associated antigen-4
             antibodies, or any other immune checkpoint inhibitors.

          5. Unresolved toxicity of ≥ Common Terminology Criteria for Adverse Events version
             (CTCAE) version 4.03 grade 2 attributed to any prior therapies (excluding anemia,
             alopecia, skin pigmentation, and platinum induced neurotoxicity).

          6. Prior events of immune-mediated pneumonitis, immune-mediated colitis, immune-mediated
             hepatitis, immune-mediated endocrinopathies, immune mediated nephritis and renal
             dysfunction, immune mediated rash, immune mediated encephalitis, and history of
             infusion reactions to nivolumab.

          7. Known or assumed hypersensitivity to TAS-102 or nivolumab or any of its ingredients,
             including polysorbate 80-containing infusion.

          8. Previous severe hypersensitivity reaction to treatment with another mAb.

          9. Pregnant or lactating female.

         10. Inappropriate for entry into this study in the judgment of the investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune-related overall response rate (irORR)
Time Frame:Up to 2 Years
Safety Issue:
Description:Immune-related overall response rate (irORR) is defined as as the incidence of complete (irCR) and partial (irPR) responses in the efficacy population

Secondary Outcome Measures

Measure:Recommended Phase 2 dose for the combination therapy of TAS 102 and nivolumab
Time Frame:4 Months
Safety Issue:
Description:To confirm the recommended Phase 2 dose
Measure:Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time Frame:Up to 2 Years
Safety Issue:
Description:Safety and Tolerability is defined as AEs graded using NCI criteria for AEs (CTCAE)
Measure:Overall Response Rate (ORR)
Time Frame:Up to 2 Years
Safety Issue:
Description:To estimate the ORR using Response Evaluation Criteria in Solid Tumors (RECIST)
Measure:Progression Free Survival (PFS) based on irRC
Time Frame:Up to 2 Years
Safety Issue:
Description:PFS is defined as the time from the date of randomization until radiological disease based on immune-related response criteria (irRC) or death
Measure:Progression Free Survival (PFS) based on RECIST
Time Frame:Up to 2 Years
Safety Issue:
Description:PFS is defined as the time from the date of randomization until radiological disease based on RECIST or death
Measure:Disease Control Rate (DCR) based on irRC
Time Frame:Up to 2 Years
Safety Issue:
Description:DCR is defined as the proportion of patients with objective evidence of complete response, partial response and stable disease based on irRC
Measure:Disease Control Rate (DCR) based on RECIST
Time Frame:Up to 2 Years
Safety Issue:
Description:DCR is defined as the proportion of patients with objective evidence of complete response, partial response and stable disease based on RECIST
Measure:Overall Survival (OS)
Time Frame:Up to 2 Years
Safety Issue:
Description:To estimate the OS

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Taiho Oncology, Inc.

Trial Keywords

  • Refractory
  • Metastatic
  • Colorectal cancer
  • TAS-102
  • Nivolumab
  • Microsatellite Stable
  • Programmed cell death protein1 (PD 1)

Last Updated

September 9, 2016