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

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ClinicalTrials.gov Identifier: NCT02860546
Recruitment Status : Completed
First Posted : August 9, 2016
Last Update Posted : September 19, 2018
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.

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

Condition or disease Intervention/treatment Phase
Refractory Metastatic Colorectal Cancer Drug: TAS-102 Drug: nivolumab Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study With Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients With Microsatellite Stable Refractory Metastatic Colorectal Cancer
Study Start Date : August 2016
Actual Primary Completion Date : November 3, 2017
Actual Study Completion Date : November 3, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: TAS-102 and Nivolumab Drug: TAS-102
One Arm Only (of TAS 102 plus nivolumab)
Other Name: Lonsurf®

Drug: nivolumab
One Arm Only (of TAS 102 plus nivolumab)
Other Name: Opdivo®




Primary Outcome Measures :
  1. Immune-related overall response rate (irORR) [ Time Frame: Up to 2 Years ]
    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 :
  1. Recommended Phase 2 dose for the combination therapy of TAS 102 and nivolumab [ Time Frame: 4 Months ]
    To confirm the recommended Phase 2 dose

  2. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 2 Years ]
    Safety and Tolerability is defined as AEs graded using NCI criteria for AEs (CTCAE)

  3. Overall Response Rate (ORR) [ Time Frame: Up to 2 Years ]
    To estimate the ORR using Response Evaluation Criteria in Solid Tumors (RECIST)

  4. Progression Free Survival (PFS) based on irRC [ Time Frame: Up to 2 Years ]
    PFS is defined as the time from the date of randomization until radiological disease based on immune-related response criteria (irRC) or death

  5. Progression Free Survival (PFS) based on RECIST [ Time Frame: Up to 2 Years ]
    PFS is defined as the time from the date of randomization until radiological disease based on RECIST or death

  6. Disease Control Rate (DCR) based on irRC [ Time Frame: Up to 2 Years ]
    DCR is defined as the proportion of patients with objective evidence of complete response, partial response and stable disease based on irRC

  7. Disease Control Rate (DCR) based on RECIST [ Time Frame: Up to 2 Years ]
    DCR is defined as the proportion of patients with objective evidence of complete response, partial response and stable disease based on RECIST

  8. Overall Survival (OS) [ Time Frame: Up to 2 Years ]
    To estimate the OS


Other Outcome Measures:
  1. MSI status by Polymerase Chain Reaction (PCR) with clinical and toxicity [ Time Frame: Up to 2 Years ]
    To explore the association of MSI status by polymerase chain reaction (PCR) with clinical response and toxicity

  2. PD L1 positivity by Immunohistochemistry (IHC) with clinical and toxicity [ Time Frame: Up to 2 Years ]
    To explore the association of programmed cell death ligand 1 (PD L1) positivity by Immunohistochemistry (IHC) with clinical response and toxicity

  3. Tumor infiltrating lymphocyte characteristics by Flow Cytometry with clinical and toxicity [ Time Frame: Up to 2 Years ]
    To explore the association of tumor infiltrating lymphocyte characteristics by Flow cytometry with clinical response and toxicity



Information from the National Library of Medicine

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

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 ClinicalTrials.gov identifier (NCT number): NCT02860546


Locations
United States, Colorado
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States, 80218
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Taiho Oncology, Inc.

Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02860546     History of Changes
Other Study ID Numbers: TAS-102-203
First Posted: August 9, 2016    Key Record Dates
Last Update Posted: September 19, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Study results using compiled efficacy and safety data will be published at congress or to a journal, without any identification of the patients.

Keywords provided by Taiho Oncology, Inc.:
Refractory
Metastatic
Colorectal cancer
TAS-102
Nivolumab
Microsatellite Stable
Programmed cell death protein1 (PD 1)

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Nivolumab
Antibodies, Monoclonal
Trifluridine
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents