Clinical trial NCT02860546: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Metastatic Colorectal Cancer
Keywords: Refractory
Metastatic
Colorectal cancer
TAS-102
Nivolumab
Microsatellite Stable
Programmed cell death protein1 (PD 1)
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2016-08-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase 2 Study with Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Participants 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 participants with Microsatellite-stable refractory metastatic colorectal cancer

Stage 1: Participants 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 participants 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 participant evaluable for response assessment will be enrolled and followed for a minimum of 6 months.

Eligibility criteria: Inclusion Criteria:

1. Has provided written informed consent.
2. Participants with confirmed histologically proven metastatic or locally advanced colorectal adenocarcinoma who are microsatellite stable (MSS) (ie, not microsatellite instable \[MSI\]) based on either an analysis of tissue from a prior biopsy or based on tissue from a new biopsy.
3. Participants with the presence of at least 1 lesion with measurable disease as defined by 10 millimeters (mm) in the longest diameter for a soft tissue lesions or 15 mm in the short axis for a lymph node by response evaluation criteria in solid tumors (RECIST) and immune related response-criteria (irRC) for a response assessment.
4. Participants has received at least 2 prior lines of standard chemotherapies for metastatic colorectal cancer (mCRC) and is refractory to or failing those chemotherapies.
5. Age greater than or equal to (\>=) 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.
10. 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-programmed cell death-1 (anti-PD-1), anti-programmed cell death ligand (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.

Primary outcomes:
measure: Immune-Related Overall Response Rate (irORR)
timeFrame: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Secondary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (each cycle is of 4 weeks)
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Cycle 1 (each cycle is of 4 weeks)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
measure: Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
timeFrame: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
measure: Overall Response Rate (ORR)
timeFrame: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
measure: Progression-Free Survival (PFS) Based on Immune Related Response-Criteria (irRC)
timeFrame: From the first dose of study treatment to disease progression or death (up to 53 weeks)
measure: Progression-Free Survival (PFS) Based on RECIST Criteria
timeFrame: From the first dose of study treatment to disease progression or death (up to 53 weeks)
measure: Disease Control Rate (DCR) Based on irRC Criteria
timeFrame: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
measure: Disease Control Rate (DCR) Based on RECIST Criteria
timeFrame: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
measure: Overall Survival (OS)
timeFrame: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
References:
citation: Patel MR, Falchook GS, Hamada K, Makris L, Bendell JC. A phase 2 trial of trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable metastatic colorectal cancer. Cancer Med. 2021 Feb;10(4):1183-1190. doi: 10.1002/cam4.3630. Epub 2021 Feb 5.