Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs

NCT ID: NCT02943733

Last Updated: 2022-09-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-22
• Study Completion Date: 2022-01-31

Brief Summary

The goal of this study is to establish maximum tolerated doses/recommended phase 2 dose (RP2D) of temozolomide (TMZ) and TAS-102 when these agents are used in combination and to evaluate the safety profile of this drug combination.

Detailed Description

The study is a two part phase 1B clinical trial consisting of three study periods: a screening period of 14 days or less, a treatment period, and a safety follow-up period 30 days after treatment discontinuation.

Part 1 is a dose finding phase with the objective to assess the safety and tolerability of the proposed drug combination and to identify the maximum tolerated dose (MTD) and a recommended phase 2 dose.

Part 2 is an open-label expansion study, which will enroll patients with metastatic pNETs who have not been previously treated with chemotherapy. Part 2 will obtain further safety data of the proposed drug combination.

Conditions

Neuroendocrine Tumors; Neoplasms; Cancer; Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TAS-102 and TMZ

Part 1: dose-escalation phase to determine MTD of TAS-102 in combination with Temozolomide (TMZ). Treatment cycles are 28 days, with TAS-102 administered orally twice daily days 1-5 and 8-12, and TMZ administered orally days 8-12. No treatment medications administered days 13-28 of each cycle. Growth factor support is required during Part 1 and should be dosed per institutional standards.

Part 2: expansion phase to evaluate preliminary efficacy of MTD. Subjects treated with the recommended phase 2 drug doses determined in part 1. Treatment will continue for up to 13 cycles (approx. 12 months). Growth factor support is allowed during Part 2 and should be dosed per institutional standards.

Group Type: EXPERIMENTAL

TAS-102

Intervention Type: DRUG

Anti-metabolite agent, taken orally.

Temozolomide

Intervention Type: DRUG

Oral chemotherapy drug.

Filgrastim

Intervention Type: DRUG

Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Pegfilgrastim

Intervention Type: DRUG

Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Interventions

TAS-102

Anti-metabolite agent, taken orally.

Intervention Type: DRUG

Temozolomide

Oral chemotherapy drug.

Intervention Type: DRUG

Filgrastim

Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Intervention Type: DRUG

Pegfilgrastim

Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Intervention Type: DRUG

Other Intervention Names

TMZ

Eligibility Criteria

Inclusion Criteria

• Part 1: Patients with histologically or cytologically confirmed metastatic or locally advanced NETs of any origin and grade
• Part 1: Presence of evaluable OR measurable disease
• Part 2: Patients with histologically confirmed unresectable or metastatic pNETs of grade 1 or 2.
• Part 2: Presence of measurable disease by RECIST 1.1 criteria
• Concurrent somatostatin analogues are allowed provided that the dose has been stable (+/- 10mg) for at least 8 weeks
• Prior chemoembolization or radiation therapy (including Y90) must be performed at least 2 weeks before study enrollment
• ECOG performance status 0-2
• Life expectancy more than 3 months
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin ≥ 9 g/dL
• Platelets ≥ 100 x 10^9/L
• AST/ALT ≤ 3 x ULN (≤5 x ULN in case of liver metastases)
• Total serum bilirubin of ≤ x institutional ULN (except for Grade 1 hyperbilirubinemia solely due to a medical diagnosis of Gilbert's syndrome)
• Serum creatinine ≤ 1.5 x institutional ULN (Cockcroft and Gault formula)
• Ability to take oral medication (i.e. no feeding tube)
• Female patients of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to the start of the study drug treatment and must agree to use adequate birth control if conception is possible during the study and up to 6 months after discontinuation of study drug treatment
• Male patients must agree to use adequate birth control during the study and up to 6 months after discontinuation of study drug treatment
• Women who are nursing must discontinue breast feeding prior to the enrollment in the trial
• Patient must be able and willing to comply with study procedures as per protocol
• Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures

Exclusion Criteria

• Part 2: Grade 3 tumors or tumors with small cell histology will be excluded
• Previous treatment with TAS-102 or TMZ
• History of partial or total gastrectomy
• Symptomatic CNS metastases requiring treatment
• Prior radiation therapy irradiating more than 10% of total bone marrow
• Other active malignancy requiring treatment within the last 2 years (except for non-melanoma skin cancer, a non-invasive/in situ cancer, or indolent nonmetastatic Gleason 6 prostate cancer)
• Pregnancy or breast feeding
• Active infection requiring treatment
• Known chronic infection with human immunodeficiency virus, hepatitis B, or hepatitis C
• Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration)
• Any anticancer therapy treatments, including other investigational agents within prior 2 weeks
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102 or TMZ
• Extended field radiation within prior 4 weeks or limited field radiation within prior 2 weeks
• Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule
• Ascites, pleural effusion or pericardial fluid requiring drainage in the last 4 weeks
• Uncontrolled diabetes mellitus
• Intestinal obstruction
• Pulmonary fibrosis
• Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure NYHA class III or IV
• Gastrointestinal hemorrhage

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taiho Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nataliya Uboha, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Countries

United States

Related Links

https://cancer.wisc.edu/

UW Carbone Cancer Center Home Page

Other Identifiers

NCI-2016-01567

Identifier Type: REGISTRY

Identifier Source: secondary_id

2016-0930

Identifier Type: OTHER

Identifier Source: secondary_id

A534260

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH\MEDICINE\HEM-ONC

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Ver 5.0 12/30/2019

Identifier Type: OTHER

Identifier Source: secondary_id

UW16034

Identifier Type: -

Identifier Source: org_study_id