Safety Of TAS-102 In Combination With Temozolomide For Metastatic Pancreatic NETs

Study Overview

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

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.

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.

Neuroendocrine Tumors
Neoplasms
Cancer
Tumors

DRUG: TAS-102
DRUG: Temozolomide
DRUG: Filgrastim
DRUG: Pegfilgrastim

UW16034
NCI-2016-01567 (REGISTRY Identifier) (REGISTRY: NCI CTRP ID)
2016-0930 (OTHER Identifier) (OTHER: Institutional Review Board)
A534260 (OTHER Identifier) (OTHER: UW Madison)
SMPHMEDICINEHEM-ONC (OTHER Identifier) (OTHER: UW Madison)
Protocol Ver 5.0 12/30/2019 (OTHER Identifier) (OTHER: UW Madison)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-10-21	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-09-21
First Submitted that Met QC Criteria 2016-10-21	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-09-23
First Posted (ACTUAL) 2016-10-25	Results First Posted N/A	Last Verified 2022-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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	DRUG: TAS-102 Anti-metabolite agent, taken orally. DRUG: Temozolomide Oral chemotherapy drug. DRUG: Filgrastim Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy. DRUG: Pegfilgrastim Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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

DRUG: TAS-102

Anti-metabolite agent, taken orally.

DRUG: Temozolomide

Oral chemotherapy drug.

DRUG: Filgrastim

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

DRUG: Pegfilgrastim

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

Primary Outcome Measures	Measure Description	Time Frame
Part 1: Maximum Tolerated Dose (MTD) of TAS-102	Investigate the safety and determine the MTD of TAS-102 administered in combination with TMZ in patients with advanced NETs. Treatments will continue to disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST).	Up to 2 years
Part 2: Overall Response Rate	Response rate defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR), assessed as per RECIST criteria. Assessments performed using RECIST criteria.	Up to 5 years

Secondary Outcome Measures	Measure Description	Time Frame
Part 2: Progression Free Survival (PFS)	Defined as the time from the start of treatment to the date of first documented progression or any cause of death during the study, assessed according to RECIST. Analyzed using the Kaplan-Meier method.	Up to 5 years
Part 2: Overall Survival	Defined as the time from the start of treatment to the date of expiration. Analyzed using the Kaplan-Meier method.	Up to 5 years
Part 2: Disease Control Rate	Defined as the percentage of patients who achieved complete response, partial response, and stable disease by investigator assessment as per RECIST.	Up to 5 years
Part 2: Duration of Response	Analyzed using the Kaplan-Meier method.	Up to 5 years
Part 2: Safety and Tolerability, Assessed per RECIST Criteria	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Up to 5 years
Part 2: Biochemical Response defined as normalization or >50% reduction in levels of Chromogranin A	A major biochemical response will be defined as normalization or >50% reduction in levels of Chromogranin A. Chromogranin A is elevated in up to 60% of functioning and nonfunctioning pancreatic endocrine tumors.	Up to 5 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Taiho Pharmaceutical Co., Ltd.

Investigators

PRINCIPAL_INVESTIGATOR: Nataliya Uboha, MD, University of Wisconsin, Madison

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record