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

NCT02943733 | Terminated Phase 1 DMC FDA Drug

• 6 other identifiers: UW16034NCI-2016-015672016-0930A534260SMPH\MEDICINE\HEM-ONCProtocol Ver 5.0 12/30/2019
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuroendocrine Tumors; Neoplasms; Cancer; Tumors

Keywords

Pancreatic neuroendocrine tumors (pNETs); Pancreatic neuroendocrine tumors; pNETs; NETs

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Part 2: Progression Free Survival (PFS)

  Up to 5 years

• Part 2: Overall Survival

  Up to 5 years

• Part 2: Disease Control Rate

  Up to 5 years

• Part 2: Duration of Response

  Up to 5 years

• Part 2: Safety and Tolerability, Assessed per RECIST Criteria

  Up to 5 years

Study Arms (1)

TAS-102 and TMZ

EXPERIMENTAL

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.

Drug: TAS-102; Drug: Temozolomide; Drug: Filgrastim; Drug: Pegfilgrastim

Interventions

TAS-102 DRUG

Anti-metabolite agent, taken orally.

TAS-102 and TMZ

Temozolomide DRUG

Oral chemotherapy drug.

Also known as: TMZ

TAS-102 and TMZ

Filgrastim DRUG

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

TAS-102 and TMZ

Pegfilgrastim DRUG

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

TAS-102 and TMZ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Taiho Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• UW Carbone Cancer Center Home Page

MeSH Terms

Conditions

Neuroendocrine Tumors; Neoplasms; Neuroectodermal Tumors, Primitive

Interventions

trifluridine tipiracil drug combination; Temozolomide; Filgrastim; pegfilgrastim

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Nataliya Uboha, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2016
• First Posted: October 25, 2016
• Study Start: August 22, 2017
• Primary Completion: November 7, 2020
• Study Completion: January 31, 2022
• Last Updated: September 23, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)