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

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ClinicalTrials.gov Identifier: NCT02943733
Recruitment Status : Recruiting
First Posted : October 25, 2016
Last Update Posted : June 18, 2020
Sponsor:
Collaborator:
Taiho Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE October 21, 2016
First Posted Date  ICMJE October 25, 2016
Last Update Posted Date June 18, 2020
Actual Study Start Date  ICMJE August 22, 2017
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2016)
  • Part 1: Maximum Tolerated Dose (MTD) of TAS-102 [ Time Frame: Up to 2 years ]
    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).
  • Part 2: Overall Response Rate [ Time Frame: Up to 5 years ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2016)
  • Part 2: Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
    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.
  • Part 2: Overall Survival [ Time Frame: Up to 5 years ]
    Defined as the time from the start of treatment to the date of expiration. Analyzed using the Kaplan-Meier method.
  • Part 2: Disease Control Rate [ Time Frame: Up to 5 years ]
    Defined as the percentage of patients who achieved complete response, partial response, and stable disease by investigator assessment as per RECIST.
  • Part 2: Duration of Response [ Time Frame: Up to 5 years ]
    Analyzed using the Kaplan-Meier method.
  • Part 2: Safety and Tolerability, Assessed per RECIST Criteria [ Time Frame: Up to 5 years ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
  • Part 2: Biochemical Response defined as normalization or >50% reduction in levels of Chromogranin A [ Time Frame: Up to 5 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs
Official Title  ICMJE Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic Neuroendocrine Tumors
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroendocrine Tumors
  • Neoplasms
  • Cancer
  • Tumors
Intervention  ICMJE
  • Drug: TAS-102
    Anti-metabolite agent, taken orally.
  • Drug: Temozolomide
    Oral chemotherapy drug.
    Other Name: TMZ
  • 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.
Study Arms  ICMJE 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 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.

Interventions:
  • Drug: TAS-102
  • Drug: Temozolomide
  • Drug: Filgrastim
  • Drug: Pegfilgrastim
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 13, 2017)
33
Original Estimated Enrollment  ICMJE
 (submitted: October 21, 2016)
39
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cancer Connect 800-622-8922 clinicaltrials@cancer.wisc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02943733
Other Study ID Numbers  ICMJE UW16034
NCI-2016-01567 ( Registry Identifier: NCI CTRP ID )
2016-0930 ( Other Identifier: Institutional Review Board )
A534260 ( Other Identifier: UW Madison )
SMPH\MEDICINE\HEM-ONC ( Other Identifier: UW Madison )
Protocol Version 12/30/2019 ( Other Identifier: UW Madison )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE Taiho Pharmaceutical Co., Ltd.
Investigators  ICMJE
Principal Investigator: Nataliya Uboha, MD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP