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Neuroendocrine TumorsPhase 1NCT02943733

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

A Phase 1 study testing TAS-102, Temozolomide and Filgrastim in people with Neuroendocrine Tumors and Neoplasms, run by University of Wisconsin, Madison at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Tumors, Neoplasms, Cancer
What is being tested?
TAS-102, Temozolomide and Filgrastim
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
22 Aug 2017to 31 Jan 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

Other trials in United States

About this study

Official title: Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic Neuroendocrine Tumors

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.

Read the 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.

Being tested
TAS-102, Temozolomide, Filgrastim, Pegfilgrastim
Keywords
Pancreatic neuroendocrine tumors (pNETs), Pancreatic neuroendocrine tumors, pNETs, NETs
Medical subject headings
Neuroendocrine Tumors, Neoplasms, Neuroectodermal Tumors, Primitive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAS-102Drug

    Anti-metabolite agent, taken orally.

  • TemozolomideDrug

    Also called TMZ

    Oral chemotherapy drug.

  • FilgrastimDrug

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

  • PegfilgrastimDrug

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

Study groups in NCT02943733
Study groupRoleWhat they receive
TAS-102 and TMZExperimentalPart 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.
Receives: Drug: TAS-102; Drug: Temozolomide; Drug: Filgrastim; Drug: Pegfilgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Up to 2 years

  2. 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.

    Measured: Up to 5 years

Secondary outcomes (6)

  1. 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.

    Measured: Up to 5 years

  2. Part 2: Overall Survival

    Defined as the time from the start of treatment to the date of expiration. Analyzed using the Kaplan-Meier method.

    Measured: Up to 5 years

  3. 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.

    Measured: Up to 5 years

  4. Part 2: Duration of Response

    Analyzed using the Kaplan-Meier method.

    Measured: Up to 5 years

  5. Part 2: Safety and Tolerability, Assessed per RECIST Criteria

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: Up to 5 years

  6. 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.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2016 (estimated)
  2. Study start22 Aug 2017
  3. Primary completion7 Nov 2020
  4. Study completion31 Jan 2022

Why it stopped: closed per sponsor request, for slow enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02943733
Sponsor's protocol ID
UW16034
Other IDs
NCI-2016-01567, 2016-0930, A534260, SMPH\MEDICINE\HEM-ONC, Protocol Ver 5.0 12/30/2019
Status last verified
Sep 2022
First submitted
21 Oct 2016
Last updated
23 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAS-102, Temozolomide and Filgrastim in people with Neuroendocrine Tumors and Neoplasms, run by University of Wisconsin, Madison at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: closed per sponsor request, for slow enrollment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Maximum Tolerated Dose (MTD) of TAS-102 (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02943733.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2022.

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Clinical Trial NCT02943733 | AzTrials