TAS-102 and Temozolomide in Treating Patients with Metastatic Neuroendocrine Tumors

Status: Active

Description

This phase IB trial studies the side effects and best dose of temozolomide when given together with trifluridine and tipiracil hydrochloride (TAS-102) and to see how well they work in treating patients with neuroendocrine tumors that have spread to other places in the body. Drugs used in chemotherapy, such as TAS-102 and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Eligibility Criteria

Inclusion Criteria

  • Patients with histologically or cytologically confirmed metastatic or locally advanced NETs of any origin and grade (Part 1)
  • Patients with histologically confirmed unresectable or metastatic pancreatic (p)NETs of grade 1 or 2; grade 3 tumors or tumors with small cell histology will be excluded (Part 2)
  • Presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (not required for Part 1); presence of evaluable OR measurable disease for Part 1
  • Concurrent somatostatin analogues are allowed provided that the dose has been stable (+/- 10 mg) for at least 8 weeks
  • Prior chemoembolization or radiation therapy (including Y90) must be performed at least 2 weeks before study enrollment
  • Eastern Cooperative Oncology Group (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
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) (=< 5 x ULN in case of liver metastases)
  • Total serum bilirubin of =< 1.5 x institutional ULN
  • 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

  • Previous treatment with TAS-102 or TMZ
  • History of partial or total gastrectomy
  • Symptomatic central nervous system (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 at the time of study treatment initiation
  • 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 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 with most recent hemoglobin A1C > 9 performed in last 6 months; this requirement is for subjects with known history of diabetes mellitus only
  • Complete or partial intestinal obstruction at the time of study enrollment
  • Known history of pulmonary fibrosis
  • Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV
  • Grade 2 or higher ongoing gastrointestinal hemorrhage; patients with grade 1 gastrointestinal bleeding are eligible for participation

Locations & Contacts

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Nataliya V. Uboha
Phone: 608-265-1700
Email: nvuboha@medicine.wisc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To investigate the safety and determine the maximum tolerated dose (MTD) of temozolomide (TMZ) administered in combination with TAS-102 in patients with advanced neuroendocrine tumors (NETs). (Part I)

II. Further evaluate the safety and tolerability of the studied drug combination. (Part 2)

OUTLINE: This is a dose-escalation study of temozolomide.

Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and 8-12 and temozolomide PO daily on days 8-12. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 16 weeks for up to 3 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
Nataliya V. Uboha

Trial IDs

Primary ID UW16034
Secondary IDs NCI-2016-01567
Clinicaltrials.gov ID NCT02943733