Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

NCT02831179 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: VICC GI 14134NCI-2016-01044
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I trial studies the side effects and best dose of veliparib when given together with capecitabine and temozolomide in treating patients with neuroendocrine tumor that has spread to other places in the body and usually cannot be cured or controlled with treatment, has returned after a period of improvement, and cannot be removed by surgery. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as capecitabine 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.

Conditions

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose determined by dose limiting toxicities defined as any toxicity in the first course evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 28 days

Secondary Outcomes (5)

• Response rate measured as complete response, partial response or stable disease according to RECIST 1.1 criteria

  56 days (2 courses)

• Response duration

  Up to 4 weeks

• Progression Free Survival

  From start of treatment to time of progression or death, assessed up to 4 weeks

• Overall Survival

  Up to 4 weeks

• Poly-adenosine diphosphate (ADP)-ribosylated (PAR) level

  Baseline to day 15 of course 1

Study Arms (1)

Treatment (capecitabine, temozolomide, veliparib)

EXPERIMENTAL

Capecitabine PO BID on days 1-14, temozolomide PO BID on days 10-14 and veliparib PO BID on days 10-14.

Drug: Capecitabine; Drug: Temozolomide; Drug: Veliparib; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

Interventions

Capecitabine DRUG

Given PO

Treatment (capecitabine, temozolomide, veliparib)

Temozolomide DRUG

Given PI

Treatment (capecitabine, temozolomide, veliparib)

Veliparib DRUG

given PO

Treatment (capecitabine, temozolomide, veliparib)

Pharmacological Study OTHER

Correlative studies

Treatment (capecitabine, temozolomide, veliparib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (capecitabine, temozolomide, veliparib)

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed metastatic unresectable well differentiated (low grade and intermediate grade) neuroendocrine tumors (Ki-67 \< 20% and mitotic rate \< 2 per 10 high power field) that demonstrate progressive disease (by serial computed tomography \[CT\] or magnetic resonance imaging \[MRI\] scans) in past 12 months including
• Carcinoid tumors originating anywhere in the body including the gastrointestinal (GI) tract or bronchial tree or thymus
• Pancreatic neuroendocrine tumors (including functional and non-functional islet cell, insulinomas and glucagonomas)
• Pheochromocytomas
• Gastrinomas (Zollinger-Ellison syndrome)
• Multiple endocrine neoplasia (MEN type I/II),
• Adrenal carcinomas with NET markers by immunohistochemistry (IHC) or serum
• Somatostatinoma
• VIPoma (vasoactive intestinal peptide)
• Merkel cell tumors
• Medullary thyroid carcinoma
• Neuroendocrine tumors of unknown primary site
• Patients must have progressed on octreotide therapy and/or radioactive isotopes linked to octreotide or its congeners if they had a positive octreotide scan; patients who have negative or mildly positive octreotide scans are exempt from this requirement
• Somatostatin analogs can be continued at their tolerated dose in patients with functional symptoms related to underlying disease such as in functional islet cell, insulinomas, glucagonomas etc
• Patients may have received prior chemotherapy for advanced disease including either capecitabine or temozolomide single agent as long as it did not include combination of capecitabine and temozolomide

You may not qualify if:

• Prior chemotherapy with combination of capecitabine (or 5-flourouracil \[5-FU\]) "and" temozolomide (or dacarbazine \[DTIC\]) will be excluded; patients can have had prior therapies up to 3 prior chemotherapy regimens such as streptozocin, anthracyclines, irinotecan, etoposide, or a platinum agent including single agent capecitabine (or 5FU) or temozolomide (or DTIC).
• History of severe hypersensitivity reaction to capecitabine, 5-FU, temozolomide or DTIC will be excluded (i.e. anaphylaxis or anaphylactoid reactions)
• Patients who have active or uncontrolled infection or serious medical or psychiatric illness preventing informed consent or on intensive treatment
• Patients with brain metastases are excluded
• Patients with uncontrolled seizures or any neurological conditions resulting in increased risk for seizures are not eligible for study entry
• Patients with documented central nervous system (CNS) ischemia and/or infarction, whether symptomatic or discovered incidentally without clinical symptoms, will be excluded from study participation
• Patients with a history of the arterial or venous thromboembolism within =\< 12 months of study entry are not eligible
• Human immunodeficiency virus (HIV)-positive patients on antiretroviral therapy are excluded from the study
• Patients with another active malignancy within the past five years except for carcinoma in situ of cervix or in situ carcinoma of the bladder or non-melanomatous carcinoma of the skin
• Clinically significant and uncontrolled major medical conditions including but not limited to: active uncontrolled infection, psychiatric illness/ social situation that would limit compliance with study requirements; any medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities
• Patients who are receiving any other investigational agents
• Major surgical procedure within 4 weeks of treatment
• Patients may not have any clinically significant cardiovascular disease including the following:
• Myocardial infarction or ventricular tachyarrhythmia within 6 months
• Prolonged QTc \> 480 msec at baseline

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Pheochromocytoma; Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Neuroendocrine Tumors; Non functioning pancreatic endocrine tumor; Glucagonoma; Insulinoma; Adrenal Cortex Neoplasms; Somatostatinoma; Carcinoma, Medullary; Vipoma; Zollinger-Ellison Syndrome

Interventions

Capecitabine; Temozolomide; veliparib

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Paraganglioma; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Carcinoma, Islet Cell; Pancreatic Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases; Adenoma, Islet Cell; Adenoma; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Neoplasms, Ductal, Lobular, and Medullary; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles

Study Officials

• Jordan Berlin, M.D.

  Vanderbilt-Ingram Cancer Center

  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: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 10, 2016
• First Posted: July 13, 2016
• Study Start: December 1, 2017
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2020
• Last Updated: September 28, 2017

Record last verified: 2017-09