Functional Pancreatic Neuroendocrine TumorPhase 1NCT02831179

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

A Phase 1 study testing Capecitabine, Temozolomide and Veliparib in people with Functional Pancreatic Neuroendocrine Tumor and Malignant Somatostatinoma, run by Vanderbilt-Ingram Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Functional Pancreatic Neuroendocrine Tumor, Malignant Somatostatinoma, Merkel Cell Carcinoma
What is being tested?: Capecitabine, Temozolomide and Veliparib
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: Dec 2017to Feb 2020
Phase: Phase 1

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

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),

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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
Patients must have completed prior (non-excluded) anti-cancer therapy (including surgery or chemotherapy or hepatic embolization/chemoembolization or radioactive isotopes i.e. yttrium 90) at least 4 weeks prior to day 1
Patients with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intracranial disease and have not had treatment with steroids within 1 week of study enrollment
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Anticipated life expectancy of greater than 3 months
Patients must have measurable disease either primary and/or metastatic masses reproducibly measurable in one or two diameters by Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 parameters by CT scan or MRI scan; positron emission tomography (PET) or octreotide scans are useful adjuncts but will not be used to measure response
Granulocytes > 1,500/ml
Platelets > 100,000/ml
Hemoglobin >= 10 g/dl
Creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance >= 50 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal
Bilirubin < 1.5 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN (< 5 x ULN if liver metastases are present)
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of veliparib, capecitabine and temozolomide administration
Ability to understand and the willingness to sign a written informed consent document
Patients must be able to swallow pills

Who cannot join

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

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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
Symptomatic congestive heart failure (CHF) of New York Heart Association (NYHA) functional class >= 3
Major conduction abnormality (unless a cardiac pacemaker is present)
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with capecitabine or temozolomide or veliparib

About this study

Official title: A Phase 1 Study of Veliparib (ABT-888) in Combination With Capecitabine and Temozolomide in Advanced Well-Differentiated Neuroendocrine Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

To determine the maximum tolerated dose (MTD) of veliparib (ABT-888) in combination with capecitabine and temozolomide in patients with advanced well-differentiated neuroendocrine tumors.

SECONDARY OBJECTIVES:

To determine the safety profile of the combination of capecitabine, temozolomide and veliparib in patients with advanced well-differentiated neuroendocrine tumors (NET).
To evaluate the antitumor activity of the combination of capecitabine, temozolomide and veliparib in advanced well-differentiated NET patients
To determine progression-free survival (PFS) of the combination of capecitabine, temozolomide, and veliparib in advanced well-differentiated NET patients IV. To evaluate the association between pharmacodynamic biomarkers and response in patients with advanced well-differentiated NET patients.

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

Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14, temozolomide PO BID on days 10-14 and veliparib PO BID on days 10-14. Courses repeat every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Conditions: Functional Pancreatic Neuroendocrine Tumor, Malignant Somatostatinoma, Merkel Cell Carcinoma, Metastatic Adrenal Gland Pheochromocytoma, Metastatic Carcinoid Tumor, Multiple Endocrine Neoplasia Type 1
Being tested: Capecitabine, Temozolomide, Veliparib, Pharmacological Study, Laboratory Biomarker Analysis
Medical subject headings: 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

What participants receive

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

CapecitabineDrug
Given PO
TemozolomideDrug
Given PI
VeliparibDrug
given PO
Pharmacological StudyOther
Correlative studies
Laboratory Biomarker AnalysisOther
Correlative studies

Study groups in NCT02831179
Study group	Role	What they receive
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. Receives: Drug: Capecitabine; Drug: Temozolomide; Drug: Veliparib; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

What is being measured

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

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
Measured: Up to 28 days

Secondary outcomes (5)

Response rate measured as complete response, partial response or stable disease according to RECIST 1.1 criteria
Measured: 56 days (2 courses)
Response duration
Measured: Up to 4 weeks
Progression Free Survival
Measured: From start of treatment to time of progression or death, assessed up to 4 weeks
Overall Survival
Measured: Up to 4 weeks
Poly-adenosine diphosphate (ADP)-ribosylated (PAR) level
Measured: Baseline to day 15 of course 1

Timeline

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

Dec 2017Feb 2020

First posted13 Jul 2016 (estimated)
Study startDec 2017 (estimated)
Primary completionFeb 2019 (estimated)
Study completionFeb 2020 (estimated)

Why it stopped: Loss of funding support

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Functional Pancreatic Neuroendocrine TumorStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02831179
Sponsor's protocol ID: VICC GI 14134
Other IDs: NCI-2016-01044
Status last verified: Sep 2017
First submitted: 10 Jul 2016
Last updated: 28 Sep 2017
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided