Trials / Active Not Recruiting

Active Not RecruitingNCT04394858

Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer

A Prospective, Multi-Institutional Phase II Trial Evaluating Temozolomide vs. Temozolomide and Olaparib for Advanced Pheochromocytoma and Paraganglioma

Status: Active Not Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 46 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 12 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies how well the addition of olaparib to the usual treatment, temozolomide, works in treating patients with neuroendocrine cancer (pheochromocytoma or paraganglioma) that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Poly (adenosine diphosphate \[ADP\]-ribose) polymerases (PARPs) are proteins that help repair deoxyribonucleic acid (DNA) mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Chemotherapy drugs, such as 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. Giving olaparib with temozolomide may shrink or stabilize the cancer in patients with pheochromocytoma or paraganglioma better than temozolomide alone.

Detailed description

PRIMARY OBJECTIVE: I. To compare the progression-free survival (PFS) of patients with advanced pheochromocytoma and paraganglioma (APP) receiving temozolomide (dose dense) and olaparib to that of patients receiving temozolomide (pulse dose) alone. SECONDARY OBJECTIVES: I. To compare the overall survival (OS) of patients with APP receiving temozolomide (dose dense) and olaparib versus (vs.) temozolomide (pulse dose) alone. II. To compare the objective response rate (ORR) associated with temozolomide (dose dense) and olaparib vs. temozolomide (pulse dose) alone in patients with APP. III. To evaluate and compare the toxicity profile of temozolomide-based combinations (temozolomide \[dose dense\] and olaparib vs. temozolomide \[pulse dose\]) in patients with APP using Common Terminology Criteria for Adverse Events (CTCAE) and Patient-Reported Outcomes (PRO)-CTCAE. OTHER OBJECTIVE: I. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue. EXPLORATORY OBJECTIVES: I. To assess biochemical response: serum catecholamines and metanephrines; urine catecholamines and metanephrines. II. To assess biomolecular markers associated with clinical outcome: germline succinyl dehydrogenase (SDH) mutations and tumor status of the repair enzyme methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive temozolomide orally (PO) once daily (QD) and olaparib PO twice daily (BID) on days 1-7. Treatment with temozolomide repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Cycles of olaparib repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) with contrast or magnetic resonance imaging (MRI) throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression. ARM II: Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with contrast or MRI throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression. Patients discontinuing treatment due to reasons other than disease progression are followed every 12 weeks until disease progression, then every 6 months until 5 years after registration. Patients discontinuing treatment due to disease progression are followed every 6 months for 5 years after registration.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography with Contrast	Undergo CT with contrast
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Olaparib	Given PO
OTHER	Quality-of-Life Assessment	Ancillary studies
DRUG	Temozolomide	Given PO

Timeline

Start date: 2021-03-17
Primary completion: 2028-03-01
Completion: 2028-03-01
First posted: 2020-05-20
Last updated: 2026-04-13

Locations

163 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04394858. Inclusion in this directory is not an endorsement.