Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer
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|ClinicalTrials.gov Identifier: NCT04394858|
Recruitment Status : Recruiting
First Posted : May 20, 2020
Last Update Posted : January 20, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Adrenal Gland Pheochromocytoma Advanced Paraganglioma Metastatic Adrenal Gland Pheochromocytoma Metastatic Paraganglioma Unresectable Adrenal Gland Pheochromocytoma Unresectable Paraganglioma||Drug: Olaparib Other: Quality-of-Life Assessment Drug: Temozolomide||Phase 2|
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.
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.
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.
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.
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 discontinuing treatment due to reasons other than disease progression are followed every 8 weeks until disease progression, then every 6 months until 5 years after start of treatment. Patients discontinuing treatment due to disease progression are followed every 6 months for 5 years after start of treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||76 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Prospective, Multi-Institutional Phase II Trial Evaluating Temozolomide vs. Temozolomide and Olaparib for Advanced Pheochromocytoma and Paraganglioma|
|Actual Study Start Date :||November 2, 2020|
|Estimated Primary Completion Date :||February 28, 2023|
|Estimated Study Completion Date :||February 28, 2023|
Experimental: Arm I (temozolomide, olaparib)
Patients receive temozolomide PO QD and olaparib PO 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.
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Active Comparator: Arm II (temozolomide)
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.
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Progression-free survival (PFS) [ Time Frame: From randomization to the first documentation of disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) or death, assessed up to 5 years ]Will be compared between treatment arms using the un-stratified log-rank test at one-sided level of 0.11 and the p-value will be used for decision making. The hazard ratio will be estimated using a Cox proportional hazards model and the 95% confidence interval for the hazard ratio will be provided. Results from a stratified analysis will also be provided. Kaplan-Meier methodology will be used to estimate the median PFS for each treatment arm, and Kaplan-Meier curves will be produced. Brookmeyer-Crowley methodology will be used to construct the 95% confidence interval for the median PFS for each treatment arm.
- Overall survival (OS) [ Time Frame: From randomization to death due to any cause, assessed up to 5 years ]Patients who are alive will be censored at last follow-up. The distribution of survival time will be estimated using the method of Kaplan-Meier. OS will be compared between treatment arms using the log-rank test. OS medians, survival rates and hazard ratio will be estimated along with 95% confidence intervals.
- Objective response [ Time Frame: Up to 5 years ]Will be assessed by RECIST version 1.1 criteria. Will be estimated using objective response rate where objective response rate is defined as the number of evaluable patients achieving a response (partial response or complete response per RECIST version 1.1) during treatment with study therapy divided by the total number of evaluable patients. Rates of response will be compared across arms using a Chi-Square Test for Proportion. Point estimates will be generated for objective response rates within each arm along with 95% binomial confidence intervals.
- Incidence of adverse events [ Time Frame: Up to 5 years ]Will be assessed per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The term toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Toxicities will be evaluated via the ordinal Common Terminology Criteria for Adverse Events standard toxicity grading. Similarly, scores (0-4) and the maximum score for each Patient-Reported Outcomes-CTCAE item will be recorded for each patient.
- Biochemical response [ Time Frame: Up to 5 years ]Levels of chromogranin A, urine and/or plasma catecholamines and metanephrines may predict response to therapy. The proportion of patients with a biochemical response of partial response or better, as determined by plasma and/or urine catecholamines and metanephrines, will be calculated, and a 95% confidence interval will be placed on this proportion. For each factor, we will calculate the mean +/- standard deviation, minimum, maximum, and quartiles; in addition, we will generate box and whisker plot.
- Biomolecular markers associated with clinical outcome [ Time Frame: Up to 5 years ]Will analyze for MGMT methylation expression in archival tumors and correlate with the radiographic response rate in metastatic pheochromocytoma/paraganglioma. This is hypothesis generated box and whisker plot.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04394858
|Principal Investigator:||Jaydira Del Rivero||Alliance for Clinical Trials in Oncology|