NCT04394858|Active Not RecruitingPhase 2FDA Drug

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

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2020-03379A021804U10CA180821

Study Type

interventional

Target

Locations

1 country

Sites

163

Timeline

RegisteredMay 2020

StartedMar 2021

CompletionMar 2028

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

22mo left

Started Mar 2021

Longer than P75 for phase_2

Geographic Reach

1 country

163 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7 years study duration

Study Progress74%

Mar 2021Mar 2028

First Submitted

Initial submission to the registry

May 19, 2020

Completed

1 day until next milestone

First Posted

Study publicly available on registry

May 20, 2020

Completed

10 months until next milestone

Study Start

First participant enrolled

March 17, 2021

Completed

7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2028

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2028

Last Updated

April 13, 2026

Status Verified

March 1, 2026

Enrollment Period

7 years

First QC Date

May 19, 2020

Last Update Submit

April 9, 2026

Conditions

Stage IV Adrenal Gland Pheochromocytoma and Sympathetic Paraganglioma AJCC v8 Unresectable Paraganglioma Advanced Adrenal Gland Pheochromocytoma Advanced Paraganglioma Metastatic Adrenal Gland Pheochromocytoma Metastatic Paraganglioma Stage III Adrenal Gland Pheochromocytoma and Sympathetic Paraganglioma AJCC v8 Unresectable Adrenal Gland Pheochromocytoma

Outcome Measures

Primary Outcomes (1)

Progression-free survival (PFS)
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.
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

Secondary Outcomes (3)

Overall survival (OS)
From randomization to death due to any cause, assessed up to 5 years
Objective response
Up to 5 years
Incidence of adverse events
Up to 5 years

Other Outcomes (2)

Biochemical response
Up to 5 years
Biomolecular markers associated with clinical outcome
Up to 5 years

Study Arms (2)

Arm I (temozolomide, olaparib)

EXPERIMENTAL

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. 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.

Procedure: Biospecimen CollectionProcedure: Computed Tomography with ContrastProcedure: Magnetic Resonance ImagingDrug: OlaparibOther: Quality-of-Life AssessmentDrug: Temozolomide

Arm II (temozolomide)

ACTIVE COMPARATOR

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.

Procedure: Biospecimen CollectionProcedure: Computed Tomography with ContrastProcedure: Magnetic Resonance ImagingOther: Quality-of-Life AssessmentDrug: Temozolomide

Interventions

Biospecimen CollectionPROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (temozolomide, olaparib)Arm II (temozolomide)

OlaparibDRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Arm I (temozolomide, olaparib)

Computed Tomography with ContrastPROCEDURE

Undergo CT with contrast

Also known as: Contrast Enhanced Computed Tomography, CONTRAST ENHANCED CT SCAN, Contrast-enhanced Computed Tomography, CT Scan With Contrast, CT with Contrast

Arm I (temozolomide, olaparib)Arm II (temozolomide)

Magnetic Resonance ImagingPROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm I (temozolomide, olaparib)Arm II (temozolomide)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (temozolomide, olaparib)Arm II (temozolomide)

TemozolomideDRUG

Given PO

Also known as: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temizole, Temodal, Temodar, Temomedac, TMZ

Arm I (temozolomide, olaparib)Arm II (temozolomide)

Eligibility Criteria

Age12 Years+

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

Documentation of disease
Histologic documentation: Histologically-proven advanced (metastatic or unresectable primary) pheochromocytoma or paraganglioma
Stage: Advanced (metastatic or unresectable primary) disease
Tumor site: Histologically-proven pheochromocytoma or paraganglioma
Radiographic evaluation: Radiographic evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 in the 12 months prior to registration
Measurable disease
Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 1 cm with CT or MRI (or \>= 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung
Prior treatment with other somatostatin analog, chemotherapy, radiotherapy (including peptide radionuclide receptor therapy \[PRRT\]), or surgery must be completed \>= 28 days prior to registration. Patients must have recovered from any effects of any major surgery prior to registration
Prior treatment with radiolabeled metaiodobenzylguanidine (MIBG) must be completed \>= 12 weeks prior to registration and lifetime cumulative 131I-MIBG dose must be \< 1000 MBq kg\^-1 (36 mCi kg\^-1)
Prior treatment with antibiotics must be completed \>= 7 days prior to registration
No prior treatment with temozolomide, dacarbazine, or a poly ADP ribose polymerase (PARP) inhibitor
No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required
Contraception
Therapy utilized in this trial is associated with medium/high fetal risk
+31 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (163)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC