NCT03212274

Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations

A Phase 2 Study of the PARP Inhibitor Olaparib (AZD2281) in IDH1 and IDH2 Mutant Advanced Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 89 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that has spread from where it first started (primary site) to other places in the body (metastatic) and that does not respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVE: I. To estimate the overall response rates of olaparib in subjects with recurrent/progressive IDH1/2-mutant solid tumors, who will be recruited to 3 cohorts: a. glioma, b. cholangiocarcinoma, c. other solid malignant tumors. SECONDARY OBJECTIVES: I. To estimate the distribution of progression free survival (PFS) of olaparib in adults with recurrent/progressive IDH1/2-mutant glioma and cholangiocarcinoma. II. To estimate the overall survival (OS) in adults with recurrent/progressive IDH1/2- mutant glioma and cholangiocarcinoma. III. To determine the duration of response in adults with recurrent/progressive IDH1/2-mutant glioma, cholangiocarcinoma or other solid malignant tumors. IV. To confirm the safety and tolerability of olaparib monotherapy. EXPLORATORY OBJECTIVES: I. To describe 2HG concentration in plasma by mass spectrometry at baseline and at specific timepoints and correlate with treatment response. II. To describe 2HG levels in tumor biopsies from prior to the beginning of treatment and at specific timepoints and correlate with treatment response. III. To evaluate in tumor biopsies and in liquid biopsies performed at baseline and at specific timepoints if co-occurring alterations detected via multiplexed immunofluorescence, mass cytometry (CyTOF)-imaging mass cytometry (IMC), ribonucleic acid (RNA) sequencing and/or deoxyribonucleic acid (DNA) sequencing can be associated with differential levels of 2HG production, treatment response and resistance. OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression, unacceptable toxicity, withdrawal of consent or death. Patients undergo a computer tomography (CT) scan and/or magnetic resonance imaging (MRI), as well as a tumor biopsy and blood sample collection on study. After completion of study treatment, patients are followed up for 30 days.

Conditions

• Advanced Malignant Solid Neoplasm
• Glioblastoma
• Recurrent Cholangiocarcinoma
• Recurrent Glioma
• Recurrent Malignant Solid Neoplasm
• WHO Grade 2 Glioma
• WHO Grade 3 Glioma

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo a CT scan
PROCEDURE	Magnetic Resonance Imaging	Undergo a MRI
DRUG	Olaparib	Given PO

Timeline

• Start date: 2019-01-30
• Primary completion: 2025-04-02
• Completion: 2026-07-28
• First posted: 2017-07-11
• Last updated: 2026-02-19

Locations

51 sites across 1 country: United States

Regulatory

• FDA-regulated drug study