NCT03878095

Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors

A Phase II Study of Olaparib and AZD6738 in Isocitrate Dehydrogenase (IDH) Mutant Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (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 and ceralasertib (AZD6738) work in treating patients with IDH mutant cholangiocarcinoma or solid tumors. Cancer is caused by changes (mutations) to genes that control the way cells function. Laboratory studies have shown that olaparib and AZD6738 can shrink IDH mutant tumors or stop them from growing. Olaparib and ceralasertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the overall response rates of olaparib and ceralasertib (AZD6738) in subjects with recurrent/progressive IDH1/2-mutant solid malignant tumors, who will be recruited to 2 cohorts: Ia. Cholangiocarcinoma (cohort has been closed to accrual); Ib. Other solid malignant tumors. SECONDARY OBJECTIVES: I. To assess the progression free survival (PFS) of olaparib and AZD6738 in adults with recurrent/progressive IDH1/2-mutant solid malignant tumors. II. To estimate the overall survival (OS) in adults with recurrent/progressive IDH1/2- mutant solid malignant tumors. III. To assess the duration of response in adults with recurrent/progressive IDH1/2-mutant solid malignant tumors. IV. To assess the safety and tolerability of the combination of olaparib and AZD6738. EXPLORATORY OBJECTIVES: I. To evaluate 2-hydroxyglutarate (2HG) concentration in plasma by mass spectrometry and correlate with treatment response. II. To evaluate 2HG levels in tumor biopsies prior to the beginning of treatment and while on therapy and correlate with treatment response. III. Correlate 2HG concentration in plasma and in tumor biopsies. IV. To evaluate deoxyribonucleic acid (DNA) double strand breaks (DSBs) as measured by mass cytometry time of flight (CyTOF)-imaging mass cytometry (IMC) in tumor biopsies before and after treatment with olaparib and AZD6738. OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28 of each cycle and ceralasertib PO once daily (QD) on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression, unacceptable toxicity, withdrawal of consent or death. Patients also undergo tumor biopsies during screening and on study, collection of blood samples throughout the trial, and undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) scans throughout the trial. Patients may also undergo bone marrow aspiration and biopsy as clinically indicated on study. After completion of study treatment, patients are followed up for 30 days.

Conditions

• Malignant Solid Neoplasm
• Refractory Cholangiocarcinoma
• Refractory Malignant Solid Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tumor biopsies
PROCEDURE	Biospecimen Collection	Undergo collection of blood
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
DRUG	Ceralasertib	Given PO
PROCEDURE	Computed Tomography	Undergo CT scans
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI scans
DRUG	Olaparib	Given PO

Timeline

• Start date: 2020-01-30
• Primary completion: 2025-03-12
• Completion: 2026-07-10
• First posted: 2019-03-18
• Last updated: 2026-04-08
• Results posted: 2026-04-08

Locations

13 sites across 1 country: United States

Regulatory

• FDA-regulated drug study