Ignite Creation Date:
2025-12-24 @ 1:37 PM
Ignite Modification Date:
2025-12-27 @ 9:15 PM
Study NCT ID:
NCT03878095
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-11-17
First Post:
2019-03-15
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase II Study of Olaparib and AZD6738 in Isocitrate Dehydrogenase (IDH) Mutant Solid Tumors
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 or unacceptable toxicity. 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.
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 or unacceptable toxicity. 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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: