Olaparib, Durvalumab, and Tremelimumab in Treating Patients With Recurrent or Refractory Ovarian, Fallopian Tube or Primary Peritoneal Cancer With BRCA1 or BRCA2 Mutation
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|ClinicalTrials.gov Identifier: NCT02953457|
Recruitment Status : Active, not recruiting
First Posted : November 2, 2016
Results First Posted : October 5, 2022
Last Update Posted : October 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|BRCA1 Gene Mutation BRCA2 Gene Mutation Ovarian Serous Adenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma||Biological: Durvalumab Other: Laboratory Biomarker Analysis Drug: Olaparib Biological: Tremelimumab||Phase 2|
I. To assess the safety and toxicity of the combination of PARP inhibitor olaparib with anti-PD-L1 antibody durvalumab and anti-CTLA4 antibody tremelimumab. (Phase I) II. To assess the impact of the combination of olaparib with durvalumab and tremelimumab on progression free survival (PFS) rates. (Phase II)
I. To assess the impact of the combination of olaparib with durvalumab and tremelimumab on anti-tumor immune responses in patients with recurrent platinum sensitive or resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer who carry a germline and/or somatic BRCA1 or BRCA2 mutation and/or a homologous recombination deficiency (HRD).
II. To assess the impact of the combination of olaparib with durvalumab and tremelimumab on PFS and overall survival (OS) in patients with recurrent platinum sensitive or resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer who carry a germline and/or somatic BRCA1 or BRCA2 mutation and/or a HRD.
OUTLINE: This is a phase I, dose-escalation study of olaparib followed by a phase II study.
Patients receive olaparib orally (PO) twice daily (BID), and tremelimumab intravenously (IV) over 1 hour and durvalumab IV over 1 hour on day 1. Treatment with olaparib continues for up to 12 months in the absence of disease progression or unacceptable toxicity. Treatment with tremelimumab repeats every 4 weeks for up to 4 courses and treatment with durvalumab repeats every 4 weeks for up to 13 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, and every 2 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Evaluation of Olaparib in Combination With Durvalumab (Medi4736) and Tremelimumab in the Treatment of Recurrent Platinum Sensitive or Resistant or Refractory Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Patients Who Carry a BRCA1 or BRCA2 Mutation|
|Actual Study Start Date :||June 29, 2017|
|Actual Primary Completion Date :||September 15, 2021|
|Estimated Study Completion Date :||December 15, 2022|
Experimental: Treatment (olaparib, tremelimumab, durvalumab)
Patients receive olaparib PO BID, and tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1. Treatment with olaparib continues for up to 12 months in the absence of disease progression or unacceptable toxicity. Treatment with tremelimumab repeats every 4 weeks for up to 4 courses and treatment with durvalumab repeats every 4 weeks for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of Dose-limiting Toxicities (DLTs) Defined as the Rate of Drug-related Grade 3-5 Adverse Events Assessed Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (Phase I) [ Time Frame: Up to 8 weeks ]The maximum tolerated dose is defined as the highest dose studied, for which the observed incidence of DLT is less than 33%. Number of Participants with Dose-limiting Toxicities (DLTs) in Phase I and Phase II will be reported.
- 3 Month Progression Free Survival (PFS) in the All Eligible Patients by Group/Arm [ Time Frame: At 3 months ]Progression free survival (PFS) rate will be assessed at 3 months in the platinum resistant group using Kaplan-Meier methods. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- 6 Month Progression Free Survival (PFS) in the Platinum Sensitive Group (Phase II) [ Time Frame: At 6 months ]6-month progression-free survival rate is the probability of patients remaining alive and progression-free at 6 months from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesion
- Anti-tumor Immune Response of the Treatment Combination Assessed in Tumor Biopsy [ Time Frame: At 12 weeks ]Tumor biopsy samples will be examined to evaluate the correlation between clinical activity and the expression level of PD-L1 and tumor-infiltrating lymphocytes changes in biopsies pre and post treatment.
- Overall Survival (OS) [ Time Frame: 35 months ]OS will be summarized and analyzed descriptively via summary frequencies and Kaplan-Meier estimators.
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): NCT02953457
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|The Feinstein Institute for Medical Research/Lennox Hill Hospital|
|New York, New York, United States, 10075|
|Principal Investigator:||Emese Zsiros||Roswell Park Cancer Institute|