Skip to main content
MedPathMedPath Home
Clinical Trials/NCT05358639
NCT05358639
Active, not recruiting
Phase 1

A Phase I Trial of the Combination of Olaparib and Navitoclax in Women with High Grade Serous Epithelial Ovarian Cancer and Triple Negative Breast Cancer

Sunnybrook Health Sciences Centre3 sites in 1 country36 target enrollmentNovember 9, 2022
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
ConditionsHigh Grade Serous CarcinomaTriple Negative Breast CancerOvarian Cancer
InterventionsOlaparib tabletNavitoclax
DrugsOlaparib tabletNavitoclax

Overview

Phase
Phase 1
Intervention
Olaparib tablet
Conditions
High Grade Serous Carcinoma
Sponsor
Sunnybrook Health Sciences Centre
Enrollment
36
Locations
3
Primary Endpoint
To define a dose and schedule of navitoclax (Recommended Phase II Dose, RP2D) that can be combined safely with Olaparib in women with metastatic recurrent high grade serous ovarian cancer (HGSC) and triple negative breast cancer (TNBC) for further study
Status
Active, not recruiting
Last Updated
last year
OverviewInvestigatorsEligibility CriteriaArms & InterventionsOutcomesSitesSimilar TrialsRelated News

Overview

Brief Summary

The purpose of this Phase I study is to determine if the PARP inhibitor olaparib can be safely combined with navitoclax, an inhibitor of Bcl-2/Bcl-XL, in women with TNBC who have somatic or germline mutations in breast cancer gene one (BRCA1) and breast cancer gene two (BRCA2) BRCA1/2 or PALB2 and in women with recurrent HGSC who have progressed greater than 6 months since their last platinum containing chemotherapy. The trial is designed as an open- label multi-center Phase I interventional and translational study. It will identify the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D of olaparib combined with navitoclax for study in Phase II. There is a plan for a follow on Phase II study depending on the results obtained during this Phase I trial.The rationale for this study is that for a subset of patients, olaparib, will increase tumor cell survival dependence on inhibition of cell death by Bcl 2/Bcl- XL. Thus, navitoclax will augment apoptosis induced by PARP inhibition with olaparib.

Detailed Description

In this trial, olaparib will be delivered alone for 14 days with the hypothesis that priming of the apoptotic machinery will be required prior to introduction of the senolytic agent (navitoclax). To date navitoclax and olaparib have not been combined in the clinic. The Phase I study will therefore be conducted to define the recommended Phase II dose (RP2D). A plan for a future Phase II study will depend on the results obtained during this Phase I trial. Based on the potential for overlapping toxicity (particularly hematologic toxicity) an interrupted dosing schedule will be used for the navitoclax. Based on preclinical studies it is believed that intermittent delivery of the senolytic agent is in line with the proposed mechanism of action. Subsequently the dose of navitoclax will be escalated with a fixed dose of olaparib in 28-day cycles.

Registry
clinicaltrials.gov
Start Date
November 9, 2022
End Date
April 28, 2025
Last Updated
last year
Study Type
Interventional
Study Design
Single Group
Sex
Female

Investigators

Responsible Party
Sponsor

Eligibility Criteria

Inclusion Criteria

  • Not provided

Exclusion Criteria

  • Not provided

Arms & Interventions

Single

Olaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily (bid). Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated. Navitoclax will be administered daily. The initial dose of olaparib 200 mg has been selected after considering the single agent Phase I/II dose based and on ongoing combination studies on expected toxicity and evidence for reduced PARP inhibition

Intervention: Olaparib tablet

Single

Olaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily (bid). Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated. Navitoclax will be administered daily. The initial dose of olaparib 200 mg has been selected after considering the single agent Phase I/II dose based and on ongoing combination studies on expected toxicity and evidence for reduced PARP inhibition

Intervention: Navitoclax

Outcomes

Primary Outcomes

To define a dose and schedule of navitoclax (Recommended Phase II Dose, RP2D) that can be combined safely with Olaparib in women with metastatic recurrent high grade serous ovarian cancer (HGSC) and triple negative breast cancer (TNBC) for further study

Time Frame: 2 years

The RP2D will be determined based on an evaluation of multiple endpoints, which will include the DLT( dose limiting toxicity) rate.

Secondary Outcomes

  • Cmax: the maximum drug concentration.(2 years)
  • Tmax: time to reach the maximum drug concentration.(2 years)

Study Sites (3)

Loading locations...

Similar Trials

Terminated
Phase 2
Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate in Castration Resistant Prostate CancerProstate CancerCastration-resistant Prostate Cancer
NCT05501548Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins4
Recruiting
Phase 2
Olaparib in Combination With Pembrolizumab for Advanced Uveal MelanomaUveal MelanomaOcular Melanoma
NCT05524935H. Lee Moffitt Cancer Center and Research Institute37
Completed
Phase 2
Olaparib, Durvalumab, and Tremelimumab in Treating Patients With Recurrent or Refractory Ovarian, Fallopian Tube or Primary Peritoneal Cancer With BRCA1 or BRCA2 MutationBRCA1 Gene MutationBRCA2 Gene MutationOvarian Serous AdenocarcinomaRecurrent Fallopian Tube CarcinomaRecurrent Ovarian CarcinomaRecurrent Primary Peritoneal Carcinoma
NCT02953457Roswell Park Cancer Institute40
Active, not recruiting
Phase 1
Testing the Safety of Different Doses of Olaparib Given Radium-223 for Men With Advanced Prostate Cancer With Bone MetastasisCastration-Resistant Prostate CarcinomaMetastatic Prostate AdenocarcinomaStage IVB Prostate Cancer AJCC v8
NCT03317392National Cancer Institute (NCI)145
Active, not recruiting
Phase 1
Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast CancerBreast Cancer MetastaticBreast Cancer
NCT03742245The Methodist Hospital Research Institute28

Related News

Mitochondrial Priming Emerges as Key Determinant for CAR-T/NK Cell Immunosenolytic Therapy Success- Recent BH3 profiling studies reveal that therapy-induced senescent (TIS) cancer cells exhibit reduced overall mitochondrial priming compared to proliferating cells, challenging the prevailing assumption that senescent cells are universally primed for apoptosis. - BCL-xL emerges as a conserved anti-apoptotic dependency across different TIS models, with functional BH3 profiling serving as a predictive biomarker for senolytic drug selection and CAR-T/NK cell immunotherapy response. - Metabolic interventions that shift cellular metabolism from glycolysis to oxidative phosphorylation significantly enhance the efficacy of mitochondria-targeting senolytic therapies like ABT263 and ARV825 both in vitro and in vivo. - The "one-two punch" senogenic-immunosenolytic strategy represents a paradigm shift in cancer treatment, with precision BH3 profiling-guided approaches potentially transforming CAR-T/NK cells into personalized "living senolytics" for eliminating therapy-resistant cancer cells.