NCT05358639

Combination of Olaparib and Navitoclax in Women with HGSC and TNBC

Active, enrolled Phase 1 Last updated 18 November 2024

What this trial tests

Phase 1 trial testing Olaparib tablet in High Grade Serous Carcinoma in 36 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

9 November 2022

Primary endpoint
30 March 2025

28 April 2025

Quick facts

Lead sponsor	Sunnybrook Health Sciences Centre
Phase	Phase 1
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	36
Start date	9 November 2022
Primary completion	30 March 2025
Estimated completion	28 April 2025
Sites	3 locations across Canada

Drugs / interventions tested

• Olaparib tablet — full drug profile →
• Navitoclax — full drug profile →

Conditions studied

• High Grade Serous Carcinoma — all drugs for High Grade Serous Carcinoma →
• Triple Negative Breast Cancer — all drugs for Triple Negative Breast Cancer →
• Ovarian Cancer — all drugs for Ovarian Cancer →

Sponsor

Sunnybrook Health Sciences Centre — full company profile →

Who can join

18 and older, female only, with High Grade Serous Carcinoma or Triple Negative Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
   Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
2. Targeting senescence as an anticancer therapy.
   Bousset L, Gil J. · · 2022 · cited 70× · PMID 36065138 · DOI 10.1002/1878-0261.13312
3. Therapeutic strategies targeting cellular senescence for cancer and other diseases.
   Wang X, Fukumoto T, Noma KI. · · 2024 · cited 14× · PMID 38366629 · DOI 10.1093/jb/mvae015
4. Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.
   Peng M, Li N, Wang H, Li Y, et al · · 2025 · cited 12× · PMID 40717900 · DOI 10.1002/mco2.70304
5. SMARCA4 regulates the NK-mediated killing of senescent cells.
   Reen V, D'Ambrosio M, Søgaard PP, Tyson K, et al · · 2025 · cited 10× · PMID 39813356 · DOI 10.1126/sciadv.adn2811
6. Bcl-2 dependent modulation of Hippo pathway in cancer cells.
   D'Aguanno S, Brignone M, Scalera S, Chiacchiarini M, et al · · 2024 · cited 8× · PMID 38755629 · DOI 10.1186/s12964-024-01647-1
7. Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies.
   López J, Llop-Hernández À, Verdura S, Serrano-Hervás E, et al · · 2025 · cited 7× · PMID 40055336 · DOI 10.1038/s41420-025-02379-y
8. The Role of TRAIL Signaling in Cancer: Searching for New Therapeutic Strategies.
   Luo C, He S, Shi F, Zhou J, et al · · 2024 · cited 7× · PMID 39056714 · DOI 10.3390/biology13070521