Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Breast Diseases

Skin Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Adenocarcinoma of the Appendix

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Navitoclax

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

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

Olaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily. Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated.

Olaparib tablet

For navitoclax, a lead-in of 7 days at 150 mg PO will be used prior to dose escalation. The DLT period for dose levels above DL 3 will include the 14-day olaparib alone lead-in, the 7 days combination with navitoclax at 150 mg and the first 28 day cycle of the combination of olaparib and navitoclax cycle at the full dose level dosing (49 days).

Helen Mackay

Helen MacKay, MD

Rossanna Pezo, MD

Katarzyna Jerzak, MD

Lilian Gien, MD

Stephanie Lheureux, MD

Neesha Dhani, MD

Gita Bhat, MD

Robert C. Grant, MD

Husam Ali Mahmoud Alqaisi, MD

Amit M. Oza, MD

Diane Provencher, MD

Annick Pina, MD

Beatrice Cormier, MD

Omar Moreira-Basha, MD

Thomas Warkus, MD

Vanessa Samouëlian, MD

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.

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.

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.

Combination of Olaparib and Navitoclax in Women With HGSC and TNBC

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

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

The maximum drug concentration will be measured in blood samples as part of the PK profile of olaparib and navitoclax when given in combination.

The time to reach maximum drug concentration will be measured in blood samples as part of the PK profile of olaparib and navitoclax when given in combination.

Exactis Innovation

Centre hospitalier de l'Université de Montréal (CHUM)

Princess Margaret Hospital, Canada

Sunnybrook Health Sciences Centre

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination of Olaparib and Navitoclax in Women With HGSC and TNBC	NCT05358639	High Grade Sero... Triple Negative... Ovarian Cancer	Olaparib tablet Navitoclax	18 Years -	Sunnybrook Health Sciences Centre
Combination of Olaparib and Navitoclax in Women With HGSC and TNBC	NCT05358639	High Grade Sero... Triple Negative... Ovarian Cancer	Olaparib tablet Navitoclax	18 Years -	Sunnybrook Health Sciences Centre
Combination of Olaparib and Navitoclax in Women With HGSC and TNBC	NCT05358639	High Grade Sero... Triple Negative... Ovarian Cancer	Olaparib tablet Navitoclax	18 Years -	Sunnybrook Health Sciences Centre

Spots Global Cancer Trial Database for bim

Every month we try and update this database with for bim cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bim

Every month we try and update this database with for bim cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bim cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.