What side effects are associated with this type of intervention?

Olaparib, a PARP inhibitor, commonly causes side effects such as anemia, nausea, fatigue, and vomiting. Navitoclax, a Bcl-2/Bcl-XL inhibitor, is still under investigation, but similar agents often cause hematologic toxicities like thrombocytopenia. Other common treatments for ovarian cancer, such as platinum-based chemotherapy, can lead to neutropenia, thrombocytopenia, anemia, and non-hematologic toxicities like nausea and fatigue. Angiogenesis inhibitors like bevacizumab may cause hypertension, proteinuria, and increased risk of bleeding.

What prior FDA approvals exist?

The FDA has approved several PARP inhibitors for the treatment of ovarian cancer, including Olaparib, Niraparib, and Rucaparib. These drugs are primarily used as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer and have demonstrated improvements in progression-free survival (PFS). Olaparib, in particular, has been studied extensively and is effective in both BRCA-mutated and non-BRCA-mutated ovarian cancers. Additionally, Bevacizumab, an angiogenesis inhibitor, is approved for use in combination with platinum-based chemotherapy followed by maintenance therapy in platinum-sensitive ovarian cancer. These treatments aim to prolong the period of remission and improve overall outcomes for patients.

What other types of research exist?

Promising alternatives to Olaparib and Navitoclax for ovarian cancer patients include other PARP inhibitors such as Rucaparib and Niraparib, which have shown high efficacy in improving progression-free survival (PFS) in patients with BRCA mutations and homologous recombination deficiency (HRD). Additionally, combination therapies involving targeted agents like Venetoclax (Bcl-2 inhibitor) with other chemotherapeutic or targeted agents may offer novel treatment options. Clinical trials exploring these combinations and other emerging therapies should be considered.

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Bcl-2/Bcl-XL Inhibitor

Olaparib + Navitoclax for Breast Cancer

Phase 1

Recruiting

Led By Helen MacKay, MD

Research Sponsored by Sunnybrook Health Sciences Centre

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

No more than two (2) prior lines of treatment for TNBC

Metastatic TNBC with known deleterious somatic or germline mutations in BRCA1, BRCA2, or PALB2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, olaparib and navitoclax, in women with specific genetic mutations in aggressive breast and ovarian cancers. Olaparib weakens the cancer cells, and navitoclax helps kill them. The goal is to find a safe and effective dose for future studies. Olaparib has been approved for use in patients with advanced ovarian cancer.

Who is the study for?

This trial is for women over 18 with certain types of advanced ovarian or breast cancer (HGSC, TNBC) who have specific genetic mutations (BRCA1/2, PALB2). They should not have had more than two treatments for TNBC and must be able to take oral medications. Women must not be pregnant and should have a life expectancy of at least 16 weeks.

What is being tested?

The study tests combining Olaparib, a PARP inhibitor, with Navitoclax, which blocks proteins that prevent cell death in cancers like HGSC and TNBC. It aims to find the safest dose combination for future Phase II trials by observing side effects and determining the maximum tolerated dose.

What are the potential side effects?

Possible side effects include nausea, fatigue, anemia (low red blood cells), risk of bleeding or bruising due to low platelets, gastrointestinal issues affecting absorption of the drugs, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had no more than two treatments for triple-negative breast cancer.

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My triple-negative breast cancer has harmful mutations in BRCA1, BRCA2, or PALB2.

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I am 18 years old or older.

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I can swallow pills and don't have stomach issues affecting medicine absorption.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

Cmax: the maximum drug concentration.

Tmax: time to reach the maximum drug concentration.

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: SingleExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Navitoclax

2012

Completed Phase 2

~120

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

PARP inhibitors, such as Olaparib, work by blocking the PARP enzyme, which is crucial for repairing single-strand DNA breaks. In cancer cells with BRCA1/2 mutations, this leads to the accumulation of DNA damage and ultimately cell death, a concept known as synthetic lethality. Bcl-2/Bcl-XL inhibitors like Navitoclax promote cancer cell death by inhibiting proteins that prevent apoptosis, the programmed cell death process. Combining these treatments can enhance the effectiveness of inducing cancer cell death, offering a promising approach for patients with ovarian cancer, particularly those with specific genetic mutations.

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer.PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.