Olaparib + Navitoclax for Breast Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores whether two drugs, olaparib (also known as Lynparza, a type of targeted therapy) and navitoclax, can effectively treat breast cancer together. Researchers are focusing on women with triple-negative breast cancer (TNBC) or high-grade serous carcinoma (HGSC) who have specific genetic mutations and whose cancer has progressed after chemotherapy. The goal is to identify a safe and effective dose combination for future studies. This trial may suit women whose breast cancer has specific gene mutations (such as BRCA1 or BRCA2) and has worsened after previous treatments, but who can still take the medications orally. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.
Will I have to stop taking my current medications?
You may need to stop taking certain medications before joining the trial. Specifically, you cannot take certain blood thinners or medications that affect platelet function within 14 days before starting the trial drugs. It's best to discuss your current medications with the trial team to see if any changes are needed.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research shows that olaparib is generally well-tolerated by patients with BRCA-mutated breast cancer. Studies have found that it does not cause increasing side effects over time, even with long-term use. Patients in these studies lived longer, and most side effects were manageable.
Safety studies indicate that navitoclax can be safely used with other cancer treatments. Some patients experienced reduced bone marrow activity, which limited the dose. Overall, navitoclax showed promising effects against tumors.
In summary, both olaparib and navitoclax have been studied separately and found to be generally safe, with some manageable side effects. This trial aims to find a safe way to use them together, making close monitoring of safety important.12345Why are researchers excited about this trial's treatments?
Researchers are excited about the combination of olaparib and navitoclax for breast cancer because it offers a novel approach compared to traditional treatments like chemotherapy and hormone therapy. Olaparib is a PARP inhibitor, which works by blocking a protein that cancer cells need to repair their DNA, causing them to die. Navitoclax enhances this effect by inhibiting proteins that prevent cancer cell death, potentially leading to more effective treatment outcomes. This combination targets cancer cells in two unique ways, offering hope for improved results over existing therapies.
What evidence suggests that the combination of olaparib and navitoclax could be effective for breast cancer?
Research has shown that olaparib helps patients with certain breast cancer genes, such as BRCA1 and BRCA2, live longer without their cancer worsening. In studies, olaparib reduced the risk of cancer progression or death by 32% compared to standard treatments.
Navitoclax aids in killing cancer cells and has slowed tumor growth, especially when combined with other drugs. While navitoclax alone may not always destroy cancer cells, it becomes more effective when used with other treatments.
In this trial, participants will receive a combination of olaparib and navitoclax. This combination could be more powerful because olaparib makes cancer cells more dependent on navitoclax, enhancing the overall treatment effect.56789Who Is on the Research Team?
Helen MacKay, MD
Principal Investigator
Sunnybrook Cancer Centre
Are You a Good Fit for This Trial?
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.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Olaparib is administered alone for 14 days, followed by continuous administration with escalating doses of navitoclax in 28-day cycles
Dose Escalation
Navitoclax dose is escalated with a fixed dose of olaparib to determine the recommended Phase II dose (RP2D)
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Navitoclax
- Olaparib
Trial Overview
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.
How Is the Trial Designed?
1
Treatment groups
Experimental Treatment
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
Find a Clinic Near You
Who Is Running the Clinical Trial?
Sunnybrook Health Sciences Centre
Lead Sponsor
Princess Margaret Hospital, Canada
Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborator
Exactis Innovation
Collaborator
Citations
Navitoclax enhances the effectiveness of EGFR-targeted ...
Treatment with navitoclax plus ABT-414 caused a significant reduction in tumor growth in five of seven PDXs and significant tumor regression in ...
Multi-Omics Investigation of Innate Navitoclax Resistance in ...
The breast cancer subtype with the least therapeutic options and therefore the poorest outcome is triple-negative breast cancer (TNBC) [20].
Combination of palbociclib with navitoclax based-therapies ...
In the case of breast cancer, navitoclax is not sufficient to induce tumour death in some breast cancer cell lines [60], as we have also observed in MDA-MB-231 ...
Clinical Review: Navitoclax as a Pro-Apoptotic and Anti ...
Navitoclax has been demonstrated as a single agent or in combination with other drugs to successfully ameliorate tumor progression and fibrosis development.
Human breast cancer cells display different sensitivities to ...
These data indicate that navitoclax induces cell death in MDA-MB-231 cells ... The sensitivity of both cell lines to navitoclax demonstrates breast cancer ...
Phase 1 Study of the Safety, Pharmacokinetics, and ...
Responses were assessed while patients continued treatment with navitoclax. Statistical Analysis. Safety data were summarized by navitoclax dose level.
Full article: A Phase I Study of the Safety, Pharmacokinetics ...
Navitoclax 150-mg orally once/day was safely administered with docetaxel. Myelosuppression limited dose escalation; antitumor activity was observed.
NCT01989585 | Testing the Addition of Navitoclax to ...
Because no dosing or adverse event data are currently available on the use of navitoclax in combination with dabrafenib and trametinib in ...
9.
breast-cancer-research.biomedcentral.com
breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-020-01374-8Navitoclax enhances the effectiveness of EGFR-targeted ...
Navitoclax enhances the effectiveness of EGFR-targeted antibody-drug conjugates in PDX models of EGFR-expressing triple-negative breast cancer.
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