Olaparib + Sapacitabine for Breast Cancer

Not currently recruiting at 1 trial location

Overseen By Sara M. Tolaney, MD MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Pneumonitis, Hepatitis B/C, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 28

Duration: 28 days per cycle, up to 41 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, Olaparib (also known as Lynparza, a type of targeted cancer therapy) and Sapacitabine, to determine their effectiveness in treating breast cancer in patients with a BRCA gene mutation. The study aims to identify the optimal dose levels of these drugs when used together. Individuals with metastatic or hard-to-remove breast cancer and a known harmful BRCA mutation might be suitable candidates. Participants should have previously tried treatments like endocrine therapy or HER2-directed therapy that were unsuccessful. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must stop any endocrine therapy at least 7 days before starting the trial. Additionally, if you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them 2 to 5 weeks before the trial, depending on the specific medication.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of Olaparib and Sapacitabine has been studied for safety and effectiveness in treating breast cancer with a BRCA mutation. Previous studies found that this combination can be beneficial, with some patients experiencing improvements lasting over 15 months. These results suggest that many patients tolerate the treatment well.

Olaparib, one of the drugs in this combination, has been used alone in other studies and is known to be safe. It has shown benefits in extending patient survival and reducing the risk of cancer-related events. Sapacitabine has also been tested in different contexts and has proven safe when used with other treatments. While specific safety data for the combination of Olaparib and Sapacitabine is limited, the use of these drugs in other studies provides some reassurance about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for breast cancer, which often includes chemotherapy and hormone therapy, the combination of Olaparib and Sapacitabine offers a unique approach by targeting specific DNA repair mechanisms. Olaparib is a PARP inhibitor that helps prevent cancer cells from repairing their DNA, making them more susceptible to damage. Sapacitabine, on the other hand, introduces DNA damage, which complements Olaparib's action. Researchers are excited because this dual approach could potentially enhance the effectiveness of treatment by specifically targeting cancer cell vulnerabilities, leading to better outcomes with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for breast cancer with a BRCA mutation?

Research has shown that Olaparib, a PARP inhibitor, effectively treats breast cancer, particularly in patients with BRCA1/2 gene mutations. One study found that 87.5% of patients were still alive after six years, compared to 83.2% in the group not receiving Olaparib. Another study demonstrated that Olaparib reduced the risk of death by 32% in early-stage breast cancer. In this trial, participants will receive a combination of Olaparib and Sapacitabine at varying dose levels. Early results from 18 patients indicated that 89% experienced a positive tumor response after two months. These findings suggest that this combination could be a promising treatment for breast cancer with BRCA mutations. ^{2 3 5 6 7}

Who Is on the Research Team?

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with metastatic or unresectable breast cancer that has a BRCA mutation. Candidates must have progressed after certain therapies, depending on their cancer type. They should be able to take oral medication and agree to use effective contraception. People with recent treatments, active hepatitis or HIV, heart issues, prior PARP inhibitor treatment, MDS/AML history, major surgery complications within 2 weeks before the study start are excluded.

Inclusion Criteria

My organs and bone marrow are working well.

Ability to understand and willingness to sign an informed consent document

My cancer can be measured or seen on tests.

Exclusion Criteria

I have had more than 3 chemotherapy treatments for my cancer after it spread.

I do not have any uncontrolled illnesses.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Olaparib and Sapacitabine in 28-day cycles to evaluate safety and effectiveness

28 days per cycle, up to 41 months

Visits every 28 days for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Sapacitabine

Trial Overview

The study tests a combination of two drugs: Sapacitabine (CYC682) and Olaparib (Lynparza™), as potential treatments for breast cancer with BRCA mutations. It's structured in phases; phase I evaluates safety while phase II measures how well the disease responds according to RECIST criteria.

How Is the Trial Designed?

Group I: Dose Level 3: Sapacitabine (250 mg) + Olaparib (300 mg) Experimental Treatment 2 Interventions

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Group II: Dose Level 2: Sapacitabine (200 mg) + Olaparib (300 mg) Experimental Treatment 2 Interventions

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Group III: Dose Level 1: Sapacitabine (150 mg) + Olaparib (300 mg) Experimental Treatment 2 Interventions

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Group IV: Dose Level -1: Sapacitabine (100 mg) + Olaparib (300 mg) Experimental Treatment 2 Interventions

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Cyclacel Pharmaceuticals, Inc.

Industry Sponsor

Trials

20

Recruited

2,100+

Published Research Related to This Trial

The pharmacokinetic (PK) profile of olaparib in Chinese patients with advanced solid tumors is similar to that observed in Western and Japanese populations, confirming that the recommended dose of 300 mg twice daily is appropriate for this group.

When olaparib was combined with paclitaxel, there was a significant decrease in olaparib exposure, and while adverse events were rare, hematological side effects were more common in patients receiving the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of olaparib tablets as monotherapy and in combination with paclitaxel: results of a Phase I study in Chinese patients with advanced solid tumours. Yuan, P., Shentu, J., Xu, J., et al.[2020]

Olaparib, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

A phase II study of the PARP inhibitor olaparib confirmed its clinical benefits for cancer patients with inherited BRCA1 and BRCA2 mutations, particularly in advanced breast and ovarian cancers.

The study also provided evidence that olaparib is effective against pancreatic and prostate cancers, expanding its potential use in treating various cancer types associated with these genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib shows promise in multiple tumor types. [2014]

Olaparib, an oral PARP-inhibitor, significantly improves progression-free survival in HER2-negative advanced breast cancer patients with BRCA1/2 mutations compared to standard chemotherapy, based on a randomized Phase III trial.

The trial also indicated an overall survival benefit for patients who had not received prior chemotherapy for metastatic disease, highlighting olaparib's potential as an effective treatment option in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. Griguolo, G., Dieci, MV., Miglietta, F., et al.[2021]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

In a Phase I study involving 28 Japanese patients with advanced solid tumors, olaparib tablets at doses of 200 and 300 mg twice daily were found to be tolerable, with no dose-limiting toxicities reported.

The most common side effects included nausea, decreased appetite, anemia, and constipation, but no confirmed antitumor responses were observed, leading to the selection of 300 mg bid as the recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. Yonemori, K., Tamura, K., Kodaira, M., et al.[2022]

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