Olaparib + Sapacitabine for Breast Cancer

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

10 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Olaparib and Sapacitabine for breast cancer?

Olaparib has shown effectiveness in treating certain types of breast cancer, particularly in patients with specific genetic mutations (BRCA1/2) and HER2-negative breast cancer, by improving progression-free survival compared to standard chemotherapy. It is also approved for use in high-risk early breast cancer with BRCA mutations. ^{1 2 3 4 5}

Is the combination of Olaparib and Sapacitabine safe for humans?

Olaparib (also known as Lynparza) has been studied for safety in various cancers, including breast cancer, and is generally considered to have a manageable safety profile. It has been tested in different populations and shown to be safe when used alone or with other treatments, but specific safety data for the combination with Sapacitabine is not available in the provided research. ^{1 2 6 7 8}

How is the drug combination of Olaparib and Sapacitabine unique for treating breast cancer?

The combination of Olaparib and Sapacitabine is unique because Olaparib is a PARP inhibitor that targets cancer cells with BRCA mutations, which are common in certain types of breast cancer, while Sapacitabine is being explored for its potential to enhance the effects of Olaparib. This combination aims to improve outcomes in patients with specific genetic profiles, offering a personalized treatment approach. ^{1 2 4 9 10}

What is the purpose of this trial?

This research study is studying a combination of drugs as a possible treatment for breast cancer with a BRCA mutation. The interventions involved in this study are: * Sapacitabine (CYC682) * Olaparib (Lynparza™)

Research Team

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

My cancer can be measured or seen on tests.

Ability to understand and willingness to sign an informed consent document

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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 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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

3. Japan pubmed.ncbi.nlm.nih.gov

Antitumor and anticancer stem cell activity of a poly ADP-ribose polymerase inhibitor olaparib in breast cancer cells. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Olaparib shows promise in multiple tumor types. [2014]

7. Germany 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. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

10. England 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. [2022]