Olaparib for Ovarian and Peritoneal Cancer

Overseen By Shannon N Westin

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Other cancer, Cardiac conditions, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This early phase I trial studies how well olaparib works in treating patients with newly diagnosed BRCA-mutant ovarian, primary peritoneal, or fallopian cancer before surgery. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications that are strong or moderate CYP3A inhibitors or inducers. There is a washout period (time without taking these medications) of 2 weeks for inhibitors and up to 5 weeks for some inducers before starting olaparib.

Is olaparib safe for treating ovarian and peritoneal cancer?

Olaparib, also known as Lynparza, is generally well tolerated in patients with ovarian cancer, with most side effects being mild to moderate. Common severe side effects include fatigue, anemia (low red blood cell count), and neutropenia (low white blood cell count), but these do not usually require stopping the treatment. ^{1 2 3 4 5}

How is the drug olaparib unique in treating ovarian and peritoneal cancer?

Olaparib is unique because it is an oral drug specifically designed for patients with BRCA mutation-positive ovarian cancer, acting as a personalized therapy by inhibiting a protein called PARP, which helps repair damaged DNA in cancer cells. This drug is used as maintenance therapy after chemotherapy to prolong the period before the cancer progresses, especially in those who have responded well to platinum-based chemotherapy. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Olaparib for ovarian and peritoneal cancer?

Research shows that Olaparib, a drug used for ovarian cancer, significantly improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in patients with BRCA mutations and those who have responded to platinum-based chemotherapy. It is effective as a maintenance therapy, helping to keep the cancer from progressing after initial treatment. ^{1 2 3 4 5}

Who Is on the Research Team?

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with newly diagnosed BRCA-mutant ovarian, primary peritoneal, or fallopian cancer who haven't had surgery yet. Eligible participants must have good blood counts and organ function, be able to perform daily activities with ease or only slight limitation (ECOG 0-1), and not be pregnant. They shouldn't have received prior treatment for these cancers or any PARP inhibitors like olaparib.

Inclusion Criteria

Your liver enzyme levels must be within a certain range, unless you have cancer that has spread to the liver.

Your bilirubin level in the blood is not more than 1.5 times the normal limit.

Written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations

Exclusion Criteria

My cancer is either mucinous or a low-grade epithelial type.

I have received treatment for ovarian, fallopian tube, or peritoneal cancer.

I am not able to participate in the study's surveys because I do not speak English.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib orally twice daily on days 1-28, repeated every 28 days for up to 2 cycles

8 weeks

Surgery and Chemotherapy

Participants undergo surgery and receive standard chemotherapy for up to 4 cycles, or receive chemotherapy first then undergo surgery

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Olaparib
• Therapeutic Conventional Surgery

Trial Overview The trial is testing the effectiveness of Olaparib before surgery in stopping tumor growth in patients with specific types of cancer linked to BRCA mutations. It's an early phase I study which means it's one of the first times this approach is being tried out to see how well it works and how safe it is.

How Is the Trial Designed?

Group I: Treatment (olaparib) Experimental Treatment 3 Interventions

Patients receive olaparib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After treatment, patients either undergo surgery then receive standard chemotherapy for up to 4 cycles or receive standard chemotherapy within 14 days for up to 4 cycles then undergo surgery in the absence of disease progression or unacceptable toxicity at the discretion of the treating physician.

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Olaparib is an effective first-line maintenance treatment for adults with advanced ovarian cancer who have responded to platinum-based chemotherapy, significantly improving progression-free survival compared to placebo in phase III trials.

When combined with bevacizumab, olaparib further enhances treatment efficacy in patients with homologous recombination deficiency (HRD), but does not show benefits in HRD-negative tumors, indicating its targeted effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Paik, J.[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]

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

Citations

1. France pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]

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

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

3. 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]

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

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. [2016]