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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well the drug olaparib (Lynparza) treats newly diagnosed ovarian, primary peritoneal, or fallopian cancer with a specific genetic mutation known as BRCA. The researchers aim to determine if olaparib can stop cancer cells from growing by blocking certain enzymes before surgery. Participants will take olaparib in 28-day cycles and then receive chemotherapy (cytotoxic therapy) before or after surgery, depending on their response. This trial may suit those who have not received prior treatment for advanced ovarian or related cancers and have a confirmed BRCA mutation. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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

Research shows that olaparib is usually well-tolerated, but it can have serious side effects. In a study with patients who have advanced ovarian cancer, about 1.9% of those taking olaparib developed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), serious bone marrow issues. This compares to 0.8% of patients not taking olaparib.

Another study found that two-thirds of patients taking olaparib with another drug did not experience cancer growth or return, suggesting the drug's effectiveness. However, awareness of the potential risks is important.

Since this trial is in an early phase, it primarily aims to find the right dose and gather initial safety information. Researchers are closely monitoring the side effects of olaparib. Prospective participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for ovarian cancer?

Olaparib is unique because it targets cancer cells differently than traditional chemotherapy. Most treatments for ovarian and peritoneal cancer focus on killing rapidly dividing cells indiscriminately, which includes healthy cells. But Olaparib is a PARP inhibitor, which specifically disrupts the DNA repair process in cancer cells, causing them to die while sparing healthy cells. Researchers are excited about Olaparib because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes for patients.

What evidence suggests that olaparib might be an effective treatment for ovarian and peritoneal cancer?

Research has shown that olaparib, which participants in this trial may receive, can help treat ovarian cancer, especially in individuals with specific genetic changes like BRCA mutations. One study found that 67% of patients taking olaparib with bevacizumab did not experience cancer growth or recurrence, compared to only 30% of those taking a placebo. Other studies have found that olaparib can significantly extend the time patients live without their cancer worsening. This drug blocks certain proteins that cancer cells need to grow. Overall, these findings suggest that olaparib could be a strong option for treating ovarian cancer. ^{2 6 7 8 9}

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.

I am set to start chemotherapy before surgery to shrink my tumor after 3 cycles.

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 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]

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]

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 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]

Citations

1. lynparza.com lynparza.com/ovarian-cancer/results/advanced-ovarian-cancer.html

Results of LYNPARZA: advanced ovarian cancer 168 out of 255 patients on LYNPARZA + bevacizumab did not see their cancer grow or return compared with 40 out of 132 patients on bevacizumab + placebo. 67%.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8921481/

Systematic Review of Olaparib in the Treatment ... The results showed that HR = 1.24 (95%CI = 1.06-1.45, P = 0.006), suggesting that Olaparib can significantly prolong OS in patients with ovarian cancer, as ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01549

Overall Survival With Maintenance Olaparib at a 7-Year ... Maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly ...

4. onclive.com onclive.com/view/olaparib-withstands-the-test-of-time-with-long-term-data-supporting-its-role-in-ovarian-cancer-treatment

Olaparib Withstands the Test of Time With Long-Term Data ... The primary outcome was progression-free survival [PFS], and for women randomized to olaparib, the chances of progression or death were reduced ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S092375342404907X

Efficacy of subsequent therapies in patients with advanced ... In patients whose tumors tested HRD-positive, a clinically meaningful improvement in OS was observed in the olaparib plus bevacizumab arm versus the placebo ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40300425/

Final overall survival results from the OPINION trial Objective: Maintenance olaparib demonstrated clinical activity for progression-free survival in patients without a germline BRCA1 and/or BRCA2 mutation (non- ...

7. lynparzahcp.com lynparzahcp.com/

LYNPARZA® (olaparib) PARP Inhibitor | HCP site In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who received LYNPARZA and 0.8% (1/ ...

8. merck.com merck.com/news/lynparza-olaparib-in-combination-with-bevacizumab-and-as-monotherapy-demonstrates-clinically-meaningful-long-term-survival-in-certain-patients-with-first-line-advanced-ovarian-cancer-in-expl/

LYNPARZA® (olaparib) in Combination With ... - Merck.com In the trial, LYNPARZA demonstrated a clinically meaningful improvement in OS versus placebo in patients with germline BRCA-mutated (gBRCAm) ...

9. lynparza.com lynparza.com/ovarian-cancer/results.html

Advanced or Recurrent Ovarian Cancer - Results of ... LYNPARZA may cause serious side effects, including: Bone marrow problems called Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).