Pre-Surgery Olaparib for Ovarian Cancer

(NEO Trial)

Recruiting at 8 trial locations

Overseen By Amit Oza, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: Platinum therapy

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Other malignancy, Brain metastases, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

71 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study that will look at the effects and how useful investigational drug olaparib is as a neoadjuvant treatment (treatment given as to shrink a tumor before the main treatment) prior to surgery in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer.

Will I have to stop taking my current medications?

The trial requires that you stop using any systemic, targeted, immunotherapy, chemotherapy, or investigational agents within 4 weeks of registration. Additionally, you cannot use potent CYP3A4 inhibitors or inducers. Please consult with the trial team about your specific medications.

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

Olaparib has shown effectiveness in treating ovarian cancer, especially in patients with BRCA mutations, by helping to shrink tumors and delay disease progression. It has been tested in various trials and is approved for use in certain types of ovarian cancer, demonstrating its potential as a personalized therapy. ^{1 2 3 4 5}

Is Olaparib safe for use in humans?

Olaparib, also known as Lynparza, has been tested in various clinical trials for ovarian cancer and has shown a generally manageable safety profile. It is approved for use in certain types of ovarian cancer, indicating it is considered safe for human use in these contexts. ^{1 2 3 5 6}

How is the drug olaparib unique for treating ovarian cancer?

Olaparib is unique because it is an oral drug specifically designed for patients with BRCA mutation-positive ovarian cancer, working by inhibiting PARP enzymes that help repair DNA damage in cancer cells. This makes it a personalized treatment option, particularly effective for those with certain genetic profiles, and it is used as maintenance therapy after chemotherapy to prolong the period without disease progression. ^{1 2 3 7 8}

Research Team

Amit Oza, MD

Principal Investigator

Princess Margaret Cancer Centre/University Health Network

Eligibility Criteria

This trial is for adults with recurrent high-grade serous ovarian, primary peritoneal or fallopian tube cancer suitable for surgery. Participants must have responded to platinum therapy after a previous recurrence and be in good health otherwise. They should not have had certain treatments recently, no history of severe allergies to similar drugs, and agree to use contraception.

Inclusion Criteria

Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation

Ability to understand and the willingness to sign a written informed consent document

My last platinum-based treatment was effective.

Exclusion Criteria

My hearing loss is not severe.

Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study

I haven't had any other cancer besides this one in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive olaparib at 300 mg twice per day for 6 weeks prior to surgery

6 weeks (+/- 2 weeks)

Surgery

Participants undergo surgery after neoadjuvant treatment

Chemotherapy

Participants receive platinum-based chemotherapy as chosen by the study doctor and per standard of care after surgery

Post-Surgery Treatment

Participants receive olaparib at 300 mg twice per day continuously after chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

2.5 years

Treatment Details

Interventions

• Olaparib

Trial Overview The study tests Olaparib as an initial treatment before surgery in patients with specific types of cancer that have recurred. It aims to see how effective this drug is at shrinking tumors when given prior to the main surgical treatment.

Participant Groups

Group I: Olaparib Prior to Surgery, Chemotherapy/Olaparib Post Surgery Experimental Treatment 2 Interventions

Olaparib, orally, at 300 mg twice per day, for 6 weeks (+/- 2 weeks) prior to surgery. Platinum-based chemotherapy chosen by the study doctor and per standard of care after surgery. Olaparib, orally, at 300 mg twice per day, continuously, after chemotherapy.

Group II: Olaparib Prior to Surgery and Post Surgery Experimental Treatment 1 Intervention

Olaparib, orally, at 300 mg twice per day, for 6 weeks (+/- 2 weeks) prior to surgery and after surgery.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

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 a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

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 (OLA) monotherapy showed a similar overall objective response rate (ORR) compared to chemotherapy (CT) in patients with relapsed ovarian cancer, with ORR of 24.3% for OLA and 28.3% for CT, indicating comparable efficacy.

In patients with platinum-resistant ovarian cancer (PROC) who had received more than four prior lines of treatment, OLA demonstrated a higher ORR of 22.9% compared to 0% for CT, suggesting that OLA may be more effective in heavily pretreated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. Vanderstichele, A., Loverix, L., Busschaert, P., 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 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 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 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]

References

1. 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]

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

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022]

5. 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]

6. France pubmed.ncbi.nlm.nih.gov

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

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

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

8. England pubmed.ncbi.nlm.nih.gov

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