Pre-Surgery Olaparib for Ovarian Cancer

(NEO Trial)

Not currently recruiting at 10 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the drug olaparib in shrinking tumors in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer before surgery. Patients will take olaparib (also known as Lynparza) orally for about six weeks before surgery. Some patients will continue taking it after surgery, either alone or with chemotherapy. This trial suits those who have had high-grade ovarian or related cancers, responded well to previous platinum-based treatments, and have been cancer-free for at least six months. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, offering them a chance to contribute to significant advancements in cancer treatment.

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.

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

Research has shown that olaparib has been tested in several studies to assess its safety and efficacy. In past studies, patients generally tolerated olaparib well. Common side effects included fatigue, nausea, and a drop in blood cells, which can lead to anemia (a condition characterized by insufficient healthy red blood cells). Most patients found these side effects manageable.

The SOLO-1 trial focused on using olaparib for ovarian cancer, and the safety results aligned with those from other studies, revealing no major surprises or new safety concerns. Olaparib is already FDA-approved for treating certain types of cancer, indicating it has passed strict safety evaluations for those uses. However, individual experiences may vary, and participating in a trial involves close monitoring by doctors who carefully observe how the treatment affects participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for ovarian cancer, which typically involve surgery followed by chemotherapy, Olaparib offers a targeted approach by inhibiting the enzyme PARP (poly ADP-ribose polymerase). This mechanism helps prevent cancer cells from repairing their DNA, potentially leading to more effective cancer cell death. Researchers are excited about Olaparib because it can be used both before and after surgery, which might enhance its effectiveness by shrinking tumors pre-surgery and reducing recurrence risk post-surgery. Additionally, Olaparib is taken orally, which can be more convenient compared to traditional intravenous chemotherapy.

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

Research has shown that olaparib, a drug that blocks certain cancer cell functions, holds promise for treating ovarian cancer. In this trial, participants will receive olaparib either before surgery and continue after surgery, or before surgery followed by chemotherapy and then olaparib post-surgery. One study found that 92% of patients taking olaparib were cancer-free after one year, compared to 66% who took a placebo (a pill with no active drug). Another study revealed that 168 out of 255 patients taking olaparib with another drug did not experience cancer growth or recurrence, while only 40 out of 132 patients taking a placebo had the same result. These findings suggest that olaparib can help prevent cancer from worsening, offering hope for those with ovarian cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Amit Oza, MD

Principal Investigator

Princess Margaret Cancer Centre/University Health Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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, 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 (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]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8190876/

Subgroup Analysis Findings From the SOLO1 Trial - PMC Of those receiving olaparib, 92%, 81%, and 71% were progression free at 1, 2, and 3 years (v 66%, 45%, and 35% who received placebo), respectively. Additional ...

3. 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 ...

4. 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%.

5. lynparzahcp.com lynparzahcp.com/ovarian-cancer/efficacy/paola-1.html

PAOLA-1 Phase 3 Trial - LYNPARZA® (olaparib) PARP Inhibitor In PAOLA-1, of patients with newly diagnosed advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in patients who ...

6. lynparzahcp.com lynparzahcp.com/ovarian-cancer/safety-tolerability/solo-1.html

Safety & Tolerability in the SOLO-1 Trial Learn about the safety profile and tolerability of LYNPARZA® (olaparib) as well as the potential adverse reactions found in the SOLO-1 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4992984/

Efficacy and safety of olaparib monotherapy in germline ... With olaparib monotherapy, objective tumor response rates in Study 42 were 26% for all patients with gBRCA1/2m cancers, and 31% for patients with gBRCA1/2m ...

8. lynparza.com lynparza.com/

LYNPARZA® (olaparib) - Official Patient Website Find out about LYNPARZA® (olaparib), a targeted treatment for certain types of cancer. See important safety information, downloadable resources and more.

9. accc-cancer.org accc-cancer.org/docs/ossn-network/industry-news-announcements/solo3-dhcp.pdf?sfvrsn=b70b4ab8_2

solo3-dhcp.pdf Safety data, other than OS, reported for Lynparza in the SOLO3 study were consistent with those reported in other clinical trials with Lynparza. This letter is ...

10. lynparzahcp.com lynparzahcp.com/ovarian-cancer/resource-library.html

LYNPARZA Resource Library for Ovarian Cancer | For HCPs Access LYNPARZA® (olaparib) resource library for ovarian cancer, including clinical guides, patient materials, and prescribing information for HCPs.