Continued Olaparib for Cancer

(ROSY-O Trial)

Enrolling by invitation at 125 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Olaparib

Disqualifiers: Grade 3 toxicity, other research, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Duration: Indefinite

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the continued use of a cancer treatment called olaparib. The researchers aim to determine if patients who have benefited from this treatment in other studies can maintain positive effects. It targets individuals who participated in a previous cancer study with olaparib and continue to experience good results. Participants should not have severe side effects from the treatment and must avoid conflicting medications. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of this treatment for wider use.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any prohibited medications while participating.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that olaparib is usually well-tolerated by patients. However, some serious side effects can occur. For example, one study found that 31% of patients experienced serious side effects, including high blood pressure, when olaparib was combined with another drug.

Another study found that olaparib could sometimes cause bone marrow problems, such as Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML). Despite this, olaparib is generally safe for many patients when used alone. It has been used as a maintenance treatment for relapsed ovarian cancer and is usually well-tolerated.

In summary, while olaparib carries risks, many patients handle it well, especially when used alone. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cancer?

Olaparib is unique because it specifically targets cancer cells with DNA repair defects, notably those with BRCA mutations. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, olaparib selectively inhibits the enzyme PARP, crucial for repairing DNA in these cancer cells, leading to their death while sparing healthy cells. Researchers are excited about olaparib because it offers a more targeted approach, potentially resulting in fewer side effects and better outcomes for patients with certain genetic profiles.

What is the effectiveness track record for Olaparib in cancer treatment?

Research has shown that olaparib, the treatment under study in this trial, can help delay ovarian cancer growth. In previous studies, patients taking olaparib lived longer without their cancer worsening compared to those on a placebo. For example, one study found that 168 out of 255 patients taking olaparib with bevacizumab did not experience cancer growth or recurrence, while only 40 out of 132 patients taking bevacizumab with a placebo had the same outcome. Additionally, olaparib reduced the risk of breast cancer recurrence, development of a second cancer, or death by 35%. These findings suggest that olaparib can effectively control cancer in some patients. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for patients who have previously been in an oncology study with Olaparib and are still benefiting from it. They must have signed consent, not be on prohibited meds, not have unresolved high-grade toxicity or disease progression, and can't get the drug commercially for free.

Inclusion Criteria

I am benefiting from ongoing olaparib treatment from a previous AZ cancer study.

I am benefiting from an ongoing AstraZeneca study treatment.

Provision of signed and dated, written ICF.

Exclusion Criteria

Concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.

I was removed from the main study because of side effects or my disease got worse.

I am not taking any medications that are not allowed in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue to receive olaparib treatment as they derive clinical benefit

Indefinite

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term follow-up

Participants are monitored for safety outcomes up to approximately 10 years

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The ROSY-O study aims to continue providing Olaparib to patients who were part of a previous study and are still seeing positive effects. The focus is on those with ovarian or breast cancer who've shown clinical benefits as determined by their doctor.

How Is the Trial Designed?

Group I: Olaparib Experimental Treatment 1 Intervention

Treatment

Who Is Running the Clinical Trial?

AstraZeneca

Lead 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

Published Research Related to This Trial

Olaparib is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[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, 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 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 (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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9870219/

Overall Survival With Maintenance Olaparib at a 7-Year ... Results indicate a clinically meaningful, albeit not statistically significant, improvement in OS with maintenance olaparib versus placebo, with two thirds of ...

2. lynparzahcp.com lynparzahcp.com/ovarian-cancer/efficacy/solo-1.html

LYNPARZA SOLO-1 Trial: Efficacy in Ovarian Cancer | For HCPs Primary analysis. Unprecedented efficacy: Median PFS was not reached with LYNPARZA vs ~1.2 years (13.8 months) with placebo1,5.

3. 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%.

4. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html

LYNPARZA® (olaparib) demonstrated clinically meaningful ... LYNPARZA reduced the risk of invasive breast cancer recurrence, second cancers or death by 35% (HR 0.65; 95% CI; 0.53-0.78) and reduced the risk ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10948524/

Clinical effectiveness and safety of olaparib in BRCA-mutated ... Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based ...

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

Adverse Reactions and Tolerability for LYNPARZA® (olaparib ... Serious adverse reactions occurred in 31% of patients who received LYNPARZA + bevacizumab. Serious adverse reactions in >5% of patients included hypertension ( ...

7. lynparza.com lynparza.com/side-effects.html

Side Effects of LYNPARZA® (olaparib) LYNPARZA may cause serious side effects, including: Bone marrow problems called Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).

8. 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 ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26051946/

Safety evaluation of olaparib for treating ovarian cancer Oral olaparib 400 mg twice daily has acceptable tolerability when administered as maintenance monochemotherapy in women with relapsed OC.

10. nejm.org nejm.org/doi/full/10.1056/NEJMoa1911440

Olaparib for Metastatic Castration-Resistant Prostate Cancer The median overall survival at interim analysis (data maturity, 41%) was 17.5 months in the olaparib group and 14.3 months in the control group (hazard ratio ...