Biomarker-Driven Therapy for Ovarian Cancer

(BOUQUET Trial)

Not currently recruiting at 98 trial locations

Overseen By Reference Study ID Number: WO42178 https://forpatients.roche.com/

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Chemotherapy, Radiotherapy, Immunotherapy, others

Disqualifiers: Pregnancy, CNS metastases, Severe infection, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests various treatments for individuals with persistent or recurring rare ovarian, fallopian tube, or peritoneal cancer. Researchers aim to assess the safety and effectiveness of these treatments for different genetic profiles by using specific drugs matched to genetic markers in the tumors. Individuals who have tried 1 to 4 other treatments, including at least one platinum-based therapy, and whose cancer returned within 6 months after the last platinum treatment, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy, radiotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, or investigational therapy at least 28 days before starting the study treatment. Hormonal therapy must be stopped at least 14 days before starting the study treatment.

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

Previous studies found Inavolisib safe for long-term use, with no new safety concerns. Giredestrant also proved safe when combined with a CDK4/6 inhibitor like Abemaciclib.

Research has shown that the combination of Atezolizumab, Bevacizumab, and Cyclophosphamide is safe, with common side effects like tiredness and diarrhea, which are usually manageable.

Studies on Ipatasertib and Paclitaxel suggest this combination is safe and may help shrink tumors.

Cobimetinib, tested with other treatments, was generally safe, even at higher doses.

Trastuzumab Emtansine, evaluated in many patients, is considered safe for treating certain types of breast cancer. It has a well-known safety profile and is generally well-tolerated.

Adding Atezolizumab to Bevacizumab did not interfere with other treatments, and the common side effects were as expected.

Since this trial is in Phase 2, these treatments have demonstrated enough safety in earlier studies to progress to this stage. This phase helps confirm safety and determine the best dose for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer targeted approaches for ovarian cancer based on specific genetic alterations. For example, Inavolisib combined with Palbociclib and Letrozole targets tumors with PIK3CA alterations, potentially improving outcomes by focusing on the genetic drivers of cancer growth. Cobimetinib, on the other hand, targets tumors with BRAF, NRAS, KRAS, or NF1 alterations, which could offer a new way to tackle these specific genetic changes. Additionally, Giredestrant and Abemaciclib target estrogen receptor-positive tumors, providing a novel approach for managing hormone-driven cancers. These treatments differ from standard chemotherapy by honing in on the molecular makeup of the cancer, which may lead to more effective and personalized treatment options.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown promising results for the treatments tested in this trial. Participants in the Inavolisib and Giredestrant arm demonstrated long-term safety and tolerability, crucial for ongoing cancer treatment. In the Atezolizumab, Bevacizumab, and Cyclophosphamide arm, lasting responses were observed, although adding Atezolizumab did not significantly improve outcomes in some cases. The combination of Ipatasertib and Paclitaxel, tested in another arm, may increase tumor response and improve survival rates, indicating potential effectiveness. Cobimetinib, studied in a separate arm, showed encouraging results in certain genetic types of ovarian cancer, with a significant rate of disease control. Trastuzumab Emtansine, tested in its own arm, demonstrated promising effectiveness in patients with HER2-amplified tumors, suggesting it could work against certain ovarian cancers. Overall, these investigational treatments in the various arms of this trial offer hope for better outcomes by targeting specific cancer types. ^{5 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for patients with rare epithelial ovarian tumors that have come back or didn't go away after treatment. They must have had 1-4 previous treatments including platinum-based therapy, be in good physical condition, and agree to use birth control. It's not for those who are pregnant, breastfeeding, or have certain other cancers or severe infections.

Inclusion Criteria

You have a disease that can be measured using a specific set of guidelines.

Agreement to remain abstinent or use contraception, and refrain from donating eggs for women of childbearing potential

My blood and organs are functioning well.

Exclusion Criteria

I have been diagnosed with endometrial cancer at the same time as another primary cancer.

My current diagnosis is a borderline ovarian tumor.

I have a specific type of advanced ovarian, fallopian tube, or peritoneal cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preliminary Phase

Participants receive biomarker-selected treatments to evaluate efficacy and safety

Until unacceptable toxicity or disease progression

Expansion Phase

Potential expansion of treatment based on preliminary phase results

Until unacceptable toxicity or disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Atezolizumab
• Bevacizumab
• Cobimetinib
• Cyclophosphamide
• Giredestrant
• Inavolisib
• Ipatasertib
• Letrozole
• Luteinizing Hormone-Releasing Hormone (LHRH) Agonists
• Olaparib
• Paclitaxel
• Palbociclib
• Trastuzumab Emtansine

Trial Overview

The study tests how well different drugs work based on tumor markers in patients with persistent/recurrent ovarian tumors. Drugs like Abemaciclib and Trastuzumab Emtansine among others will be used. The trial includes initial and potential expansion phases to assess safety and effectiveness.

How Is the Trial Designed?

Group I: Trastuzumab Emtansine (ERBB2-amplified/mutant tumors) Experimental Treatment 1 Intervention

Participants in the Trastuzumab Emtansine arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group II: Ipatasertib + Paclitaxel (PIK3CA/AKT1/PTEN-altered tumors) Experimental Treatment 2 Interventions

Participants in the Ipatasertib + Paclitaxel arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group III: Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors) Experimental Treatment 4 Interventions

Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group IV: Inavolisib + Palbociclib (PIK3CA-altered tumors) Experimental Treatment 2 Interventions

Participants in the Inavolisib + Palbociclib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group V: Inavolisib + Olaparib (Non-matched) Experimental Treatment 2 Interventions

Participants in the Inavolisib + Olaparib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group VI: Inavolisib + Giredestrant (ER+ and PIK3CA-altered tumors) Experimental Treatment 2 Interventions

Participants in the Inavolisib + Giredestrant arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group VII: Inavolisib + Bevacizumab (PIK3CA-altered tumors) Experimental Treatment 2 Interventions

Participants in the Inavolisib + Bevacizumab arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group VIII: Giredestrant + Abemaciclib (ER+ tumors) Experimental Treatment 3 Interventions

Participants in the Giredestrant + Abemaciclib arm will receive treatment until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Group IX: Cobimetinib (BRAF/NRAS/KRAS/NF1-altered tumors) Experimental Treatment 1 Intervention

Participants in the Cobimetinib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group X: Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched) Experimental Treatment 3 Interventions

Participants in the Atezolizumab + Bevacizumab + Cyclophosphamide arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.

Group XI: Atezolizumab + Bevacizumab (Non-matched) Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Bevacizumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Published Research Related to This Trial

Epithelial ovarian cancer (EOC) has a high initial response rate to platinum-based treatments (70-80%), but long-term survival remains low due to chemoresistance and the disease's heterogeneity, which includes multiple histological subtypes.

Recent advancements in biomarker research, such as identifying BRCA and KRAS mutations, have led to the development of targeted therapies like PARP inhibitors and immunotherapy, which may improve treatment outcomes for patients with EOC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the Clinical Impact of Predictive Biomarkers in Serous Ovarian Carcinomas. Le Page, C., Chung, J., Rahimi, K., et al.[2021]

The PENELOPE trial found that adding pertuzumab to chemotherapy for patients with platinum-resistant ovarian cancer did not significantly improve overall survival, with a hazard ratio of 0.90, indicating no meaningful difference between the treatment and control groups.

While pertuzumab did not enhance patient-reported outcomes overall, it was associated with increased diarrhea symptoms, suggesting a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Lorusso, D., Hilpert, F., González Martin, A., et al.[2022]

The combination of aflibercept and docetaxel was found to be safe and well-tolerated in women with recurrent ovarian cancer, with no dose-limiting toxicities reported during the phase 1 study.

In the phase 2 trial involving 46 patients, the treatment achieved a confirmed objective response rate of 54%, indicating significant antitumor activity, which supports further clinical development of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1-2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Coleman, RL., Duska, LR., Ramirez, PT., et al.[2021]

Adjuvant hormone therapy (AHT) significantly improves overall survival in women with epithelial ovarian cancer, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death compared to those not receiving AHT.

The study, which included 150 patients followed for a median of 19.1 years, also showed that AHT enhances relapse-free survival, suggesting that it not only helps manage menopausal symptoms but may also positively impact cancer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial. Eeles, RA., Morden, JP., Gore, M., et al.[2019]

Despite high initial response rates to surgery and platinum-based chemotherapy in ovarian cancer, most patients experience relapse, highlighting the need for new treatment strategies to improve survival.

Recent phase III trials have shown that the anti-angiogenic agent bevacizumab, when used alongside chemotherapy and as maintenance therapy, can positively impact outcomes in first-line ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal first-line treatment in ovarian cancer. Raja, FA., Chopra, N., Ledermann, JA.[2022]

In a phase II study of 42 ER-positive ovarian cancer patients treated with letrozole, 17% showed a significant response in CA125 levels, indicating some efficacy of the drug in this specific patient group.

The study identified predictive markers, such as low HER2 expression, that may help determine which patients are more likely to respond to letrozole treatment, highlighting the potential for personalized therapy in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. Smyth, JF., Gourley, C., Walker, G., et al.[2022]

The standard treatment for platinum-resistant ovarian cancer involves non-platinum chemotherapy, with weekly paclitaxel showing the greatest benefits, but overall response rates remain modest, highlighting the need for improved therapies.

Recent trials indicate that while combination treatments with antiangiogenics have improved outcomes, there is still a lack of reliable biomarkers to predict treatment response, emphasizing the importance of thoughtful clinical trial designs and the exploration of novel therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. Eskander, RN., Moore, KN., Monk, BJ., et al.[2023]

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

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