Combination Therapy for Ovarian Cancer

(DUO-O Trial)

Not currently recruiting at 221 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: PARP inhibitors, Immune therapy

Disqualifiers: Autoimmune disorders, Cardiovascular disease, Brain metastases, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 4 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for advanced ovarian cancer. Researchers aim to evaluate how well adding durvalumab, which helps the immune system fight cancer, works with standard chemotherapy and bevacizumab (also known as Avastin), which prevents tumors from growing new blood vessels. Participants will receive different combinations of these drugs to identify the most effective treatment. Women recently diagnosed with advanced ovarian cancer and planning surgery may qualify to join. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it excludes those who have had prior systemic anti-cancer therapy for ovarian cancer or treatment with certain drugs, so it's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of durvalumab, bevacizumab, and olaparib has been tested for safety in ovarian cancer patients. One study found that this combination was generally well-tolerated, with tiredness and nausea as the most common side effects, which most patients managed. Serious side effects occurred less frequently.

Another study examined durvalumab and bevacizumab with chemotherapy and found this combination was also well-tolerated. Patients experienced typical side effects like nausea and low blood cell counts, similar to those usually seen with chemotherapy.

Overall, the studies suggest these treatments are safe for patients. However, as with any treatment, risks exist, and side effects can vary from person to person. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ovarian cancer because they combine several powerful drugs to potentially enhance efficacy. Unlike traditional options that may use single-agent chemotherapy, this approach integrates bevacizumab, a drug that inhibits blood vessel growth in tumors, with durvalumab, an immune checkpoint inhibitor that helps unleash the body's immune system against cancer cells. Additionally, the potential addition of olaparib, a PARP inhibitor, could offer further benefits by targeting cancer cells' DNA repair mechanisms. This multi-pronged strategy aims to improve outcomes by attacking the cancer in several different ways, which could be more effective than existing treatments.

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

Studies have shown that bevacizumab can help ovarian cancer patients live longer without disease progression, with some experiencing over six months of added benefit. In this trial, one group will receive platinum-based chemotherapy with bevacizumab and a durvalumab placebo, followed by maintenance bevacizumab and placebo treatments. Another group will receive the same chemotherapy with both bevacizumab and durvalumab, followed by maintenance bevacizumab and durvalumab. Research suggests that adding durvalumab can improve outcomes for those with recurring ovarian cancer. Additionally, some participants will receive bevacizumab, durvalumab, and olaparib, a combination that has shown promise in treating advanced ovarian cancer. These findings suggest that the combination therapy under study could effectively manage newly diagnosed advanced ovarian cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Philipp Harter

Principal Investigator

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Carol Aghajanian

Principal Investigator

GOG

Are You a Good Fit for This Trial?

This trial is for women over 18 with newly diagnosed advanced ovarian cancer, including certain subtypes and related cancers. They should be fit for surgery, have a performance status of 0-1 indicating they are fully active or restricted in physically strenuous activity but ambulatory, and not pregnant. Exclusions include autoimmune disorders, brain metastases, recent malignancies except specific treated cases, ongoing severe side effects from past treatments, cardiovascular disease, prior treatment for ovarian cancer or allergies to the study drugs.

Inclusion Criteria

I am postmenopausal or not currently pregnant.

My organs and bone marrow are functioning well.

My tumor has been tested for BRCA1/2 mutations.

Exclusion Criteria

My ovarian cancer is not the common type, it's either borderline, low grade, or mucinous.

I have or had an autoimmune or inflammatory disorder.

My BRCA mutation status is unknown.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive platinum-based chemotherapy in combination with bevacizumab and durvalumab, followed by maintenance therapy with bevacizumab, durvalumab, and olaparib

Approximately 4 years

Follow-up

Participants are monitored for safety, efficacy, and quality of life after treatment

Approximately 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Durvalumab
• Olaparib
• Paclitaxel

Trial Overview The study tests Durvalumab combined with chemotherapy (Carboplatin+Paclitaxel) and Bevacizumab versus placebo controls followed by maintenance therapy with Durvalumab and Bevacizumab alone or alongside Olaparib. It's a Phase III trial where patients are randomly assigned to different treatment groups without knowing which one they're receiving.

How Is the Trial Designed?

Group I: tBRCAm cohort Experimental Treatment 4 Interventions

Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib. Bevacizumab is optional according to local practice.

Group II: Arm 3 Experimental Treatment 4 Interventions

Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.

Group III: Arm 2 Experimental Treatment 4 Interventions

Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.

Group IV: Arm 1 Active Control 4 Interventions

Platinum-based chemotherapy in combination with bevacizumab and durvalumab placebo (saline IV infusion) followed by maintenance bevacizumab, durvalumab placebo (saline IV infusion) and olaparib placebo (tablets).

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

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

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

GOG Foundation, Inc. (GOG Foundation)

Collaborator

Trials

1

Recruited

1,400+

Myriad Genetic Laboratories, Inc.

Industry Sponsor

Trials

32

Recruited

14,600+

Published Research Related to This Trial

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]

Combining Bevacizumab (Bev) with standard chemotherapy significantly improves progression-free survival (PFS) and overall survival (OS) in newly diagnosed ovarian cancer patients, with a notable effect size (HR for OS of 0.87) based on data from 2 trials involving 2776 patients.

While both doses of Bev (7.5 mg/kg and 15 mg/kg) showed similar efficacy in PFS and OS, the higher dose was associated with increased toxicities, suggesting that the lower dose may be the safer and more optimal choice for patients at high risk for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis. Zhou, M., Yu, P., Qu, X., et al.[2021]

Bevacizumab, when combined with carboplatin and paclitaxel, significantly prolongs progression-free survival in women with newly diagnosed advanced ovarian cancer, as shown in the GOG-0218 and ICON7 studies.

In patients with recurrent platinum-sensitive ovarian cancer, bevacizumab combined with carboplatin and gemcitabine also extends progression-free survival, demonstrating its efficacy in both first-line and second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Dhillon, S.[2019]

In a study of 90 ovarian cancer patients, the combination of bevacizumab with paclitaxel and carboplatin significantly improved treatment outcomes, with higher remission and disease control rates compared to those receiving only paclitaxel and carboplatin.

The combined treatment also led to lower levels of tumor markers CA199, CEA, and CA242 without increasing the risk of adverse effects, indicating it is a safe and effective option for improving patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients. Jiang, Q., Qian, H., Mei, L., et al.[2023]

Paclitaxel has recently become a standard chemotherapy treatment for advanced ovarian cancer, especially when combined with platinum compounds, based on a large randomized trial by the Gynaecologic Oncology Group.

Ongoing clinical trials are investigating the optimal use of paclitaxel, including its dosage, administration schedule, and comparing the effectiveness and side effects of different platinum combinations (carboplatin vs. cisplatin).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. Ozols, RF.[2019]

Bevacizumab (Avastin) has been approved for use in combination with other therapies for patients with platinum-resistant ovarian cancer, showing antitumor activity in this challenging setting.

Despite the overall low response rates (around 10%) to treatments for platinum-resistant ovarian cancer, bevacizumab is currently the most studied antiangiogenic therapy, with ongoing research into alternative treatments like tyrosine kinase inhibitors and angiopoietin inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. McClung, EC., Wenham, RM.[2022]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04015739

Tri Association in Patient With Advanced Epithelial Ovarian ... Assessing the safety and efficacy of the bevacizumab, Olaparib and Durvalumab (MEDI 4736) combination in patient with high grade serous or high grade ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7418587/

A multicenter phase II randomized trial of durvalumab ... Patients with recurrent ovarian clear cell carcinoma treated with durvalumab will have improved progression-free survival compared with those ...

3. avastin.com avastin.com/hcp/ovar/efficacy-data.html

Avastin® (bevacizumab) Clinical Trials for Ovarian Cancer Ovarian Cancer: Avastin Efficacy Data · Patients achieved a median PFS benefit of >6 months in stage III or IV ovarian cancer after primary surgery · Select ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825822015426

Phase Ib study of AVB-S6-500 (axl inhibition) in ... The combination of AVB-S6-500 and durvalumab was tolerable in this PROC patient population at all dosing levels tested.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12372840/

Bevacizumab Efficacy and Tolerability in Patients with ... Conclusion. Many studies have shown the effectiveness and survival benefit of bevacizumab in epithelial ovarian cancer. In contrast, the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10914754/

Bevacizumab, olaparib, and durvalumab in patients with ... Bevacizumab, olaparib, and durvalumab in patients with relapsed ovarian cancer: a phase II clinical trial from the GINECO group

7. astrazeneca.com astrazeneca.com/media-centre/press-releases/2023/lynparza-and-imfinzi-combination-reduced-risk-of-disease-progression-or-death-vs-chemotherapy-and-bevacizumab-in-patients-with-advanced-ovarian-cancer-without-tumour-brca-mutations-in-the-duo-o-phase-iii-trial.html

Lynparza and Imfinzi combination reduced risk of disease ... The combination of Lynparza, Imfinzi, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 37% versus chemotherapy and ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02331-7/fulltext

751P Safety and tolerability of durvalumab (D) ... Safety and tolerability of durvalumab (D) + carboplatin/paclitaxel (CP) + bevacizumab (B) followed by D, B + olaparib (O) maintenance (mtx) in patients (pts)

9. onclive.com onclive.com/view/chemotherapy-plus-durvalumab-bevacizumab-and-olaparib-fails-to-offer-os-benefit-in-newly-diagnosed-non-tbrca-mutated-ovarian-cancer

Chemotherapy Plus Durvalumab, Bevacizumab, and ... Chemotherapy plus durvalumab, bevacizumab, and olaparib did not significantly prolong OS in non-tBRCA-mutated ovarian cancer.

10. targetedonc.com targetedonc.com/view/durvalumab-combo-maintains-pfs-benefit-in-ovarian-cancer

Durvalumab Combo Maintains PFS Benefit in Ovarian ... The combination of durvalumab, chemotherapy, and bevacizumab, followed by maintenance with olaparib, durvalumab, and bevacizumab, improved progression-free ...