Combination Therapy for Ovarian Cancer

(DUO-O Trial)

Recruiting at 186 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

1407 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination therapy for ovarian cancer?

Research shows that combining bevacizumab with paclitaxel and carboplatin can improve outcomes for ovarian cancer patients, especially those with platinum-resistant cancer. Bevacizumab, when added to chemotherapy, has been effective in prolonging survival and improving quality of life in various settings of ovarian cancer treatment. ^{1 2 3 4 5}

Is the combination therapy for ovarian cancer safe for humans?

The combination therapy involving drugs like bevacizumab, paclitaxel, and carboplatin has been studied for safety in ovarian cancer patients. While these treatments can be effective, they may cause side effects such as gastrointestinal issues and other grade 3-4 toxicities, which are serious but manageable with medical supervision. ^{1 6 7 8 9}

What makes the combination therapy of Bevacizumab, Carboplatin, Durvalumab, and Paclitaxel unique for ovarian cancer?

This combination therapy is unique because it includes Bevacizumab, an anti-angiogenic drug that inhibits blood vessel growth in tumors, combined with standard chemotherapy drugs Carboplatin and Paclitaxel, and adds Durvalumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This approach aims to enhance the effectiveness of treatment by targeting both the tumor's blood supply and the immune system. ^{1 4 10 11 12}

What is the purpose of this trial?

This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.

Research Team

Philipp Harter

Principal Investigator

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Carol Aghajanian

Principal Investigator

GOG

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients. [2023]

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

Pharmaceutical Management of Ovarian Cancer: Current Status. [2020]

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

Treatment of ovarian cancer: current status. [2015]

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

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma. [2020]

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

Evaluation of the antitumor activity of NOV202, a novel microtubule targeting and vascular disrupting agent. [2018]

6. England pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Bevacizumab plus microtubule targeting agents in heavily pre-treated ovarian cancer patients: a retrospective study. [2019]

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

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. [2022]

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

Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis. [2021]

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

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

12. England pubmed.ncbi.nlm.nih.gov

Optimal first-line treatment in ovarian cancer. [2022]