Chemotherapy +/− Bevacizumab for Ovarian and Fallopian Tube Cancer

Recruiting at 283 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin

Disqualifiers: Colon cancer, CNS disease, 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: 22

Duration: 18 weeks

50 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, patients taking warfarin are excluded from participating, so you may need to discuss your specific medications with the trial team.

What evidence supports the effectiveness of the drug combination including Bevacizumab for ovarian and fallopian tube cancer?

Research shows that adding Bevacizumab to chemotherapy with carboplatin and paclitaxel can prolong the time before the cancer worsens by a few months, although it does not significantly increase overall survival. Bevacizumab is approved in the EU for treating advanced ovarian cancer, but it can cause serious side effects. ^{1 2 3 4 5}

What safety data exists for chemotherapy with bevacizumab in ovarian and fallopian tube cancer?

Bevacizumab, when used with chemotherapy for ovarian cancer, can cause side effects like high blood pressure, blood clots, bleeding, and protein in the urine. Paclitaxel, another drug used in this treatment, is generally accepted for ovarian cancer but still has ongoing studies to better understand its safety and effectiveness. ^{1 6 7 8 9}

How does the drug combination of chemotherapy and bevacizumab differ from other treatments for ovarian and fallopian tube cancer?

This treatment is unique because it combines bevacizumab, a drug that blocks blood vessel growth in tumors, with chemotherapy drugs like carboplatin and paclitaxel, which are standard for ovarian cancer. Bevacizumab has been shown to extend the time before the cancer progresses when added to chemotherapy, although it may not significantly increase overall survival and can have serious side effects. ^{1 3 4 10 11}

What is the purpose of this trial?

This randomized phase III trial studies carboplatin given together with paclitaxel with or without bevacizumab to see how well it works compared with oxaliplatin given together with capecitabine with or without bevacizumab as first-line therapy in treating patients with newly diagnosed stage II-IV, or recurrent (has come back) stage I epithelial ovarian or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. It is not yet known which regimen of combination chemotherapy given together with or without bevacizumab is more effective in treating epithelial ovarian cancer or fallopian tube cancer.

Research Team

David M Gershenson

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with newly diagnosed stage II-IV or recurrent stage I epithelial ovarian or fallopian tube cancer who've had surgery and are within certain health parameters (like normal organ function tests). They must not have received prior treatment for gynecologic or colorectal cancer, have no severe allergies to specific antibodies, no recent history of significant cardiovascular events, and agree to effective birth control if applicable.

Inclusion Criteria

Your urine test should show low levels of protein, and if it shows higher levels, another test will be done to make sure it's not too high.

You are expected to live for more than 3 months.

I had surgery for ovarian or fallopian tube cancer, including an appendectomy.

Exclusion Criteria

I have not had any cancer other than non-melanoma skin cancer in the past 5 years.

I have not had surgery or an open biopsy in the last 4 weeks.

I had minor surgery or biopsy over a week ago and my wound is healing well.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive chemotherapy with carboplatin and paclitaxel or oxaliplatin and capecitabine, with or without bevacizumab, every 3 weeks for 6 courses

18 weeks

6 visits (in-person)

Bevacizumab Extension

Patients receiving bevacizumab continue treatment every 3 weeks for 12 additional courses

36 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 4-6 weeks, every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Bevacizumab
• Capecitabine
• Carboplatin
• Oxaliplatin
• Paclitaxel

Trial Overview The study compares two chemotherapy regimens: Carboplatin with Paclitaxel versus Oxaliplatin with Capecitabine. Both may be given with Bevacizumab, a monoclonal antibody. The goal is to determine which combination is more effective as first-line therapy in treating these cancers.

Participant Groups

Group I: Arm IV (oxaliplatin, capecitabine, bevacizumab) Experimental Treatment 5 Interventions

Patients receive oxaliplatin and capecitabine as in arm II, and bevacizumab as in arm III.

Group II: Arm III (carboplatin, paclitaxel, bevacizumab) Experimental Treatment 5 Interventions

Patients receive carboplatin and paclitaxel IV as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes alone on day 1. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

Group III: Arm II (oxaliplatin and capecitabine) Experimental Treatment 4 Interventions

Patients receive oxaliplatin IV over 2-6 hours on day 1 and capecitabine PO BID on days 1-14. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Group IV: Arm I (carboplatin and paclitaxel) Experimental Treatment 4 Interventions

Patients receive carboplatin IV over 30-60 minutes on day 1 and paclitaxel IV over 3 hours on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

The combination of docetaxel, oxaliplatin, and bevacizumab as a first-line treatment for advanced ovarian, peritoneal, or fallopian tube cancer showed a promising 12-month progression-free survival rate of 65.7% among 132 patients, with a median progression-free survival of 16.3 months.

The treatment was generally safe, with the most common severe side effects being neutropenia and leukopenia, and only one reported fatal gastrointestinal perforation, indicating no unexpected safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. Herzog, TJ., Monk, BJ., Rose, PG., et al.[2021]

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]

In a study of 114 patients with advanced ovarian cancer treated with carboplatin, paclitaxel, and bevacizumab, 41% experienced arthralgia (joint pain), indicating it is a common side effect of this treatment.

Although patients with arthralgia had a median progression-free survival of 29 months compared to 18 months for those without, this difference was not statistically significant when accounting for other factors, suggesting that while arthralgia is prevalent, it may not directly impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy. Ventriglia, J., Paciolla, I., Pisano, C., et al.[2021]

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]

In a study of 299 patients with advanced ovarian cancer, combining bevacizumab with carboplatin/paclitaxel resulted in a median progression-free survival of 15.4 months, indicating its efficacy as a front-line treatment.

The treatment was generally safe, with 54% of patients experiencing grade 3/4 adverse events, primarily hypertension and neutropenia, and a 1-year overall survival rate of 94%, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. Hall, M., Bertelli, G., Li, L., et al.[2020]

In a phase III trial involving 484 patients with platinum-sensitive recurrent ovarian cancer, the combination of bevacizumab (BV) with gemcitabine and carboplatin (GC) significantly improved progression-free survival (PFS) compared to GC alone, with a median PFS of 12.4 months versus 8.4 months.

The addition of BV also led to a higher objective response rate (78.5% vs. 57.4%) and longer duration of response (10.4 months vs. 7.4 months), although it was associated with increased rates of grade 3 or higher hypertension and proteinuria, indicating a need for monitoring these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. Aghajanian, C., Blank, SV., Goff, BA., et al.[2022]

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]

References

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

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. [2021]

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

Treatment of ovarian cancer: current status. [2015]

3. France pubmed.ncbi.nlm.nih.gov

Bevacizumab and advanced-stage ovarian cancer. Yet another oncological indication, but still best to avoid using this drug. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer patients. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Front-line therapy of advanced epithelial ovarian cancer: standard treatment. [2022]

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

Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy. [2021]

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

USA update on paclitaxel in ovarian cancer. [2019]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Bevacizumab toxicity in heavily pretreated recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. [2020]

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

OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. [2022]

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]