Chemotherapy +/− Bevacizumab for Ovarian and Fallopian Tube Cancer

Not currently recruiting at 291 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether different combinations of chemotherapy drugs, with or without bevacizumab (also known as Avastin), can effectively treat certain stages of ovarian or fallopian tube cancer. Chemotherapy drugs like carboplatin, paclitaxel, oxaliplatin, and capecitabine aim to stop cancer cells from growing or dividing, while bevacizumab, a monoclonal antibody, may block tumor growth. The trial compares the effectiveness of these drug combinations as first-line treatments for newly diagnosed or certain recurrent cases of these cancers. Individuals newly diagnosed with stage II-IV or with stage I recurrent epithelial ovarian or fallopian tube cancer, who have had surgery and no prior chemotherapy, might be suitable for this trial. As a Phase 3 trial, this research represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that using carboplatin, paclitaxel, and bevacizumab together is effective, but it can lead to more serious side effects. The risk of severe side effects increases by at least 2% when bevacizumab is added to the treatment for ovarian cancer.

Studies have found that the combination of oxaliplatin, capecitabine, and bevacizumab is safe and effective for treating colon cancer, especially in advanced cases.

Carboplatin and paclitaxel are usually well-tolerated and have been standard treatments for ovarian cancer for many years.

Oxaliplatin and capecitabine also have a good safety record and are commonly used for colorectal cancer.

Overall, these treatments have been thoroughly studied, and their safety varies. Participants should consider possible side effects and discuss them with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ovarian and fallopian tube cancer because they explore the potential benefits of adding bevacizumab, a targeted therapy, to chemotherapy regimens. Bevacizumab works by inhibiting the growth of blood vessels that supply the tumor, potentially making chemotherapy more effective. In one treatment arm, bevacizumab is combined with carboplatin and paclitaxel, which are standard chemotherapy drugs, with the hope of enhancing their effectiveness. Another arm tests bevacizumab with oxaliplatin and capecitabine, offering a different chemotherapy combination. This exploration of various combinations aims to improve outcomes for patients by finding the most effective mix of treatments.

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

In this trial, participants will receive different treatment combinations. One group will receive carboplatin and paclitaxel, with or without bevacizumab. Research has shown that carboplatin and paclitaxel are promising for treating ovarian cancer. Studies have found that adding bevacizumab can extend the time patients live without the cancer worsening by more than six months. Bevacizumab stops the growth of blood vessels that supply the tumor. Another group will receive oxaliplatin and capecitabine, with or without bevacizumab. Some evidence suggests this combination might be equally effective, but more research is needed to confirm this. Both treatment options aim to prevent cancer cells from growing and spreading. ^{3 4 6 7 8}

Who Is on the Research Team?

David M Gershenson

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 surgery or an open biopsy in the last 4 weeks.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6189442/

Weekly versus 3-weekly paclitaxel in combination with ... The 3-weekly regimen of carboplatin and paclitaxel is the backbone of first line adjuvant chemotherapy for advanced ovarian cancer.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1505067

Weekly vs. Every-3-Week Paclitaxel and Carboplatin for ... In conclusion, our data suggest that weekly paclitaxel did not prolong progression-free survival, as compared with paclitaxel administered every ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2778657

Efficacy and Safety of First-line Single-Agent Carboplatin ... In this randomized clinical trial of 120 vulnerable older patients with ovarian cancer, single-agent carboplatin was less feasible and active than a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01167712

Study Details | NCT01167712 | Paclitaxel and Carboplatin ... This phase III clinical trial studies two different dose schedules of paclitaxel to see how well they work in combination with carboplatin with or without ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2023/1951412

Efficacy and Safety of Paclitaxel and Carboplatin for ... Conclusion. Current evidence suggests that paclitaxel and carboplatin do not produce more satisfactory results with respect to overall survival ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8063137/

Efficacy and Safety of First-line Single-Agent Carboplatin ... This randomized clinical trial compares the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin–paclitaxel, or ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2667005424000255

Efficacy and safety of paclitaxel liposome versus ... The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy.

8. thelancet.com thelancet.com/article/S1470-2045(22)00283-2/fulltext

Weekly dose-dense chemotherapy in first-line epithelial ... The JGOG 3016 trial reported significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly (ie ...