Chemotherapy + Bevacizumab for Ovarian & Related Cancers

Not currently recruiting at 653 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Targeted therapy, Hormonal therapy

Disqualifiers: Prior radiotherapy, Cardiovascular disease, Active infection, 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

Compensation: Varies

Number of Visits: 9

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two chemotherapy drugs, paclitaxel and carboplatin, with or without bevacizumab (also known as Avastin), in treating advanced ovarian, primary peritoneal, or fallopian tube cancers. Paclitaxel and carboplatin aim to stop cancer cell growth, while bevacizumab helps prevent tumors from obtaining the blood supply they need. The trial compares two schedules for administering paclitaxel to determine which is more effective. Ideal participants are those diagnosed with stage II-IV ovarian, primary peritoneal, or fallopian tube cancer with measurable disease. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain blood thinners like warfarin, you may need to maintain a specific dose. It's best to discuss your current 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 paclitaxel and carboplatin is generally well-tolerated by patients with ovarian cancer. This drug combination is a common and standard treatment for this type of cancer. One study found no significant difference in safety whether administered weekly or every three weeks. Another study confirmed the effectiveness of using paclitaxel and carboplatin together without causing unexpected side effects.

Patients in earlier trials demonstrated that this chemotherapy combination is manageable. However, like any cancer treatment, some side effects such as nausea or tiredness can occur, but healthcare providers usually expect and monitor these. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of chemotherapy with Bevacizumab for ovarian and related cancers because it adds a unique approach to tackling these conditions. Bevacizumab is an antibody that targets and inhibits a protein called VEGF, which is responsible for the growth of blood vessels that feed tumors. This mechanism of action is different from traditional chemotherapy, which directly kills cancer cells. By combining Bevacizumab with standard chemotherapy drugs like Carboplatin and Paclitaxel, there's potential for a more effective treatment that not only attacks cancer cells but also cuts off their nutrient supply, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for ovarian and related cancers?

Research has shown that using paclitaxel and carboplatin together is a common and effective treatment for ovarian cancer. This combination helps stop cancer cells from growing and spreading. In this trial, participants in Arm I will receive paclitaxel and carboplatin every three weeks, while those in Arm II will receive paclitaxel weekly and carboplatin every three weeks. One study found that changing the schedule of paclitaxel from every three weeks to weekly did not significantly affect how long patients lived without the cancer worsening. Bevacizumab, another drug used in some studies, helps stop the tumor from growing by cutting off its blood supply, making it a strong addition in certain cases. Overall, the paclitaxel and carboplatin combination is a reliable choice for treating these cancers. ^{1 3 4 5 6}

Who Is on the Research Team?

John K Chan

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with stage II-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer. Eligible participants must have a certain level of physical fitness (GOG performance status 0-2), adequate organ function, measurable disease, and no prior chemotherapy for abdominal/pelvic tumors. They cannot join if they have certain other health conditions like active bleeding risks or allergies to specific drugs.

Inclusion Criteria

Your white blood cell count is at least 1,500 per microliter.

Your SGOT level must be less than or equal to 3 times the upper limit of normal.

Your blood clotting tests should show normal results.

Exclusion Criteria

You are allergic to Chinese hamster ovary cell products or other genetically engineered antibodies.

I am expecting to undergo or have undergone an invasive procedure.

I am experiencing symptoms of a blockage in my digestive tract.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive paclitaxel and carboplatin with or without bevacizumab. Treatment repeats every 21 days for 6 courses.

18 weeks

6 cycles of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 3 months for 2 years, every 6 months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Paclitaxel

Trial Overview

The study tests how well paclitaxel works when given once every three weeks versus weekly in combination with carboplatin and possibly bevacizumab. Bevacizumab is an antibody that blocks blood vessel growth needed by tumors. The effectiveness of these treatments on various types of ovarian-related cancers is being compared.

How Is the Trial Designed?

Group I: Arm II (neoadjuvant chemotherapy) Experimental Treatment 5 Interventions

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.

Group II: Arm I (adjuvant chemotherapy suboptimally debulked) Experimental Treatment 5 Interventions

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular 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

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 451 patients with advanced ovarian cancer, the combination of Cisplatin, Paclitaxel, and Doxorubicin showed a marginal improvement in progression-free survival (PFS) compared to the standard Carboplatin and Paclitaxel regimen, although there was no difference in overall survival.

The anthracycline combination resulted in better performance status but was associated with a higher incidence of febrile neutropenia, indicating a trade-off between potential benefits and increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel versus cisplatin, paclitaxel and doxorubicin for first-line chemotherapy of advanced ovarian cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Aravantinos, G., Fountzilas, G., Bamias, A., et al.[2022]

The combination of carboplatin and 3-hour infusional paclitaxel was well-tolerated in a study of 92 women with advanced gynecologic cancers, showing a manageable toxicity profile with neutropenia being the most significant side effect.

In patients with ovarian cancer or primary peritoneal carcinoma, 74% experienced a significant decline in tumor marker levels after treatment, indicating strong antineoplastic activity of this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. Markman, M., Kennedy, A., Webster, K., et al.[2015]

In a study involving 247 patients with advanced ovarian cancer, both treatment regimens (standard carboplatin plus paclitaxel and alternating carboplatin/cisplatin plus paclitaxel) showed similar efficacy, with no significant differences in progression-free survival (PFS) or overall survival.

Both regimens were well tolerated, indicating that while the alternating regimen does not provide additional benefits, it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin versus paclitaxel plus alternating carboplatin and cisplatin for initial treatment of advanced ovarian cancer: long-term efficacy results: a Hellenic Cooperative Oncology Group (HeCOG) study. Aravantinos, G., Fountzilas, G., Kosmidis, P., et al.[2022]

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 trial involving 59 women with advanced ovarian cancer, the combination of paclitaxel and carboplatin resulted in a high response rate of 72%, indicating effective treatment for this patient population.

Patients experienced significant improvements in quality of life during the outpatient treatment, with median survival times of 30.1 months for those with measurable disease, suggesting that this regimen is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient taxol and carboplatin chemotherapy for suboptimally debulked epithelial carcinoma of the ovary results in improved quality of life: an Eastern Cooperative Oncology Group Phase II Study (E2E93). Schink, JC., Weller, E., Harris, LS., et al.[2015]

In the GOG-0218 phase III trial involving 751 patients with advanced epithelial ovarian cancer, the addition of bevacizumab to standard chemotherapy significantly improved progression-free survival (PFS) but did not extend overall survival (OS).

High levels of the inflammatory cytokine IL6 were predictive of a therapeutic benefit from bevacizumab, with patients showing longer PFS (14.2 months vs. 8.7 months) and OS (39.6 months vs. 33.1 months) compared to those receiving placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218. Alvarez Secord, A., Bell Burdett, K., Owzar, K., et al.[2023]

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]

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

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A Study to Evaluate the Safety of KAND567 ...

The study is a multicenter, Phase Ib/IIa, open-label, dose-escalation study to evaluate the safety and tolerability of orally administered KAND567 in ...