Chemotherapy + Bevacizumab for Ovarian & Related Cancers

Recruiting at 633 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

692 Participants Needed

Trial Summary

What is the purpose of this trial?

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 bevacizumab in treating patients with stage II, III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is a type of drug called a monoclonal antibody and blocks tumor growth by stopping the growth of blood vessels that tumors need to grow. It is not yet known whether giving paclitaxel with combination chemotherapy once every three weeks is more effective than giving paclitaxel once a week in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

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.

What data supports the effectiveness of the drug combination of chemotherapy and Bevacizumab for ovarian cancer?

Research shows that adding Bevacizumab to the chemotherapy drugs paclitaxel and carboplatin can improve progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in patients with advanced ovarian cancer, although it does not extend overall survival (the time from diagnosis or start of treatment that patients are still alive). ^{1 2 3 4 5}

Is the combination of chemotherapy and Bevacizumab safe for treating ovarian cancer?

The combination of chemotherapy drugs like carboplatin and paclitaxel with Bevacizumab is generally considered safe but can have side effects. Common side effects include high blood pressure, blood clots, bleeding, and joint pain. Some patients may also experience low blood cell counts, fatigue, and nerve damage, but these are usually manageable with medical supervision. ^{1 6 7 8 9}

What makes the chemotherapy plus bevacizumab treatment for ovarian cancer unique?

This treatment combines bevacizumab, a drug that inhibits blood vessel growth in tumors, with the standard chemotherapy drugs carboplatin and paclitaxel. This combination has shown improved outcomes in advanced ovarian cancer compared to chemotherapy alone, offering a novel approach by targeting the tumor's blood supply. ^{1 2 5 10 11}

Research Team

John K Chan

Principal Investigator

NRG Oncology

Eligibility Criteria

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.

My nerve damage symptoms are mild or not present.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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 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]

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]

References

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

Treatment of ovarian cancer: current status. [2015]

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

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

3. United States 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). [2015]

4. United States 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. [2023]

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

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

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

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

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

Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. [2015]

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

Paclitaxel (Taxol)/carboplatin combination chemotherapy in the treatment of advanced ovarian cancer. [2015]

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

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. [2015]

10. England 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. [2022]

11. England 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. [2022]