Bevacizumab + Anetumab Ravtansine/Paclitaxel for Ovarian Cancer

Recruiting at 28 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Pregnancy, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle, repeated until disease progression or unacceptable toxicity

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies the side effects of bevacizumab and anetumab ravtansine or paclitaxel in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that does not respond to treatment (refractory). Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Anetumab ravtansine is a drug that targets a protein in the body called mesothelin, which can be found in some ovarian, pancreatic and other tumors. Chemotherapy drugs, such as paclitaxel, 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. It is not yet known whether giving bevacizumab and anetumab ravtansine or paclitaxel may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

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

The trial protocol does not specify if you need to stop your current medications, but you cannot take strong inhibitors or inducers of CYP3A4 within 2 weeks before and during the trial. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

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

The combination of Bevacizumab (Avastin) and Paclitaxel has been studied for ovarian cancer, showing some safety concerns. In heavily pre-treated patients, serious side effects like gastrointestinal perforations (holes in the stomach or intestines) and fistulas (abnormal connections between organs) occurred in a small percentage of patients. However, no treatment-related deaths were reported. ^{1 2 3 4 5}

How is the drug combination of Bevacizumab, Anetumab Ravtansine, and Paclitaxel unique for treating ovarian cancer?

This drug combination is unique because it includes Anetumab Ravtansine, which is not commonly used in standard ovarian cancer treatments. Bevacizumab targets blood vessel growth in tumors, while Paclitaxel disrupts cancer cell division, and the addition of Anetumab Ravtansine may offer a novel approach by targeting specific proteins on cancer cells. ^{3 6 7 8 9}

What data supports the effectiveness of the drug combination Bevacizumab + Anetumab Ravtansine/Paclitaxel for ovarian cancer?

Research shows that combining bevacizumab with other drugs like paclitaxel can be effective in treating ovarian cancer, with studies indicating improved survival rates and response in patients. Additionally, similar drug combinations have shown significant activity in recurrent ovarian cancer, suggesting potential benefits for this treatment approach. ^{7 10 11 12 13}

Who Is on the Research Team?

Stephanie Lheureux

Principal Investigator

University Health Network Princess Margaret Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with certain types of ovarian, fallopian tube, or primary peritoneal cancer that have not responded to platinum-based chemotherapy. Participants must have measurable disease progression and be in good enough health to perform daily activities (ECOG <=2). They should not have had recent major surgeries or other treatments and must agree to use contraception if applicable.

Inclusion Criteria

My eligibility is not based on mesothelin levels for the initial phase.

I have a confirmed diagnosis of advanced ovarian, fallopian tube, or primary peritoneal cancer.

My ovarian cancer did not respond well to platinum-based treatments.

Exclusion Criteria

You are currently taking any experimental medications.

I have serious blood vessel problems in my arms or legs.

I do not have an active HIV, hepatitis B, or C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either anetumab ravtansine and bevacizumab or paclitaxel and bevacizumab in 28-day cycles

28 days per cycle, repeated until disease progression or unacceptable toxicity

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

30-37 days initially, then every 8 weeks

Initial follow-up visit, then bi-monthly visits

What Are the Treatments Tested in This Trial?

Interventions

• Anetumab Ravtansine
• Bevacizumab
• Paclitaxel

Trial Overview The study compares the effectiveness of Bevacizumab combined with Anetumab Ravtansine versus Paclitaxel alone in treating refractory cancers. Bevacizumab targets tumor blood supply, Anetumab Ravtansine attacks a specific protein on cancer cells, while Paclitaxel interferes with cell division.

How Is the Trial Designed?

Group I: GROUP II (paclitaxel, bevacizumab) Experimental Treatment 2 Interventions

Patients receive paclitaxel on days 1, 8, 15, and 22 and bevacizumab over 30-90 minutes IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: GROUP I (anetumab ravtansine, bevacizumab) Experimental Treatment 2 Interventions

Patients receive anetumab ravtansine IV over 1 hour on days 1, 8, 15, and 22 and bevacizumab over 30-90 minutes IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of mirvetuximab soravtansine and bevacizumab shows promising efficacy in treating women with recurrent ovarian cancer that has high folate receptor alpha (FRα) expression, achieving a 64% objective response rate.

Patients treated with this combination therapy experienced a median progression-free survival of 10.6 months, indicating a significant benefit regardless of their platinum sensitivity status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Significant Activity" for ADC in Ovarian Cancer. [2022]

In a study of 10 women with advanced, refractory ovarian cancer, treatment with biweekly bevacizumab and weekly taxane chemotherapy resulted in a decrease in CA125 levels for 9 out of 10 evaluable patients, indicating a positive response to therapy.

The treatment was well-tolerated, with mild side effects and no severe toxicities (grade 3 or 4), suggesting that this regimen is safe and warrants further investigation for its efficacy in managing symptoms of ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Cohn, DE., Valmadre, S., Resnick, KE., et al.[2018]

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 study presented at the 2020 ASCO Virtual Scientific Program, the combination of mirvetuximab soravtansine and bevacizumab showed a remarkable overall response rate of 64% in patients with platinum-agnostic ovarian cancer.

This high response rate indicates that this treatment combination may be effective for ovarian cancer patients regardless of their previous response to platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirvetuximab Soravtansine Combination Yields Encouraging Response Rates in Ovarian Cancer. Fowler, M.[2021]

In a study of 164 patients with recurrent ovarian cancer, the combination of bevacizumab (BEV) with paclitaxel and carboplatin significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to the control group receiving only paclitaxel and carboplatin.

The experimental group experienced fewer adverse reactions, such as allergies and gastrointestinal issues, and showed a significant improvement in quality of life after treatment, indicating that BEV combined with paclitaxel is both effective and safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer. Cong, J., Liu, R., Hou, J., et al.[2020]

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 86 patients with platinum-resistant recurrent ovarian cancer, the combination of bevacizumab (BEV) and albumin-bound paclitaxel (ABP) significantly improved the overall response rate (ORR) to 86.0% compared to 62.8% for ABP alone, indicating enhanced treatment efficacy.

Patients receiving BEV + ABP also experienced longer progression-free survival (8.9 months vs. 6.7 months) and overall survival (16.3 months vs. 12.6 months) compared to those treated with ABP alone, with no significant increase in adverse reactions, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Bevacizumab Combined with Albumin-Bound Paclitaxel in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer. Liu, B., An, R., Yu, J.[2020]

Bevacizumab has been shown to be effective in managing epithelial ovarian cancer, particularly when combined with cytotoxic chemotherapy, as indicated by phase III trial data that demonstrate improved progression-free survival.

There is a compelling argument for using bevacizumab as a single agent in patients with platinum-resistant ovarian cancer, suggesting a more rational and potentially cost-effective approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. Markman, M.[2020]

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]

Citations

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

"Significant Activity" for ADC in Ovarian Cancer. [2022]

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

Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. [2018]

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

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

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

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

5. Pakistan pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Combined Chemotherapy Regimens with Bevacizumab in Platinum-sensitive Ovarian Cancers. [2023]

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

Mirvetuximab Soravtansine Combination Yields Encouraging Response Rates in Ovarian Cancer. [2021]

7. Cyprus pubmed.ncbi.nlm.nih.gov

Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer. [2020]

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

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

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

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

10. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy of Bevacizumab Combined with Albumin-Bound Paclitaxel in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer. [2020]

11. England pubmed.ncbi.nlm.nih.gov

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. [2020]

12. 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]

13. England pubmed.ncbi.nlm.nih.gov

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