Bevacizumab Dosing for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Wilfred Hui

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: British Columbia Cancer Agency

Must not be taking: Anti-cancer therapy

Disqualifiers: Other malignancies, Uncontrolled hypertension, Infections, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: up to 4 years

244 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two different doses of the drug bevacizumab (also known as Avastin), administered with chemotherapy, for ovarian cancer that doesn't respond to standard platinum-based chemotherapy. The goal is to determine if a lower dose is as effective as a higher one but with fewer side effects, potentially leading to better treatment plans for patients. The trial seeks participants with ovarian cancer that has resisted prior platinum treatments and who have not previously used bevacizumab. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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. However, you cannot receive concurrent treatment with other anti-cancer therapy or investigational agents. It's best to discuss your specific medications with the trial team.

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

Studies have shown that bevacizumab is generally well-tolerated by patients with ovarian cancer. Over 5,700 patients have participated in research across various cancer types, providing a solid understanding of its safety. Common side effects include high blood pressure and tiredness, but these are usually manageable. For ovarian cancer patients, bevacizumab has been safely used with chemotherapy. Higher doses do not always yield better results and can increase side effects. This study compares two standard doses to determine if the lower dose can be equally effective with fewer side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for ovarian cancer?

Researchers are excited about the bevacizumab treatments for ovarian cancer because they explore different dosing strategies that could improve patient outcomes. While standard treatments often involve a higher dose of bevacizumab at 15mg/kg, one of the trial's approaches uses a lower dose of 7.5mg/kg combined with chemotherapy. This lower dosing could potentially reduce side effects while maintaining effectiveness, making it a promising option for patients who struggle with the intensity of current regimens. By fine-tuning the dose, researchers hope to find a sweet spot that balances efficacy and safety, offering a new angle in the fight against ovarian cancer.

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

Research has shown that bevacizumab effectively treats ovarian cancer. Studies indicate it can extend the period during which the cancer does not worsen by more than six months for patients with advanced ovarian cancer. In this trial, participants will receive either a higher standard dose of bevacizumab (15mg/kg) or a lower standard dose (7.5mg/kg), both combined with chemotherapy. Early findings suggest that the dosage of bevacizumab might not significantly affect outcomes, so lower doses could be as effective as higher ones. Additionally, bevacizumab may help slow cancer progression for about a year, but stopping treatment might lead to faster progression. ^{6 7 8 9 10}

Who Is on the Research Team?

Jenny Ko

Principal Investigator

BC Cancer

Are You a Good Fit for This Trial?

This trial is for adults with advanced, metastatic, or recurrent epithelial ovarian cancer that's resistant to platinum chemotherapy. Participants must have tried at least one chemo regimen including platinum and can't have used anti-angiogenesis inhibitors like bevacizumab before. They should be in good enough health to follow the trial procedures and agree to use effective contraception.

Inclusion Criteria

My cancer got worse within 6 months after platinum-based treatment.

I had radiation therapy, but it's been over 4 weeks since my last dose.

I have had chemotherapy that included platinum and may have had other treatments.

Exclusion Criteria

Pregnancy or breastfeeding

I have an uncontrolled blood clotting issue.

I have had a bowel obstruction or still have one.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 7.5 mg/kg or 15 mg/kg of bevacizumab combined with chemotherapy

up to 4 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months after last dose

Quality of Life Assessment

Quality of life changes are assessed during treatment and 4 weeks after coming off treatment

During treatment and 4 weeks post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab

Trial Overview The study compares two standard doses of bevacizumab (7.5 mg/kg vs. 15 mg/kg) combined with chemotherapy in patients with ovarian cancer who don't respond well to platinum-based treatments. It aims to see if a lower dose is just as effective without causing more side effects.

How Is the Trial Designed?

Group I: Lower standard dosing bevacizumab plus chemotherapy Experimental Treatment 1 Intervention

bevacizumab 7.5mg/kg + chemotherapy

Group II: Higher Standard dosing as per standard regimen Active Control 1 Intervention

bevacizumab 15mg/kg + chemotherapy

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?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Published Research Related to This Trial

Ovarian cancer patients treated with bevacizumab can face serious side effects, highlighting the need for careful monitoring during treatment.

A specific case of vertebral artery dissection was reported in a patient receiving bevacizumab, indicating a potential risk associated with this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vertebral artery dissection and cerebral infarction in a patient with recurrent ovarian cancer receiving bevacizumab. Mantia-Smaldone, GM., Bagley, LJ., Kasner, SE., et al.[2021]

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]

Bevacizumab (BV) has been shown to significantly improve progression-free survival in patients with advanced ovarian cancer when combined with standard chemotherapy, although it does not extend overall survival.

While BV is associated with some adverse events like hypertension and bleeding, these can generally be managed effectively, and it also enhances the quality of life for patients with recurrent ovarian cancer, particularly regarding abdominal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in ovarian cancer: A critical review of phase III studies. Rossi, L., Verrico, M., Zaccarelli, E., et al.[2022]

Bevacizumab, an anti-angiogenic agent, has been approved for use in advanced ovarian cancer and has shown significant efficacy when combined with standard chemotherapy in multiple phase III trials involving women with ovarian cancer.

While bevacizumab's safety profile aligns with expectations, ongoing research is necessary to identify markers that can predict patient response to optimize treatment outcomes, and new anti-angiogenic agents are currently being evaluated in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review. Aravantinos, G., Pectasides, D.[2023]

Bevacizumab, an antiangiogenesis drug, has been approved by the US FDA for use in combination with chemotherapy for women with newly diagnosed ovarian cancer, based on a Phase III clinical trial that demonstrated improved progression-free survival.

The approval extends to both frontline and maintenance therapy for different types of ovarian cancer, including platinum-sensitive and platinum-resistant recurrent cases, highlighting its versatility in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab use in the frontline, maintenance and recurrent settings for ovarian cancer. Haunschild, CE., Tewari, KS.[2023]

Bevacizumab, an anti-VEGF therapy, has shown efficacy in treating epithelial ovarian cancers, both as a standalone treatment and in combination with other therapies, based on evidence from Phase II trials involving various patient populations.

While most side effects of bevacizumab, such as proteinuria and hypertension, are mild and manageable, there are serious but rare risks like arterial thromboembolism and gastrointestinal perforation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with bevacizumab in the management of epithelial ovarian cancer. Burger, RA.[2015]

The AURELIA trial demonstrated that adding bevacizumab to chemotherapy significantly improves progression-free survival (PFS) in patients with platinum-resistant recurrent ovarian cancer, with a median PFS of 8.1 months compared to 3.9 months for chemotherapy alone.

Independent review confirmed the primary findings, showing consistent results between investigator assessments and independent review committee evaluations, reinforcing the efficacy of bevacizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. Husain, A., Wang, Y., Hanker, LC., 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]

In a study of 58 ovarian epithelial cancer patients, the combination of intraperitoneal cisplatin and bevacizumab significantly reduced VEGF levels in ascites and improved overall response rates compared to cisplatin alone (90.32% vs. 59.26%).

Patients receiving the combination treatment also experienced a higher rate of quality of life improvement (93.55% vs. 48.15%), with no serious adverse effects reported, indicating that this treatment is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal administration of cisplatin plus bevacizumab for the management of malignant ascites in ovarian epithelial cancer: results of a phase III clinical trial. Zhao, H., Li, X., Chen, D., et al.[2022]

In a study of 106 patients with relapsed ovarian cancer, the 7.5 mg/kg/3-week dosing of bevacizumab showed similar effectiveness in progression-free survival (PFS) and overall survival (OS) compared to the standard 15 mg/kg/3-week dosing.

Cytoreductive surgery at relapse significantly improved overall survival, and while bevacizumab was associated with some toxicities, the rate of severe hypertension was lower than expected, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Half-dose bevacizumab experience in relapsed ovarian cancer patients in Turkey due to formal regulations: similar effectiveness with lower rate of hypertension. Kose, F., Alemdaroglu, S., Mertsoylu, H., et al.[2021]

Bevacizumab, an anti-VEGF monoclonal antibody, has shown significant efficacy in treating epithelial ovarian cancer (EOC) when added to chemotherapy, as demonstrated in four positive randomized trials involving both front-line and recurrent cases.

The ongoing debate in clinical practice is not whether to use bevacizumab, but rather when to use it, as considerations of efficacy, toxicity, quality of life, and cost-effectiveness play crucial roles in determining the optimal treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating bevacizumab into the management of epithelial ovarian cancer: the controversy of front-line versus recurrent disease. Monk, BJ., Pujade-Lauraine, E., Burger, RA.[2020]

Citations

1. avastin.com avastin.com/hcp/ovar/efficacy-data.html

Avastin® (bevacizumab) Clinical Trials for Ovarian Cancer Ovarian Cancer: Avastin Efficacy Data · Patients achieved a median PFS benefit of >6 months in stage III or IV ovarian cancer after primary surgery · Select ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12372840/

Bevacizumab Efficacy and Tolerability in Patients with ... In our study, we assessed the effects and adverse outcomes linked to the addition of bevacizumab to chemotherapy, along with the influence of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0090825825000915

Comparative efficacy and safety of low-dose versus high ... Despite limitations of small sample size and heterogeneities, findings suggest that bevacizumab dose may not significantly impact ovarian cancer outcomes.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37055754/

Real-world study of bevacizumab treatment in patients with ... Conclusion: Bevacizumab is effective and well-tolerated in the real world setting of ovarian cancer treatment. Adding bevacizumab to NACT is ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2807928

Time-Dependent Changes in Risk of Progression During ... In ovarian cancer, bevacizumab may reduce progression for approximately 1 year after initiation, but discontinuation may increase subsequent progression.

6. avastin.com avastin.com/hcp/ovar/safety.html

Avastin® (bevacizumab) Adverse Events | Ovarian Cancer Learn more about Avastin® (bevacizumab) adverse reactions profile for stage III or IV ovarian cancer, platinum-sensitive ovarian cancer (psOC) ...

7. avastin.com avastin.com/hcp.html

Avastin® (bevacizumab) Efficacy, Safety, Dosing & ... Avastin is extensively studied: Avastin FDA approvals based on 12 pivotal trials across 7 tumor types.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10003828/

Safety Analysis of Bevacizumab in Ovarian Cancer Patients Bevacizumab (BEV) is beneficial for ovarian cancer patients, but the real world's patient settings differ from those in clinical trials.

9. ema.europa.eu ema.europa.eu/en/documents/product-information/avastin-epar-product-information_en.pdf

Avastin, INN-bevacizumab - EMA The overall safety profile of Avastin is based on data from over 5 700 patients with various ... Epithelial ovarian, fallopian tube and primary peritoneal cancer.

10. gene.com gene.com/medical-professionals/medicines/avastin

Avastin® (bevacizumab) - Information for Healthcare ... Safety Data Sheets (2 SDS). AVASTIN(R) Vials (100 mg) · AVASTIN(R) Vials (400 mg). Side Effect Reporting. Report side effects to the FDA at (800) FDA-1088 or ...