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

Trial Summary

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.

What data supports the idea that Bevacizumab Dosing for Ovarian Cancer (also known as: Bevacizumab, Avastin) is an effective drug?

The available research shows that Bevacizumab, when added to chemotherapy, significantly extends the time patients live without their cancer getting worse. This was seen in several studies, including GOG 218 and ICON7, where it was used as a first treatment for advanced ovarian cancer, and in the OCEANS study for patients whose cancer returned. In the AURELIA trial, Bevacizumab also helped patients with cancer that didn't respond to other treatments. While it doesn't necessarily make patients live longer overall, it does improve their quality of life by reducing symptoms like abdominal pain. Compared to chemotherapy alone, Bevacizumab offers a better chance of controlling the disease for a longer period. ^{1 2 3 4 5}

What safety data exists for Bevacizumab in treating ovarian cancer?

Bevacizumab, also known as Avastin, has been evaluated in multiple clinical trials for ovarian cancer. Phase II and III trials have shown that while it improves progression-free survival, it is associated with adverse events such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal issues. Most of these side effects are mild and manageable, but some, like arterial thromboembolism and gastrointestinal perforation, can be serious. The safety profile is consistent across studies, and ongoing research aims to optimize patient selection to maximize benefits and minimize risks. ^{2 6 7 8 9}

Is the drug Bevacizumab (Avastin) a promising treatment for ovarian cancer?

Yes, Bevacizumab (Avastin) is a promising drug for treating ovarian cancer. It has been shown to improve progression-free survival, which means it can help keep the cancer from getting worse for a longer time. It also improves the quality of life for patients by reducing symptoms like abdominal discomfort. Bevacizumab is used in combination with other chemotherapy drugs and is effective in both newly diagnosed and recurrent cases of ovarian cancer. ^{2 3 4 10 11}

What is the purpose of this trial?

A pragmatic, two armed, study comparing 2 standard doses of an anti-cancer drug called bevacizumab, given in combination with Chemotherapy. The study will be offered to ovarian cancer patients whose disease is platinum chemotherapy resistant . Higher doses of anti-cancer based drugs are not always better than lower doses and can cause more side effects without improvement of cancer. These patients will be randomly assigned either 7.5 mg/kg or 15mg/kg of bevacizumab combined with chemotherapy . Comparing these two doses will determine if the lower dose-level is non-inferior, and could lead to practice changes.

Research Team

Jenny Ko

Principal Investigator

BC Cancer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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-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]

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]

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, 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 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]

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]

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]

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]

References

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

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

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

Bevacizumab in ovarian cancer: A critical review of phase III studies. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Integrating bevacizumab into the management of epithelial ovarian cancer: the controversy of front-line versus recurrent disease. [2020]

4. 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]

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

Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. [2022]

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

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

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

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

Vertebral artery dissection and cerebral infarction in a patient with recurrent ovarian cancer receiving bevacizumab. [2021]

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

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

10. United States 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. [2022]

11. Cyprus 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. [2021]