Chemotherapy +/− Bevacizumab for Ovarian Cancer

Not currently recruiting at 826 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunotherapy, Radiotherapy

Disqualifiers: More than one chemo regimen, 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: 10

Duration: 18-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding bevacizumab (Avastin) to a combination of chemotherapy drugs such as carboplatin, paclitaxel, and gemcitabine hydrochloride is more effective in treating certain types of ovarian cancer that have recurred after surgery. Bevacizumab, an immunotherapy drug, may help the immune system fight cancer, while the chemotherapy drugs work to stop cancer cells from growing and spreading. Patients who have had a complete response to initial chemotherapy for ovarian, peritoneal, or fallopian tube cancer and now have recurrent disease might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking 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 maintenance biological or hormonal therapy, you are eligible as long as your recurrence is documented more than 6 months from the completion of primary chemotherapy and at least 4 weeks have passed since your last infusion of biological therapy.

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

Research has shown that combining bevacizumab with chemotherapy is generally well-tolerated. In a study involving Japanese patients with advanced ovarian cancer, this combination proved manageable. However, adding bevacizumab can increase certain risks. For instance, another study found that using carboplatin, paclitaxel, and bevacizumab together extended the time patients lived without cancer progression, but it also heightened the risk of some side effects.

Regarding the combination of gemcitabine and carboplatin, research indicates it is a safe option for treating recurrent ovarian cancer. One study demonstrated that patients using gemcitabine and carboplatin experienced longer periods without cancer progression.

When gemcitabine, carboplatin, and bevacizumab are used together, the treatment is effective, with manageable side effects similar to those seen in earlier studies. Overall, these treatments have been studied sufficiently to show they are generally safe, though they may come with some risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ovarian cancer because they explore the potential benefits of adding bevacizumab to existing chemotherapy regimens. Bevacizumab is a targeted therapy that works by inhibiting blood vessel growth in tumors, potentially enhancing the effectiveness of chemotherapy drugs like paclitaxel, docetaxel, and gemcitabine hydrochloride. Unlike standard chemotherapy alone, these treatment combinations could improve outcomes by attacking the cancer in multiple ways simultaneously. Additionally, the inclusion of bevacizumab may offer new hope for patients by potentially extending progression-free survival and improving overall effectiveness against ovarian cancer.

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

Research has shown that combining paclitaxel and carboplatin, often with docetaxel, effectively treats advanced ovarian cancer. This trial includes an arm where participants receive this standard treatment. Adding bevacizumab to this mix, as in another arm of this trial, may offer additional benefits, especially for advanced ovarian cancer.

Similarly, using gemcitabine with carboplatin, another treatment arm in this trial, has significantly improved progression-free survival compared to carboplatin alone. Another arm of this trial explores adding bevacizumab to this combination, which studies suggest is promising, particularly for recurrent ovarian cancer. These treatments work by either killing cancer cells or stopping them from growing and spreading. Bevacizumab may enhance these effects by boosting the body's immune response. ^{5 6 7 8 9}

Who Is on the Research Team?

Robert L Coleman

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with recurrent ovarian, epithelial, primary peritoneal, or fallopian tube cancer who responded well to initial platinum-taxane therapy and had a treatment-free period of at least 6 months. They must have measurable disease and be in good physical condition (GOG performance status of 0-2). Exclusions include those with more than one prior chemo regimen, previous radiotherapy to the abdomen/pelvis, certain other cancers within the last 5 years, severe medical problems unrelated to cancer, significant bleeding risks or CNS disease.

Inclusion Criteria

My cancer is of a specific type affecting the lining of organs.

My cancer responded completely to my initial platinum-taxane therapy.

I am receiving or have received initial treatment that includes maintenance therapy after a complete response.

Exclusion Criteria

I will start treatment with bevacizumab in my second cycle after surgery to reduce my tumor.

Patients with specific known hypersensitivity are excluded

I am currently receiving immunotherapy or radiotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Eligible patients undergo abdominal exploration with cytoreduction

1 week

1 visit (in-person)

Treatment

Patients receive chemotherapy with or without bevacizumab, repeating every 21 days for 6-8 courses

18-24 weeks

Every 3 weeks (in-person)

Maintenance

Patients in Arm II receive maintenance bevacizumab every 3 weeks

Varies based on response

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

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

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Gemcitabine Hydrochloride
• Paclitaxel

Trial Overview

The study tests if combining chemotherapy drugs carboplatin, paclitaxel and gemcitabine hydrochloride with the immunotherapy drug bevacizumab is more effective post-surgery than chemotherapy alone for treating recurrent ovarian-related cancers. Patients are randomly assigned to receive either just chemo or chemo plus bevacizumab after surgery.

How Is the Trial Designed?

Group I: Arm IV (gemcitabine hydrochloride, bevacizumab, carboplatin) Experimental Treatment 5 Interventions

Patients receive gemcitabine hydrochloride IV as in Arm III, bevacizumab IV and carboplatin IV as in Arm II.

Group II: Arm III (gemcitabine hydrochloride, carboplatin) Experimental Treatment 4 Interventions

Patients receive gemcitabine hydrochloride IV over 60 minutes on days 1 and 8 and carboplatin as in Arm I.

Group III: Arm II (paclitaxel, docetaxel, carboplatin, bevacizumab) Experimental Treatment 6 Interventions

Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days.

Group IV: Arm I (paclitaxel, docetaxel, carboplatin) Active Control 5 Interventions

Patients receive paclitaxel IV over 3 hours or docetaxel IV over 1 hour and carboplatin over 30 minutes on day 1. Treatment repeats every 21 days.

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]

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]

Combining Bevacizumab (Bev) with standard chemotherapy significantly improves progression-free survival (PFS) and overall survival (OS) in newly diagnosed ovarian cancer patients, with a notable effect size (HR for OS of 0.87) based on data from 2 trials involving 2776 patients.

While both doses of Bev (7.5 mg/kg and 15 mg/kg) showed similar efficacy in PFS and OS, the higher dose was associated with increased toxicities, suggesting that the lower dose may be the safer and more optimal choice for patients at high risk for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis. Zhou, M., Yu, P., Qu, X., et al.[2021]

In a phase 3 trial involving 682 patients with recurrent ovarian cancer, the combination of carboplatin-pegylated liposomal doxorubicin and bevacizumab showed a median progression-free survival of 13.3 months, significantly longer than the 11.6 months observed with the standard carboplatin-gemcitabine-bevacizumab regimen (p=0.012).

The safety profile was comparable between the two treatment groups, with hypertension and neutropenia being the most common severe adverse events; however, treatment-related deaths were rare, occurring in less than 1% of patients in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Pfisterer, J., Shannon, CM., Baumann, K., et al.[2022]

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 of 158 patients with platinum-resistant ovarian cancer, gemcitabine was found to be the most effective chemotherapy agent for those with clear cell or mucinous carcinoma, achieving a median time to treatment failure of 5.3 months, while nedaplatin showed the least effectiveness with only 1.4 months.

The efficacy of nedaplatin varied significantly based on the platinum-free interval, showing better outcomes in patients with a platinum-free interval of 3 months or more, highlighting the importance of individual patient characteristics in chemotherapy selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneous effects of cytotoxic chemotherapies for platinum-resistant ovarian cancer. Nara, K., Taguchi, A., Yamamoto, T., et al.[2023]

Gemcitabine has shown promising results as a single-agent treatment for platinum-resistant ovarian cancer, achieving remission rates of nearly 20% with a favorable safety profile.

Combining gemcitabine with carboplatin has been explored in phase I and II trials, showing potential for improved efficacy in treating ovarian cancer, and further combinations with other agents are being actively researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in ovarian cancer. Orlando, M., Mandachain, M.[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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37024239/

Efficacy and toxicity of carboplatin and gemcitabine ...

The response rates were 69.3% for day 1&8-completed, 67.5% for day 1&8-dropped, and 67.6% for day 1-only (p=0.92). Median progression-free ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0090825819315471

Gemcitabine for recurrent ovarian cancer - a systematic ...

Difference in overall survival was non-significant, but progression-free survival was longer with gemcitabine and carboplatin (HR: 0.72, 95% CI 0.58–0.9). One ...

3.

cancernetwork.com

cancernetwork.com/view/fda-approves-gemzarcarboplatin-advanced-ovarian-ca

FDA Approves Gemzar/Carboplatin for Advanced Ovarian Ca

Gemzar/carboplatin patients had a significantly longer progression-free survival than those on carboplatin alone (median 8.6 months vs 5.8 months, P = .0038.) ...

4.

gynecologiconcology-online.net

gynecologiconcology-online.net/article/S0090-8258(19)31547-1/abstract

Gemcitabine for recurrent ovarian cancer - a systematic ...

One study compared gemcitabine and carboplatin to gemcitabine, carboplatin and bevacizumab. Overall survival was similar in the two arms.

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/15839957/

Combination therapy with gemcitabine and carboplatin in ...

Patients treated with gemcitabine-carboplatin reported significantly faster palliation of abdominal symptoms and a significantly improved global quality of life ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31604664/

Gemcitabine for recurrent ovarian cancer - a systematic ...

Difference in overall survival was non-significant, but progression-free survival was longer with gemcitabine and carboplatin (HR: 0.72, 95% CI 0.58-0.9). One ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/209604s011lbl.pdf

gemcitabine injection - accessdata.fda.gov

In a randomized trial in women with ovarian cancer (Study 1), 175 women received gemcitabine with carboplatin, of which 29% were age 65 years or older.

8.

mayoclinic.org

mayoclinic.org/drugs-supplements/gemcitabine-intravenous-route/description/drg-20066935

Gemcitabine (intravenous route) - Side effects & uses

Gemcitabine interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells may also be affected by ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02627443

Study Details | NCT02627443 | Carboplatin, Gemcitabine ...

This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and berzosertib when given together with carboplatin in treating ...