Triple Drug Combo for Advanced Ovarian Cancer

Overseen By Amir Jazaeri, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

20 Participants Needed

Trial Summary

What is the purpose of this trial?

To find out if combining pembrolizumab, bevacizumab (or an equivalent biosimilar drug), and low-dose cyclophosphamide can help control high-grade ovarian cancer that has MRD after treatment. The safety of this treatment combination will also be studied.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving certain treatments like systemic chemotherapy, biological therapy, or radiation therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Bevacizumab, Cyclophosphamide, and Pembrolizumab for advanced ovarian cancer?

Bevacizumab has shown positive effects in treating ovarian cancer, especially when used with chemotherapy, as seen in large trials. It is also approved for use in combination with other drugs for platinum-resistant ovarian cancer, indicating its potential effectiveness in challenging cases. ^{1 2 3 4 5}

What safety data exists for the triple drug combo treatment for advanced ovarian cancer?

Bevacizumab, one of the drugs in the combo, has been studied for safety in ovarian cancer and is generally well-tolerated, but it can cause mild side effects like high blood pressure and protein in the urine, and rare serious effects like blood clots and bowel perforation. Pembrolizumab has been evaluated for safety in advanced ovarian cancer, showing it is generally safe, but specific side effects were not detailed in the available research. ^{6 7 8 9 10}

What makes the triple drug combo for advanced ovarian cancer unique?

The triple drug combo for advanced ovarian cancer is unique because it combines bevacizumab, cyclophosphamide, and pembrolizumab, which target different aspects of cancer growth and immune response. Bevacizumab inhibits blood vessel growth in tumors, cyclophosphamide is a chemotherapy drug that kills cancer cells, and pembrolizumab is an immunotherapy that helps the immune system attack cancer cells, offering a novel approach compared to standard platinum-based therapies. ^{1 11 12 13 14}

Research Team

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for women over 18 with high-grade non-mucinous ovarian cancer, who've had surgery and chemo but still have minimal residual disease. They must not have BRCA mutations or HRD-positive tumors, need good organ function, no recent vaccines or other treatments, and can't be pregnant.

Inclusion Criteria

I am a woman over 18 with a specific type of ovarian cancer.

I had surgery to check for cancer after initial treatment was successful.

I have recovered from my recent surgery and am ready to start a new treatment.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I have another cancer that has been treated or progressed in the last 3 years.

I have or had lung inflammation that needed steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pembrolizumab in combination with Bevacizumab and Oral Cyclophosphamide. Each study cycle is 21 days.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bevacizumab
• Cyclophosphamide
• Pembrolizumab

Trial Overview The study tests a combination of pembrolizumab (an immunotherapy), bevacizumab (a drug that inhibits blood vessel growth in tumors), and low-dose cyclophosphamide (a chemotherapy) to see if it controls ovarian cancer better after standard treatment.

Participant Groups

Group I: Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide Experimental Treatment 3 Interventions

Participants will begin receiving the study drug Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide. Each study cycle is 21 days.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Research is focusing on non-cross-resistant drugs like oxaliplatin and topotecan for treating drug-resistant ovarian cancer, with many being tested in combination therapies to improve outcomes.

Innovative strategies such as anticancer vaccines and gene therapy are being explored, highlighting the importance of clinical trials for women with advanced ovarian cancer due to low current cure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative therapies for advanced ovarian cancer. Trimble, EL.[2012]

Despite high initial response rates to surgery and platinum-based chemotherapy in ovarian cancer, most patients experience relapse, highlighting the need for new treatment strategies to improve survival.

Recent phase III trials have shown that the anti-angiogenic agent bevacizumab, when used alongside chemotherapy and as maintenance therapy, can positively impact outcomes in first-line ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal first-line treatment in ovarian cancer. Raja, FA., Chopra, N., Ledermann, JA.[2022]

Recent clinical trials have identified new treatment strategies for advanced ovarian cancer, including the use of intraperitoneal cisplatin, which showed a survival advantage over intravenous cisplatin after optimal surgery.

The combination of paclitaxel and cisplatin has demonstrated a significant survival benefit compared to cisplatin and cyclophosphamide in patients with suboptimally debulked tumors, indicating a shift towards more effective chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Optimal therapeutic strategies in ovarian epithelial cancer in 1997]. Piccart, MJ., Nogaret, JM.[2015]

The combination of docetaxel, oxaliplatin, and bevacizumab as a first-line treatment for advanced ovarian, peritoneal, or fallopian tube cancer showed a promising 12-month progression-free survival rate of 65.7% among 132 patients, with a median progression-free survival of 16.3 months.

The treatment was generally safe, with the most common severe side effects being neutropenia and leukopenia, and only one reported fatal gastrointestinal perforation, indicating no unexpected safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. Herzog, TJ., Monk, BJ., Rose, PG., et al.[2021]

Bevacizumab (Avastin) has been approved for use in combination with other therapies for patients with platinum-resistant ovarian cancer, showing antitumor activity in this challenging setting.

Despite the overall low response rates (around 10%) to treatments for platinum-resistant ovarian cancer, bevacizumab is currently the most studied antiangiogenic therapy, with ongoing research into alternative treatments like tyrosine kinase inhibitors and angiopoietin inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. McClung, EC., Wenham, RM.[2022]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

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]

In a study of 41 women with recurrent ovarian cancer, the combination of bevacizumab and docetaxel showed a 6-month progression-free survival rate of 43.9%, indicating that this treatment can be effective for patients who have relapsed after platinum-based therapy.

The treatment was generally well-tolerated, with common side effects including gastrointestinal issues and fatigue, but no new unexpected toxicities were reported, suggesting it is a safe option for further investigation in recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy. Wenham, RM., Lapolla, J., Lin, HY., et al.[2021]

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]

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]

Docetaxel has shown comparable effectiveness to paclitaxel when combined with carboplatin for treating advanced ovarian cancer, with a potentially better safety profile.

Current treatments for platinum-resistant ovarian cancer are limited, and while some experimental therapies targeting the epidermal growth factor receptor show promise, more research is needed to find effective new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. Costa, SD., von Minckwitz, G., Wernicke, K., et al.[2008]

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]

A 77-year-old woman with platinum-resistant recurrent ovarian cancer achieved long-term disease control for 29 months using a combination therapy of bevacizumab and gemcitabine (BEV + GEM).

This case highlights the potential of BEV + GEM to significantly prolong survival in patients with difficult-to-treat ovarian cancer, marking it as a promising treatment option in this challenging scenario.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum-resistant recurrent ovarian cancer with long survival on bevacizumab and gemcitabine. Komiyama, S., Kugimiya, T., Takeya, C., et al.[2022]

In a study of 424 women with epithelial ovarian cancer, those with BRCA-associated tumors tolerated chemotherapy regimens similarly to those without BRCA mutations, showing no significant differences in toxicity rates such as anemia and nausea.

Despite the known chemosensitivity benefits of BRCA mutations, the median progression-free survival was not significantly different between BRCA-associated and wild type tumors, indicating that BRCA status may not influence treatment outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study. Gillen, J., Miller, A., Bell-McGuinn, KM., et al.[2022]

References

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

Innovative therapies for advanced ovarian cancer. [2012]

2. England pubmed.ncbi.nlm.nih.gov

Optimal first-line treatment in ovarian cancer. [2022]

3. Belgium pubmed.ncbi.nlm.nih.gov

[Optimal therapeutic strategies in ovarian epithelial cancer in 1997]. [2015]

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

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. [2021]

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

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. [2022]

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

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

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

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

A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy. [2021]

9. Cyprus pubmed.ncbi.nlm.nih.gov

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

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

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

11. Germany pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]

12. England pubmed.ncbi.nlm.nih.gov

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. [2022]

13. Australia pubmed.ncbi.nlm.nih.gov

Platinum-resistant recurrent ovarian cancer with long survival on bevacizumab and gemcitabine. [2022]

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

Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study. [2022]