Chemotherapy + Immunotherapy for Recurrent Ovarian Cancer

Recruiting at 1040 trial locations

Overseen By Leon C. Hwang

Age: 18+

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Transplantation, CNS malignancy, 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: 4

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

444 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent). Chemotherapy drugs, such as pegylated liposomal doxorubicin hydrochloride, 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. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. It is not yet known which combination will work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as systemic anticancer therapy within 3 weeks and hormonal therapy within 1 week prior to entering the study. Additionally, you must not take systemic immunosuppressive medications within 2 weeks before starting the trial. Please consult with your doctor to review your current medications and ensure they align with the trial's requirements.

What data supports the effectiveness of the drug combination Atezolizumab, Tecentriq, Bevacizumab, Avastin, Pegylated Liposomal Doxorubicin Hydrochloride, Doxil, Caelyx, Lipodox for recurrent ovarian cancer?

Research shows that Bevacizumab (Avastin) combined with other drugs like Pegylated Liposomal Doxorubicin (PLD) has shown significant antitumor activity in recurrent ovarian cancer, especially in patients who have already undergone extensive treatment. Bevacizumab is also approved for use with PLD in platinum-resistant ovarian cancer, indicating its effectiveness in difficult-to-treat cases. ^{1 2 3 4 5}

What safety data exists for the combination of chemotherapy and immunotherapy drugs like Atezolizumab, Bevacizumab, and Caelyx in treating ovarian cancer?

Caelyx, a form of chemotherapy, has shown an improved safety profile compared to traditional doxorubicin, with reduced risks of hair loss and low white blood cell counts, though it can cause hand-foot syndrome in some patients. Bevacizumab, used with chemotherapy, can lead to high blood pressure, bleeding, and other side effects, but these are generally manageable by doctors. Both drugs have been studied in ovarian cancer and have shown a balance of benefits and manageable risks. ^{6 7 8 9 10}

What makes the drug combination of Atezolizumab, Bevacizumab, and Pegylated Liposomal Doxorubicin unique for recurrent ovarian cancer?

This drug combination is unique because it combines chemotherapy with immunotherapy, using Atezolizumab to boost the immune system's ability to fight cancer, Bevacizumab to block blood supply to tumors, and Pegylated Liposomal Doxorubicin to directly kill cancer cells, offering a multi-faceted approach to treating recurrent ovarian cancer. ^{1 11 12 13 14}

Research Team

Roisin E O'Cearbhaill

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with recurrent ovarian, fallopian tube, or primary peritoneal cancer that's resistant to platinum-based therapy. Participants must have good general health and psychological ability to complete the study, no more than two prior cancer treatments (excluding certain hormonal therapies), and agree to use contraception due to risks posed by the treatment on pregnancy.

Inclusion Criteria

I have had 1-2 treatments for my condition, not counting hormonal or certain maintenance therapies.

Your bilirubin level should be within a certain range, but if you have a condition called Gilbert disease, a slightly higher level may be allowed.

Your thyroid-stimulating hormone (TSH) levels should be normal, unless you are on thyroid replacement therapy, in which case your TSH should be below a certain level.

Exclusion Criteria

Your heart's pumping ability is less than or equal to 50%, as shown by a special heart test.

I have not had a stroke or mini-stroke in the last 6 months.

I have stable autoimmune hypothyroidism and am on a consistent thyroid hormone dose.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab in 28-day cycles

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

Visits on days 1 and 15 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

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

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab
• Pegylated Liposomal Doxorubicin Hydrochloride

Trial Overview The trial is testing how well a chemotherapy drug called pegylated liposomal doxorubicin hydrochloride works when combined with atezolizumab and/or bevacizumab. These drugs may help stop tumor growth by killing cells or preventing them from dividing or spreading. The effectiveness of different combinations will be compared in patients.

Participant Groups

Group I: Arm II (PLD, bevacizumab, atezolizumab) Experimental Treatment 5 Interventions

Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, bevacizumab IV over 30-90 minutes on days 1 and 15, and atezolizumab IV over 30-60 minutes on days 1 and 15. Patients also undergo CT on study.

Group II: Arm I (PLD, atezolizumab) Experimental Treatment 4 Interventions

Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 and atezolizumab IV over 30-60 minutes on days 1 and 15. (Closed to accrual as of February 09, 2021)

Group III: Arm III (PLD, bevacizumab) Active Control 4 Interventions

Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 and bevacizumab IV over 30-90 minutes on days 1 and 15. Patients also undergo CT on study.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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+

Findings from Research

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]

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 study of 46 patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy over 30 months, the most common adverse events were hypertension (65.2%) and proteinuria (49%), with hypertension typically occurring 2 months after treatment initiation.

Patients with a history of radiation therapy experienced a significantly higher risk of gastrointestinal perforation, indicating that careful consideration is needed when administering bevacizumab to these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy. Yokoyama, Y., Kubo-Kaneda, M., Sunada, K., 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, a targeted therapy for ovarian cancer, has shown significant improvement in progression-free survival when combined with standard chemotherapy, although it does not extend overall survival.

While bevacizumab can lead to adverse effects like hypertension and bleeding, these can generally be managed effectively, and the treatment has been approved in Europe and the U.S. for its benefits, including improved quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of bevacizumab in the treatment of ovarian cancer. Yoshida, H., Yabuno, A., Fujiwara, K.[2018]

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]

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]

Patients with recurrent ovarian cancer are categorized as either platinum-sensitive or platinum-resistant, which influences treatment options; platinum-sensitive patients often benefit from re-treatment with paclitaxel/platinum combinations, while platinum-resistant patients may receive single-agent therapies like altretamine or topotecan.

For platinum-sensitive patients with minimal residual disease, intensive intraperitoneal therapy with cisplatin and paclitaxel shows the most promise for long-term disease-free survival, highlighting the importance of tailored treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory and recurrent ovarian cancer. Alberts, DS.[2005]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers. [2018]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil): experience with long-term maintenance in responding patients with recurrent epithelial ovarian cancer. [2020]

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

Caelyx: phase II studies in ovarian cancer. [2019]

7. Greece pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

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

Critical appraisal of bevacizumab in the treatment of ovarian cancer. [2018]

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

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

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

Innovative therapies for advanced ovarian cancer. [2012]

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

Pharmacotherapy for recurrent ovarian cancer: current status and future perspectives. [2022]

13. Singapore pubmed.ncbi.nlm.nih.gov

Combination therapy of cytotoxic t-lymphocyte-associated antigen 4 (ctla-4) and programmed death 1 (pd 1) blocker, check point inhibitors for treatment of patients with advanced and recurrent epithelial ovarian cancer. [2020]

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

Treatment of refractory and recurrent ovarian cancer. [2005]