Chemotherapy + Immunotherapy for Recurrent Ovarian Cancer

Not currently recruiting at 1070 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining specific chemotherapy and immunotherapy treatments for ovarian, fallopian tube, or primary peritoneal cancer that has returned. Researchers are testing combinations of pegylated liposomal doxorubicin hydrochloride (a type of chemotherapy), atezolizumab (an immunotherapy drug also known as Tecentriq), and bevacizumab (an immunotherapy drug also known as Avastin) to determine which best stops cancer growth and spread. The trial seeks participants with high-grade, recurrent ovarian cancer resistant to platinum-based treatments who have tried 1-2 prior therapies. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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.

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

Research has shown that pegylated liposomal doxorubicin hydrochloride (PLD) is generally safe for treating ovarian cancer. It is already in use for this condition, and patients often tolerate it well, even over extended periods, indicating a history of safety.

Studies on atezolizumab have found it to be well-tolerated when combined with other drugs. Atezolizumab, an immunotherapy, helps the immune system fight cancer and is already approved for other cancer types.

Bevacizumab, another drug in the trial, is a monoclonal antibody used to treat various cancers. It is usually well-tolerated, though some patients might experience side effects like high blood pressure or tiredness.

These studies have identified no major safety concerns. However, when drugs are used together, as in this trial, doctors will closely monitor for any new side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for recurrent ovarian cancer because they combine chemotherapy and immunotherapy in a novel way. Atezolizumab, an immune checkpoint inhibitor, boosts the immune system's ability to attack cancer cells, unlike standard chemotherapy alone. Bevacizumab, an anti-angiogenic drug, works by cutting off the blood supply to tumors, which is a different approach from typical chemotherapy. By combining these drugs with pegylated liposomal doxorubicin hydrochloride, the treatments aim to enhance effectiveness and potentially improve outcomes for patients who have limited options with current therapies.

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

Studies have shown that pegylated liposomal doxorubicin (PLD) can help patients with recurring ovarian cancer live longer. PLD kills cancer cells and prevents their spread. In this trial, some participants will receive PLD with atezolizumab, an immunotherapy drug that may help the immune system attack cancer cells, potentially enhancing PLD's effects. Others will receive PLD with bevacizumab, which cuts off the blood supply tumors need to grow. Additionally, one treatment arm includes all three drugs: PLD, atezolizumab, and bevacizumab. Research suggests these combinations could effectively treat recurrent ovarian cancer, though scientists continue to study the best ways to use them together. ^{1 4 6 7 8}

Who Is on the Research Team?

Roisin E O'Cearbhaill

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02839707

Study Details | NCT02839707 | Pegylated Liposomal ...

This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10321312/

Pegylated liposomal doxorubicin for relapsed epithelial ...

To evaluate the efficacy and safety of PLD, with or without other anti‐cancer drugs, in women with relapsed high grade epithelial ovarian cancer (EOC). Search ...

3.

bmjoncology.bmj.com

bmjoncology.bmj.com/content/4/1/e000573

Thirty years from FDA approval of pegylated liposomal ...

While PLD has gained a strong foothold in relapsed ovarian cancer and metastatic breast cancer, it has not been extensively tested in primary ( ...

4.

uchicagomedicine.org

uchicagomedicine.org/find-a-clinical-trial/clinical-trial/cirb170986

CLINICAL TRIAL / NCT02839707

This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7945320/

The impact of Pegylated liposomal doxorubicin in recurrent ...

Previous meta-analysis studies suggested that pegylated liposomal doxorubicin (PLD) may improve the survival rate of patients with recurrent ovarian cancer.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02839707

Study Details | NCT02839707 | Pegylated Liposomal ...

This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/17301073/

Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil ...

PLD appears to be safe as long-term maintenance in ovarian cancer and may be important for a continued response.

8.

clinicaltrials.ucsf.edu

clinicaltrials.ucsf.edu/trial/NCT02839707

Pegylated Liposomal Doxorubicin Hydrochloride With ...

This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ...