Chemotherapy + Immunotherapy for Ovarian Cancer

Overseen By Dmitriy Zamarin, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Systemic corticosteroids, Immunosuppressants

Disqualifiers: Other malignancies, Prior radiotherapy, Active infections, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how adding nivolumab (an immunotherapy drug) or nivolumab plus ipilimumab (another immunotherapy drug) affects the standard chemotherapy for advanced high-grade serous cancers of the ovary, fallopian tube, or primary peritoneal area. The typical chemotherapy includes Carboplatin and Paclitaxel. The study will explore whether these new combinations can improve treatment outcomes. Suitable participants have been diagnosed with advanced high-grade serous cancer that requires chemotherapy and surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

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, you cannot participate if you are on certain treatments like other anticancer therapies or high doses of corticosteroids. It's best to discuss your specific medications with the trial team.

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

Research shows that combining nivolumab with carboplatin and paclitaxel is safe and manageable. In one study, most patients who received this treatment underwent successful surgery, and the treatment was generally well-tolerated.

When combined with ipilimumab, nivolumab maintains a promising safety profile. Studies have shown that using both drugs together is more effective than using nivolumab alone for treating recurrent ovarian cancer, indicating that the combination is both effective and manageable.

These treatments are still in early testing for this type of cancer, focusing on understanding their interaction and ensuring safety. Since nivolumab and ipilimumab are already used for other conditions, existing safety information supports their use. However, it is crucial to remember that this is an ongoing process to ensure their safety and effectiveness for ovarian cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemotherapy with immunotherapy for ovarian cancer, as it introduces a fresh approach to treatment. Most current treatments rely heavily on chemotherapy agents like paclitaxel and carboplatin. However, the addition of immunotherapies like nivolumab and ipilimumab aims to boost the body's own immune response to fight the cancer. Nivolumab targets and blocks the PD-1 pathway, enhancing the immune system's ability to detect and destroy cancer cells, while ipilimumab works by activating T-cells. This combination approach could potentially enhance effectiveness and offer new hope for patients with ovarian cancer.

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

This trial will compare different treatment combinations for ovarian cancer. One arm involves adding nivolumab to the usual chemotherapy drugs, carboplatin and paclitaxel. Studies have shown that this combination is safe and can help treat ovarian cancer, with most patients having all visible cancer removed. Another arm will test the combination of nivolumab and ipilimumab with chemotherapy. Previous research found that this combination showed promising results in treating recurring ovarian cancer, with about 63% of patients still alive one year later, regardless of certain cancer characteristics. Overall, these treatments aim to help the immune system fight cancer cells more effectively. ^{1 2 3 4 6}

Who Is on the Research Team?

Carol Aghajanian, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. Participants must be in good physical condition (ECOG Status of 0-2), have not received prior treatment for their cancer, and have adequate organ function. They cannot join if they've had other cancers within the last 3 years, previous radiotherapy to the abdomen/pelvis/thorax, active autoimmune diseases, or are pregnant/nursing.

Inclusion Criteria

My cancer stage fits the study requirements.

I have had a core needle biopsy to confirm my diagnosis before starting treatment.

I have been mostly active and able to care for myself in the last 28 days.

Exclusion Criteria

Unable or unlikely to comply with the dosing schedule and study evaluations

I have or had endometrial cancer that doesn't meet certain conditions.

You have taken experimental medication within the last 28 days or 5 half-lives before starting this clinical trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive nivolumab with or without ipilimumab in combination with dose dense paclitaxel and carboplatin for three cycles, each cycle lasting 3 weeks

9 weeks

3 visits (in-person) per cycle

Surgery

Participants undergo cytoreductive surgery following neoadjuvant treatment

Adjuvant Treatment

Participants receive three more cycles of the same treatment regimen as adjuvant therapy

9 weeks

3 visits (in-person) per cycle

Maintenance

Nivolumab is administered every 4 weeks for up to 12 months

up to 12 months

1 visit (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Ipilimumab
• Nivolumab
• Paclitaxel

Trial Overview The study tests adding Nivolumab alone or combined with Ipilimumab to standard chemotherapy (Carboplatin and Paclitaxel) before surgery in treating these cancers. It aims to see whether this combination improves outcomes compared to chemotherapy alone.

How Is the Trial Designed?

Group I: Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin Experimental Treatment 4 Interventions

Patients will be treated with nivolumab plus ipilimumab plus standard of care dose dense paclitaxel \& carboplatin chemotherapy for 3 cycles (up to a maximum of six), each cycle is 3 weeks, followed by cytoreductive surgery then three more cycles of the same treatment regimen. Paclitaxel 80mg/m2 IV will be administered over approx 1 hour on Days 1,8, \& 15 of each 21 day cycle. Carboplatin AUC6 will be administered as an approx 30 minute IV infusion, following paclitaxel admin on Day 1 of each 21 day cycle. Nivolumab 360mg will be infused IV over approx 30 min on Day 1 of Cycles 1-6 (to 9) of each 21 day cycle. Ipilimumab 1mg/kg will be infused IV over approx 30 min on Day 1 of Cycles 1 \& 3, as well as Cycle 4 \& Cycle 6. Of note, if patients receive more than 3 cycles in the pre-operative setting, then ipilimumab will be administered with the first \& third cycle in the post-operative setting. Nivolumab will then be infused Day 1 of each 28 day maintenance phase cycle.

Group II: Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed) Experimental Treatment 3 Interventions

Patients will be treated with nivolumab plus standard of care dose dense paclitaxel and carboplatin for three cycles, where each cycle is 3 weeks, followed by cytoreductive surgery then three more cycles of the same treatment regimen administered as adjuvant treatment. Paclitaxel 80mg/m2 will be administered over approximately 1 hour as an IV infusion on Days 1,8, and 15 of each 21-day cycle. Carboplatin AUC6 will be administered as approximately a 30 minute IV infusion, following paclitaxel administration on Day 1 of each 21-day cycle. Carboplatin dose calculation instructions can be found in Appendix 4. Nivolumab 360mg will be infused IV over approximately 30min on Day 1 of Cycles 1-6. During the maintenance phase, Nivolumab 480mg will be infused IV on day 1 of each 28 day cycle, for up to 12 months. During the maintenance period, each cycle is 4 weeks.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

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]

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]

Two large trials showed that the combination of paclitaxel and cisplatin is more effective than cisplatin and cyclophosphamide in treating advanced ovarian cancer, leading to higher response rates and longer survival times.

The combination of carboplatin and paclitaxel has similar efficacy to cisplatin and paclitaxel but with reduced toxicity, making it the preferred treatment regimen for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin in the treatment of ovarian cancer. Ozols, RF.[2015]

In a study of 49 patients with advanced epithelial ovarian cancer receiving adjuvant intraperitoneal carboplatin and intravenous dose-dense paclitaxel, the treatment was well-tolerated, with 87.8% completing six cycles of chemotherapy.

The side effects observed, such as neutropenia (32.7%) and the need for red blood cell transfusions (28.6%), were comparable to or better than those reported in traditional treatment regimens, indicating a favorable safety profile for this chemotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Tolerance and Side Effects of Intraperitoneal Carboplatin and Dose-Dense Intravenous Paclitaxel in Ovarian Cancer. Bisch, SP., Sugimoto, A., Prefontaine, M., et al.[2019]

In a study of 7 heavily pre-treated ovarian cancer patients, weekly administration of paclitaxel showed some efficacy, resulting in 2 cases of partial remission and 3 cases with no change in disease status.

Despite some patients experiencing peripheral neuropathy and mild hematological toxicity, the overall treatment was considered effective in maintaining quality of life for patients resistant to previous chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study on the efficacy of weekly paclitaxel administration for platinum-resistant epithelial ovarian carcinoma]. Fujii, K., Takano, M., Okamoto, S., et al.[2015]

In a study of 22 high-risk ovarian cancer patients treated with adjuvant paclitaxel and carboplatin, the treatment was generally well tolerated, with manageable side effects and a high completion rate of therapy (77% without delays).

The treatment led to significant clinical outcomes, with 16 out of 19 patients with advanced disease achieving complete clinical remission after six cycles, indicating strong efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and short-infusion paclitaxel in high-risk and advanced-stage ovarian carcinoma. Coleman, RL., Bagnell, KG., Townley, PM.[2015]

The combination of paclitaxel and carboplatin showed an overall response rate of 42% in 73 patients with advanced ovarian cancer who had previously undergone platinum-based chemotherapy, indicating its efficacy as a treatment option.

While myelosuppression was the most common severe side effect, with significant rates of neutropenia, the therapy was generally well-tolerated, with only one case of febrile neutropenia and manageable levels of other toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens) phase II study. Guastalla, JP., Pujade-Lauraine, E., Weber, B., et al.[2020]

Citations

1. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(25)01044-3/fulltext

A pilot study of nivolumab in combination with neoadjuvant ... We evaluated nivolumab with carboplatin and dose-dense paclitaxel in 21 patients with newly diagnosed ovarian cancer. •. No new safety signals were observed ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825825010443

A pilot study of nivolumab in combination with neoadjuvant ... Conclusions. The combination of nivolumab with carboplatin and paclitaxel was safe and tolerable. Most patients achieved a complete gross resection and one- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03245892

A Study of Carboplatin and Paclitaxel Chemotherapy With ... The purpose of this study is to find out what effects, good or bad, the addition of nivolumab or the combination of nivolumab plus ipilimumab to typical ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7326187/

Immunotherapy For Ovarian Cancer: Recent Advances ... Three patients had SD lasting ≥6 months, yielding a 67% clinical benefit rate. No significant effects of the combination on pharmacokinetic were ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11983808/

Comparative effectiveness and safety of treatment ... Although the initial overall response rate (ORR) is 60–80%, 70% of patients experience recurrence within 3 years [3].

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2015.62.3397

Safety and Antitumor Activity of Anti–PD-1 Antibody, ... The median progression-free survival time was 3.5 months (95% CI, 1.7 to 3.9 months), and the median overall survival time was 20.0 months (95% CI, 7.0 months ...