Immunotherapy + Chemotherapy for Ovarian Cancer

No longer recruiting at 4 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Severe systemic disease, 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

Compensation: Varies

Number of Visits: 26

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining immunotherapy and chemotherapy can more effectively treat advanced ovarian, primary peritoneal, or fallopian tube cancer. It tests pembrolizumab, an immunotherapy drug that helps the immune system attack cancer, with carboplatin and paclitaxel, chemotherapy drugs that stop cancer cells from growing. The trial targets individuals with stage III-IV high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer who have not undergone more than four cycles of chemotherapy and have a measurable tumor. Participants will undergo multiple cycles of treatment, surgery, and maintenance therapy. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on certain treatments like immunosuppressive therapy or have recently received chemotherapy, you may need to stop or adjust those before joining the trial. 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 using pembrolizumab with carboplatin and paclitaxel is generally safe for patients with advanced ovarian cancer. Studies have found that this combination can be used without major safety issues. In one study, patients took these three drugs together and then continued with just pembrolizumab for ongoing treatment. The results showed this method did not affect safety.

However, like many cancer treatments, some side effects may occur. Common ones include tiredness, nausea, and low blood cell counts, which are typical for chemotherapy. The immunotherapy drug pembrolizumab can also cause immune-related side effects, but these are usually manageable.

Overall, this treatment combination is well-tolerated, and research supports its safety for patients with advanced ovarian cancer. Potential participants should discuss the risks and benefits with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for ovarian cancer?

Researchers are excited about combining immunotherapy with chemotherapy for ovarian cancer because it offers a new way to enhance the body's immune response against cancer cells. While the standard of care typically involves chemotherapy drugs like carboplatin and paclitaxel, this treatment adds pembrolizumab, an immunotherapy drug. Pembrolizumab works by blocking a protein called PD-1, which often helps cancer cells evade the immune system. This unique mechanism could potentially lead to better outcomes by not only attacking cancer cells directly through chemotherapy but also by empowering the immune system to fight cancer more effectively. This dual approach may improve the effectiveness of treatment and provide new hope for patients with ovarian cancer.

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

Research has shown that using pembrolizumab with carboplatin and paclitaxel, the combination tested in this trial, may help treat advanced ovarian cancer. In one study, 55% of patients experienced a complete response, meaning their cancer was undetectable after treatment. Another study found that this combination helped patients live longer, especially those with certain tumor features. However, not all studies indicated an increase in the time during which the cancer did not worsen. Overall, this treatment has demonstrated significant benefits for some patients, particularly those with specific tumor markers. ^{2 6 7 8 9}

Who Is on the Research Team?

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced stage III-IV ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants can have had up to four prior chemo cycles and must be planning on dose-dense chemotherapy with carboplatin and paclitaxel. They should not have received other recent cancer treatments, must show measurable disease, and have a good performance status (0 or 1). Women of childbearing potential need to use birth control and cannot be pregnant.

Inclusion Criteria

Your platelet count is at least 100,000 per microliter.

My cancer is a high-grade type that started in the ovary, peritoneum, or fallopian tube and is not mucinous.

I've had 4 or fewer chemotherapy treatments for advanced ovarian, peritoneal, or fallopian tube cancer.

Exclusion Criteria

I had cancer before, but it was either treated over 5 years ago, was a non-threatening skin cancer, or was early-stage endometrial cancer.

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

My brain metastases are stable, and I haven't used steroids in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy (NACT)

Patients receive paclitaxel and carboplatin intravenously over 21-day cycles for 3 cycles, followed by surgery

9 weeks

3 cycles, each with multiple visits

Adjuvant Therapy

Beginning 3-6 weeks after surgery, patients receive paclitaxel, carboplatin, and pembrolizumab intravenously over 21-day cycles for 3 cycles

9 weeks

3 cycles, each with multiple visits

Maintenance Therapy

Patients receive pembrolizumab intravenously every 21 days for up to 20 cycles

up to 60 weeks

Up to 20 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview

The study tests the effectiveness of pembrolizumab combined with carboplatin and paclitaxel in treating certain cancers. Pembrolizumab is an immunotherapy drug that may boost the immune system's response against cancer cells. Carboplatin and paclitaxel are chemotherapy drugs aimed at stopping tumor growth by killing or preventing cell division.

How Is the Trial Designed?

Group I: Treatment (carboplatin, paclitaxel, and pembrolizumab) Experimental Treatment 5 Interventions

NACT: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8, and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

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 pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

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]

In a study of 735 women treated with carboplatin for gynecological cancers, 10.2% experienced hypersensitivity reactions, with the incidence increasing significantly over the years from 0.88% in 2006 to 5.42% in 2013.

Risk factors for these reactions included advanced disease stage, specific cancer histologies, presence of malignant ascites, and a history of other drug allergies, suggesting that careful monitoring and potential preventive measures, like adjusting infusion rates and using desensitization protocols, could help manage these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies. Tai, YH., Tai, YJ., Hsu, HC., et al.[2020]

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 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]

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Merck Announces Phase 3 KEYNOTE-B96 Trial Met ...

KEYNOTE-B96 is the first trial of an immune checkpoint inhibitor-based treatment regimen in platinum-resistant recurrent ovarian cancer to ...

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NCT03740165 | Study of Chemotherapy With ...

The purpose of this study is to assess the efficacy and safety of treatment with carboplatin/paclitaxel* PLUS pembrolizumab (MK-3475) and maintenance olaparib ...

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Updated survival analysis from OVATION-2 trial.

IMNN-001 demonstrated trends towards material improvement in overall survival and acceptable safety in advanced EOC, especially in HRD+ patients.