Immunotherapy + Chemotherapy for Ovarian Cancer

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

31 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of immunotherapy and chemotherapy for ovarian cancer?

Research shows that combining pembrolizumab (an immunotherapy drug) with carboplatin (a chemotherapy drug) can enhance the immune system's ability to recognize and fight ovarian cancer cells, especially in cases where the cancer is resistant to platinum-based treatments. Additionally, paclitaxel, when used with platinum drugs like carboplatin, has been shown to be effective in treating advanced ovarian cancer. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemotherapy safe for treating ovarian cancer?

The combination of paclitaxel and carboplatin has been studied for ovarian cancer, showing some safety concerns like hypersensitivity reactions (allergic reactions) to carboplatin in about 10% of patients, and significant blood-related side effects such as low blood cell counts. However, these side effects are generally considered manageable with proper medical care. ^{3 6 7 8 9}

How is the drug combination of Carboplatin, Paclitaxel, and Pembrolizumab unique for treating ovarian cancer?

This treatment combines traditional chemotherapy drugs (Carboplatin and Paclitaxel) with an immunotherapy drug (Pembrolizumab), which helps the immune system recognize and attack cancer cells. This combination is unique because it targets the cancer in two ways: directly killing cancer cells and boosting the body's immune response against them, which is particularly promising for cases resistant to standard platinum-based therapies. ^{1 2 4 5 10}

What is the purpose of this trial?

This phase II trial studies how well pembrolizumab works when given in combination with carboplatin and paclitaxel in treating patients with stage III-IV ovarian, primary peritoneal, or fallopian tube cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Giving pembrolizumab in combination with carboplatin and paclitaxel may be a better treatment for ovarian, primary peritoneal, or fallopian tube cancer.

Research Team

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

References

1. England 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. [2022]

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

Treatment of ovarian cancer: current status. [2015]

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

A phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advanced-stage ovarian, primary peritoneal, or fallopian tube cancer. [2022]

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

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

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

6. England 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. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies. [2020]

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

Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. [2015]

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

Carboplatin and short-infusion paclitaxel in high-risk and advanced-stage ovarian carcinoma. [2015]

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

The Immune adjuvant properties of front-line carboplatin-paclitaxel: a randomized phase 2 study of alternative schedules of intravenous oregovomab chemoimmunotherapy in advanced ovarian cancer. [2019]