Pembrolizumab + Carboplatin for Recurrent Gynecologic Cancer

Overseen By Kris Kauno

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Active infection, 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

Compensation: Varies

Number of Visits: 7

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, pembrolizumab and carboplatin, to evaluate their effectiveness in treating ovarian, fallopian tube, or primary peritoneal cancer that has recurred after treatment. Pembrolizumab, an immunotherapy, helps the immune system target cancer cells, while carboplatin, a chemotherapy drug, stops cancer cells from growing and spreading. The goal is to determine if using these drugs together is more effective than other treatments. This trial suits those diagnosed with one of these cancers, who have undergone chemotherapy with platinum-based drugs, and have experienced a significant increase in their cancer marker (CA-125) after previous treatments. As a Phase 2 trial, the research focuses on measuring 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 if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop or adjust it before starting 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 patients with recurring cancers generally tolerate the combination of pembrolizumab and carboplatin well. Studies have found this combination effective in treating recurring ovarian cancer that resists standard treatments, making it beneficial for some difficult-to-treat cancers.

Specifically, when combined with a low dose of carboplatin, pembrolizumab is usually well-tolerated, meaning most patients do not experience severe side effects. However, as with any treatment, some patients might still encounter side effects, so discussing potential risks with a doctor is important.

Overall, current evidence suggests this treatment combination holds promise for managing recurring gynecologic cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and carboplatin for recurrent gynecologic cancer because it offers a unique dual approach. Pembrolizumab is an immunotherapy drug that works by unleashing the immune system to fight cancer cells, while carboplatin is a chemotherapy agent that disrupts cancer cell division. This combination could enhance the overall effectiveness by both directly attacking cancer cells and boosting the body's immune response. Unlike traditional treatments that rely solely on chemotherapy, this combination has the potential to provide a more robust and sustained attack on cancer, potentially leading to better outcomes for patients.

What evidence suggests that pembrolizumab and carboplatin might be effective for recurrent gynecologic cancer?

Research has shown that using pembrolizumab with carboplatin, the combination tested in this trial, might help treat recurring gynecologic cancers. In studies with patients who had advanced or returning endometrial cancer, this combination significantly slowed the cancer's growth. Pembrolizumab helps the body's immune system fight cancer cells, while carboplatin is a chemotherapy drug that kills or stops these cells from growing. Together, they may provide a stronger defense against cancer recurrence or spread. Early evidence suggests they could also benefit similar recurring cancers, such as ovarian, fallopian tube, or primary peritoneal cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

John B. Liao

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who've had platinum-based chemo. They must have a certain level of CA-125 antigen and no measurable disease by specific criteria. Participants need to be sexually active individuals agreeing to contraception, have a life expectancy over 3 months, good performance status (0 or 1), and meet blood count and organ function requirements.

Inclusion Criteria

Total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 X ULN (performed within 14 days of treatment initiation)

My blood clotting time is normal or managed with medication.

I have ovarian, fallopian tube, or peritoneal cancer and have had chemotherapy including platinum-based treatment.

Exclusion Criteria

I haven't had cancer treatment in the last 2 weeks or have recovered from its side effects.

I have stable brain metastases, not on steroids for 14 days, and no carcinomatous meningitis.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive carboplatin IV on day -2 of cycle 1 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 years.

Up to 2 years

Every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days, then every 3 months for year 1, and every 6 months for year 2.

2 years

1 visit at 30 days, then every 3 months for year 1, every 6 months for year 2

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Pembrolizumab

Trial Overview The trial tests pembrolizumab (an immunotherapy drug) combined with carboplatin (a chemotherapy drug) on patients whose cancer has returned. Pembrolizumab may boost the immune system's attack on cancer cells while carboplatin aims to stop tumor growth by killing cells or preventing their division.

How Is the Trial Designed?

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

Patients receive carboplatin IV over 30 minutes on day -2 of cycle 1 only. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI throughout the trial. Patients also undergo blood sample collection on the trial.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Carboplatin is as effective as cisplatin for treating advanced ovarian cancer but has a better safety profile, showing lower rates of side effects like ototoxicity, neuropathy, and nephropathy.

In patients with good kidney function and without severe myelosuppression, carboplatin doses can be increased, suggesting it may become the preferred treatment option over cisplatin in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of carboplatin. Alberts, DS.[2013]

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]

In a phase II study involving 22 patients with BRCA1/2-related metastatic breast cancer, the combination of pembrolizumab and carboplatin showed an overall response rate (ORR) of 43% and a disease control rate (DCR) of 76%, indicating some level of efficacy, particularly in luminal tumors.

Despite the promising results, the study did not meet its primary aim of achieving an ORR of 70%, leading to its termination; however, the safety profile was acceptable with only 22.7% of patients experiencing grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). Cortesi, L., Venturelli, M., Cortesi, G., et al.[2023]

In a study of 113 Japanese patients with gynecologic malignancies, the incidence of hypersensitivity reactions (HSRs) to carboplatin was found to be 8.85%, with all initial reactions being mild, but the risk of severe reactions increased significantly after more than 15 treatment cycles or 8000 mg of the drug.

Patients with ovarian carcinoma experienced a higher rate of HSRs compared to those with uterine carcinoma, highlighting the need for careful monitoring and management of HSRs, especially in patients receiving prolonged carboplatin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Carboplatin-related hypersensitivity reactions in Japanese patients with gynecologic malignancies. Koshiba, H., Hosokawa, K., Kubo, A., et al.[2018]

In a phase II study involving 46 patients with advanced endometrial cancer, the combination of pembrolizumab with carboplatin and paclitaxel resulted in a high objective response rate (ORR) of 74.4%, significantly exceeding the historical control rate of 50%.

The treatment was generally well-tolerated, with common mild side effects like anemia and fatigue, while immune profiling indicated that responders had enriched CD8+ and CD4+ T cell populations, suggesting a potential mechanism of action related to immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium. Barber, EL., Chen, S., Pineda, MJ., et al.[2023]

Carboplatin desensitisation therapy was successful in 93.4% of scheduled cycles, allowing patients with hypersensitivity reactions to continue receiving treatment for gynaecological cancer.

The therapy resulted in an 82.6% therapeutic response rate and a 95.7% disease control rate, demonstrating its efficacy and safety, as no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Adverse Events of Carboplatin Desensitisation Therapy for Gynaecological Cancer: A Retrospective Study. Yamamoto, A., Kamoi, S., Matsuda, S., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

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 involving 356 patients with platinum-sensitive recurrent ovarian cancer, the gemcitabine-carboplatin combination significantly improved progression-free survival (PFS) to 8.6 months compared to 5.8 months for carboplatin alone, indicating its efficacy as a treatment option.

Patients receiving gemcitabine-carboplatin also reported faster relief from abdominal symptoms and a better overall quality of life, suggesting that this regimen may be better tolerated and more beneficial for patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with gemcitabine and carboplatin in recurrent ovarian cancer. Pfisterer, J., Vergote, I., Du Bois, A., et al.[2022]

Citations

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5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2829929

Pembrolizumab in Patients With Advanced Clear Cell ... Pembrolizumab showed clinical benefit in patients with previously treated advanced CCGC, warranting further evaluation in a randomized clinical trial.

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Pembrolizumab with low-dose carboplatin for recurrent ... Pembrolizumab with carboplatin was well-tolerated and active in recurrent platinum-resistant ovarian cancer.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596607/

Clinical Review - Pembrolizumab (Keytruda) - NCBI Bookshelf A phase 2 evaluation of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability. Cancer. 2021;128(6):1206 ...