Cisplatin + Pembrolizumab + Radiation Therapy for Vulvar Cancer

Recruiting in Boston (>99 mi)

Overseen By Oladapo Yeku, MD, PHD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Live vaccines

Disqualifiers: Active infection, Autoimmune disease, CNS metastases, 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: 3

Duration: 36 weeks

24 Participants Needed

Trial Summary

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 have received certain cancer treatments recently, you may need to wait a specific period before starting the trial.

What data supports the effectiveness of the treatment Cisplatin + Pembrolizumab + Radiation Therapy for Vulvar Cancer?

Research suggests that cisplatin can enhance the immune response against tumors, and when combined with radiation, it may increase the effectiveness of pembrolizumab, an immunotherapy drug. Pembrolizumab has shown promise in treating vulvar cancer, with some patients experiencing significant tumor reduction and clinical remission. ^{1 2 3 4 5}

Is the combination of Cisplatin, Pembrolizumab, and Radiation Therapy generally safe for humans?

Studies on Cisplatin with Radiation Therapy for cervical cancer show that while there are some side effects like nausea, vomiting, and anemia (low red blood cell count), the overall safety is considered acceptable. This suggests that Cisplatin with Radiation Therapy is generally safe, but specific safety data for the combination with Pembrolizumab is not provided. ^{6 7 8 9 10}

How is the treatment of Cisplatin, Pembrolizumab, and Radiation Therapy unique for vulvar cancer?

This treatment combines chemotherapy (Cisplatin), immunotherapy (Pembrolizumab), and radiation to enhance the body's immune response against vulvar cancer, which is not typically targeted by immunotherapy. The combination aims to improve outcomes by using Cisplatin to make cancer cells more vulnerable to immune attack and radiation to further stimulate an anti-tumor immune response. ^{1 2 3 4 11}

What is the purpose of this trial?

This research is being done to see how well the combination of a standard of care drug, investigational drug, and radiation therapy work against unresectable vulvar squamous cell carcinoma. This research study involves the following: * Cisplatin (standard of care drug) * Pembrolizumab (investigational drug) * Radiation Therapy (standard of care intervention)

Research Team

Oladapo Yeku, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adult women with vulvar squamous cell carcinoma that can't be removed by surgery or has come back after treatment. They should have measurable disease, an ECOG performance status of 0 or 1, and adequate organ function. Women who are pregnant, breastfeeding, or have had certain treatments recently cannot join.

Inclusion Criteria

I have not had more than two chemotherapy treatments for my recurrent disease, and I stopped immunotherapy only if I had severe side effects.

My cancer can be measured by scans and has grown in previously treated areas.

I have provided a sample of my tumor for testing, not from an area treated with radiation.

Exclusion Criteria

I am currently being treated for an infection.

Pregnant or nursing women.

I have had or currently have lung inflammation treated with steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cisplatin weekly, pembrolizumab every 3 weeks, and daily radiation therapy for up to 8 weeks, followed by maintenance pembrolizumab for a total of 36 weeks

36 weeks

Weekly visits for cisplatin, every 3 weeks for pembrolizumab, daily visits for radiation therapy during the first 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Cisplatin
• Pembrolizumab
• Radiation Therapy

Trial Overview The study tests a combination of Cisplatin (a standard cancer drug), Pembrolizumab (an investigational drug), and Radiation Therapy to treat unresectable vulvar cancer. The goal is to see how effective this trio is compared to current treatments.

Participant Groups

Group I: Pembrolizumab, Cisplatin and Radiation Therapy Experimental Treatment 3 Interventions

Treatment period is 36 weeks with 21 day study cycles. Participants will receive cisplatin at a predetermined dose 1x weekly, pembrolizumab at a predetermined dose every 3 weeks, concurrently with daily radiation therapy from week 1 up to week 8. First 3 participants on the study, may skip 1 or 2 pembrolizumab dosages while receiving radiation therapy. Following completion of daily radiation therapy with 1x weekly cisplatin and 1x every 3 weeks pembrolizumab, participants will continue at a pre-determined maintenance dose of pembrolizumab 1x every 3 weeks for a total of 12 cycles or 36 weeks.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

This study proposes a phase II clinical trial to evaluate the combination of pembrolizumab with cisplatin-sensitized radiation therapy in women with unresectable or metastatic vulvar cancer, aiming to enhance anti-tumor immune responses and improve patient outcomes.

The trial is designed to be accessible, allowing patients to receive standard care locally while monitoring for adverse effects and conducting translational studies to assess immune activation, addressing the lack of effective immunotherapy options for this rare cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of combined chemo-immunotherapy with cisplatin-pembrolizumab and radiation for unresectable vulvar squamous cell carcinoma. Yeku, O., Russo, AL., Lee, H., et al.[2021]

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

In a phase II clinical trial, pembrolizumab showed potential efficacy in treating recurrent or metastatic vaginal and vulvar squamous cell carcinoma (SCC), with one patient experiencing an 81% reduction in tumor size before treatment was discontinued due to disease progression.

The treatment was generally well-tolerated, although one patient experienced grade 3 mucositis, indicating that while pembrolizumab may be beneficial, further studies are necessary to confirm its effectiveness and identify which patients are most likely to respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in vaginal and vulvar squamous cell carcinoma: a case series from a phase II basket trial. How, JA., Jazaeri, AA., Soliman, PT., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, was successfully used to treat a patient with recurrent vulvar cancer, leading to complete clinical remission after just 2 cycles of treatment.

The patient showed a significant response after 6 cycles, and a CT scan 10 weeks post-treatment indicated no signs of cancer, suggesting that pembrolizumab may be a safe and effective option for advanced vulvar cancer where traditional treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature. Shields, LBE., Gordinier, ME.[2019]

In a study of 101 patients with advanced vulvar squamous cell carcinoma, pembrolizumab monotherapy showed an overall objective response rate of 10.9%, with some patients experiencing durable responses lasting up to 28 months.

The treatment was generally well tolerated, with 50.5% of patients experiencing treatment-related adverse events, and only 5% discontinuing treatment due to side effects, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab for patients with previously treated advanced vulvar squamous cell carcinoma: Results from the phase 2 KEYNOTE-158 study. Shapira-Frommer, R., Mileshkin, L., Manzyuk, L., et al.[2022]

In a phase I trial involving 21 patients with locally advanced cervical cancer, the maximum tolerated dose (MTD) of weekly paclitaxel in combination with cisplatin was determined to be 40 mg/m², indicating a safe dosage for further studies.

The combination of weekly paclitaxel and cisplatin alongside radiation therapy was feasible and showed an acceptable toxicity profile, with significant side effects like grade 3 proctitis and vaginitis occurring at higher doses of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximum tolerated dose and early response - results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix. Prasad, E., Viswanathan, PN., Rangad, VF., et al.[2015]

The maximum-tolerated dose (MTD) of paclitaxel when combined with cisplatin and pelvic radiotherapy for cervical cancer patients was determined to be 50 mg/m2 per week, with diarrhea identified as the main dose-limiting toxicity.

In a study of 18 patients, the combination treatment resulted in a high overall response rate of 92.3%, with 7 complete and 5 partial responses, indicating that this regimen could be an effective option for treating locally advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. Pignata, S., Frezza, P., Tramontana, S., et al.[2020]

A study involving 10 patients with advanced cervical cancer evaluated the safety of combining cisplatin with radiation therapy, finding that most adverse effects were mild (grade 2 or less), with nausea/vomiting being the most common issue.

Despite some cases of anemia being noted as a serious concern, the overall toxicity of the treatment was deemed acceptable, suggesting that larger studies can be conducted to further assess the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. Suggs, CL., Lee, JC., Lewis, GC., et al.[2013]

Weekly cisplatin chemotherapy at a dose of 25 mg/m² can be safely administered to a patient undergoing hemodialysis for cervical cancer, with treatment completed without interruptions and minimal acute toxicity.

The study found that while dialysis effectively eliminates platinum from the body, starting dialysis as soon as possible after cisplatin infusion is crucial to reduce the risk of myelotoxicity, which is linked to peak platinum levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent weekly cisplatin chemotherapy and radiotherapy in a haemodialysis patient with locally advanced cervix cancer. Zahra, MA., Taylor, A., Mould, G., et al.[2013]

In a phase II study involving 27 patients with locally advanced or recurrent cervical carcinoma, the combination of cisplatin and Taxol chemotherapy with radiotherapy resulted in a complete clinical response in all patients, indicating high efficacy of this treatment approach.

The treatment was generally well tolerated, although some patients experienced significant side effects such as grade 3-4 neutropenia and grade 3 anemia, suggesting that while effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent external and endocavitary radiation therapy in locally advanced or recurrent cervical cancer. Miglietta, L., Franzone, P., Centurioni, MG., et al.[2015]

This study presents the first case of a complete response to pembrolizumab combined with pelvic radiotherapy in a patient with chemotherapy-refractory stage IVB vaginal squamous cell carcinoma, highlighting a potential new treatment option for this rare cancer.

The case also reports a novel immune-related adverse event, wall-eyed bilateral internuclear ophthalmoplegia (WEBINO), associated with the use of pembrolizumab, emphasizing the need for awareness of such effects in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rare case of chemotherapy-refractory metastatic vaginal squamous cell carcinoma with complete response to concurrent pembrolizumab and radiotherapy- case report and literature review. Ansari, J., Eltigani Mohmmed, Y., Ghazal-Aswad, S., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

A phase 2 study of combined chemo-immunotherapy with cisplatin-pembrolizumab and radiation for unresectable vulvar squamous cell carcinoma. [2021]

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

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in vaginal and vulvar squamous cell carcinoma: a case series from a phase II basket trial. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature. [2019]

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

Efficacy and safety of pembrolizumab for patients with previously treated advanced vulvar squamous cell carcinoma: Results from the phase 2 KEYNOTE-158 study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Maximum tolerated dose and early response - results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. [2020]

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

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Concurrent weekly cisplatin chemotherapy and radiotherapy in a haemodialysis patient with locally advanced cervix cancer. [2013]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent external and endocavitary radiation therapy in locally advanced or recurrent cervical cancer. [2015]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Rare case of chemotherapy-refractory metastatic vaginal squamous cell carcinoma with complete response to concurrent pembrolizumab and radiotherapy- case report and literature review. [2021]