Cisplatin+Pembrolizumab+RT in Vulvar Cancer

NCT04430699 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-109
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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)

Conditions

Vulvar Cancer; Vulvar Squamous Cell Carcinoma

Keywords

Vulvar Cancer; Vulvar Squamous Cell Carcinoma,; Immunotherapy; Radiation; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  To determine the Overall response rate (ORR) in patients undergoing combination therapy with pembrolizumab and cisplatin-sensitized external beam radiation therapy by RECIST 1.1 criteria. This sample size calculation is based on an ORR of greater than or equal to 60%. For recurrent metastatic disease, there are is no standard of care.The ORR estimation is informed by data showing an ORR of 40% in patients with advanced or recurrent metastatic vulvar cancer treated with platinum-based combination therapy. Single agent chemotherapy has an ORR of about 12% (5). Patients with primary disease who are not candidates for upfront surgery have a reported response rates from 55% to 64%.

  Up to 36 weeks

Secondary Outcomes (1)

• Recurrence Free Survival (RFS)-6 months

  6 months

Study Arms (1)

Pembrolizumab, Cisplatin and Radiation Therapy

EXPERIMENTAL

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.

Drug: Cisplatin; Drug: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Cisplatin DRUG

Participants will be given Cisplatin by intravenous infusion at a predetermined dose 1x weekly up to 8 weeks.

Also known as: Platinol, Platinol-AQ, CDDP

Pembrolizumab, Cisplatin and Radiation Therapy

Pembrolizumab DRUG

Participants will be given Pembrolizumab by intravenous infusion at a predetermined dose 1x every 3 weeks up to 36 weeks.

Also known as: Keytruda

Pembrolizumab, Cisplatin and Radiation Therapy

Radiation Therapy RADIATION

Standard of care radiation therapy 1x daily up to 8 weeks.

Pembrolizumab, Cisplatin and Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed unresectable, incompletely resected, recurrent, or metastatic squamous cell carcinoma of the vulva.Patients with unresectable disease are defined as T2 or T3 primary tumors (N0-3, M0) not amenable to surgical resection by standard radical vulvectomy.
• Participants must have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
• Prior therapy: Participants with no prior therapy are eligible and patients with recurrent disease must not have had more than two lines of cytotoxic therapy. Topical or hormonal therapy are not counted towards prior lines. Prior treatment with immunotherapy is allowed, provided treatment was not stopped for grade 2 or greater adverse events.
• Time from prior therapy:
• Systemic anti-neoplastic therapy: 5 half-lives or 4 weeks, whichever is shorter.
• Hormonal therapy is not considered anti-neoplastic therapy.
• Radiotherapy: Any prior irradiation is acceptable provided the site being considered for study has not been previously irradiated.
• Age ≥18 years. Because insufficient dosing or adverse event data are currently available on the use of pembrolizumab in combination with cisplatin-sensitized radiation therapy participants \<18 years of age, children are excluded. Vulva cancer is rare in the pediatric population
• ECOG performance status of 0 or 1.
• Participants must have adequate organ and marrow function as defined below (Table 1):
• Table 1: Adequate Organ Function Laboratory Values
• Hematological
• Absolute neutrophil count (ANC) ≥1500/μL
• Platelets ≥100 000/μL

You may not qualify if:

• Patients who in the opinion of the investigator cannot safely receive a minimum of 30 Gy in 10 fractions are not eligible for the trial.
• Participants who have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to first dose of study treatment. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. Re-irradiation to a previously treated site will not be permitted.
• Participants who have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Participants with vulvar melanomas, sarcomas, extramammary Paget's disease, or basal cell carcinoma
• Participants with a history of gastrointestinal or colovesicular fistulae
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Patients with a history of other invasive malignancies, with the exception of nonmelanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
• Participants with uncontrolled intercurrent illness.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Yeku O, Russo AL, Lee H, Spriggs D. A phase 2 study of combined chemo-immunotherapy with cisplatin-pembrolizumab and radiation for unresectable vulvar squamous cell carcinoma. J Transl Med. 2020 Sep 14;18(1):350. doi: 10.1186/s12967-020-02523-5.

  PMID: 32928237 BACKGROUND

MeSH Terms

Conditions

Vulvar Neoplasms

Interventions

Cisplatin; pembrolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Vulvar Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Oladapo Yeku, MD, PHD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 10, 2020
• First Posted: June 12, 2020
• Study Start: July 29, 2020
• Primary Completion: April 30, 2026
• Study Completion (Estimated): January 30, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)