A novel phase II clinical trial is investigating a triple combination approach for treating advanced vulvar squamous cell carcinoma, combining the standard chemotherapy agent cisplatin with the immunotherapy drug pembrolizumab and radiation therapy. The single-arm study targets women with unresectable, incompletely resected, recurrent, or metastatic disease.
Study Design and Patient Population
The trial is designed to enroll approximately 24 participants with histologically or cytologically confirmed unresectable, incompletely resected, recurrent, or metastatic squamous cell carcinoma of the vulva. Patients with unresectable disease are specifically defined as having T2 or T3 primary tumors (N0-3, M0) that are not amenable to surgical resection by standard radical vulvectomy.
Eligible participants must have measurable disease based on RECIST 1.1 criteria, with lesions in previously irradiated areas considered measurable if progression has been demonstrated. The study requires archival tumor tissue samples or newly obtained core or excisional biopsies from tumor lesions not previously irradiated, with formalin-fixed, paraffin-embedded tissue blocks preferred over slides.
Treatment Protocol and Duration
Participants will receive study treatment for up to 36 weeks, with follow-up extending to 3 years. The combination therapy integrates cisplatin as standard of care chemotherapy, pembrolizumab as an investigational immunotherapy agent, and radiation therapy as a standard intervention.
The radiation component requires patients to safely receive a minimum of 30 Gy in 10 fractions, with those unable to tolerate this regimen excluded from participation. Prior radiotherapy is acceptable provided the site being considered for study has not been previously irradiated, and re-irradiation to previously treated sites is not permitted.
Eligibility Criteria and Safety Requirements
The study maintains strict eligibility criteria to ensure patient safety and data integrity. Participants must be at least 18 years old with an ECOG performance status of 0 or 1. Adequate organ and marrow function is required, including absolute neutrophil count ≥1,500/μL, platelets ≥100,000/μL, and hemoglobin ≥9.0 g/dL without erythropoietin dependency or recent blood transfusions.
Renal function requirements include creatinine ≤1.5 times the upper limit of normal or calculated creatinine clearance ≥50 mL/min. Hepatic function must demonstrate total bilirubin ≤1.5 times upper limit of normal and AST/ALT ≤2.5 times upper limit of normal (≤5 times for patients with liver metastases).
Prior Therapy Restrictions
The trial allows participants with no prior therapy as well as those with recurrent disease who have received no more than two lines of cytotoxic therapy. Topical or hormonal therapies are not counted toward prior treatment lines. Prior immunotherapy is permitted provided treatment was not discontinued due to grade 2 or greater adverse events.
Participants must have recovered from all adverse events due to previous therapies to grade 1 or baseline. Those who received prior systemic anti-cancer therapy or investigational agents within 4 weeks of study treatment are excluded, as are those who received radiotherapy within 2 weeks of study initiation.
Exclusion Criteria and Safety Considerations
The study excludes participants with vulvar melanomas, sarcomas, extramammary Paget's disease, or basal cell carcinoma, focusing specifically on squamous cell carcinoma. Patients with active autoimmune disease requiring systemic treatment within the past 2 years are excluded, though replacement therapies such as thyroxine or insulin are permitted.
Additional exclusions include active CNS metastases, history of non-infectious pneumonitis requiring steroids, active infections requiring systemic therapy, and known history of Hepatitis B, Hepatitis C, tuberculosis, or HIV. Participants with other invasive malignancies within the last five years, except non-melanoma skin cancer, are also excluded.
Regulatory Status and Study Rationale
The FDA has approved cisplatin as a treatment option for vulvar squamous cell carcinoma, while pembrolizumab, though approved for other indications, remains investigational for this specific cancer type. The study hypothesis centers on whether combining these agents with radiation therapy can enhance immune system efficiency in targeting tumor cells and reduce recurrence rates.
The research addresses an unmet medical need in vulvar cancer, a rare gynecologic malignancy where treatment options for advanced disease remain limited. By combining immunotherapy with chemoradiation, investigators aim to improve outcomes for patients with this challenging diagnosis.
