A Phase 2 Study of Combined Chemo-immunotherapy With Cisplatin-pembrolizumab and Radiation for Unresectable Vulvar Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Cisplatin
- Conditions
- Vulvar Cancer
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Overall response rate (ORR)
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
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)
Detailed Description
This is a single-arm phase 2 clinical trial involving women with unresectable, incompletely resected, recurrent, or metastatic vulva squamous cell carcinoma. This study combines cisplatin, pembrolizumab, and radiation therapy to see if this combination further increases participants' immune system's efficiency in killing their tumor, and if the combination decreases the chances of participants' cancer coming back. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. This research study involves the following: * Cisplatin (standard of care drug) * Pembrolizumab (investigational drug) * Radiation Therapy (standard of care intervention) Participants will receive study treatment for up to 36 weeks and will be followed for up to 3 years. It is expected that about 24 people will take part in this research study. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has approved cisplatin as a treatment option for vulva squamous cell carcinoma. The FDA has not approved pembrolizumab for vulva squamous cell carcinoma, but it has been approved for other uses. Cisplatin is a chemotherapy drug and will be given to participants per standard of care. Radiation therapy will be given to you per standard of care. Pembrolizumab is a drug that may target participants immune systems to increase its efficiency in targeting and killing illnesses and diseases, such as unresectable vulvar squamous cell carcinoma.
Investigators
Oladapo O. Yeku,M.D.,Ph.D.
Principal Investigator
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •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.
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Pembrolizumab, Cisplatin and Radiation Therapy
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.
Intervention: Cisplatin
Pembrolizumab, Cisplatin and Radiation Therapy
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.
Intervention: Pembrolizumab
Pembrolizumab, Cisplatin and Radiation Therapy
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.
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Overall response rate (ORR)
Time Frame: Up to 36 weeks
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%.
Secondary Outcomes
- Recurrence Free Survival (RFS)-6 months(6 months)