Radiation Therapy, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Locally Advanced Squamous Cell Cancer of the Vulva

Study Overview
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Brief Summary
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This phase II trial studies how well radiation therapy works when given with gemcitabine hydrochloride and cisplatin work in treating patients with squamous cell cancer of the vulva that has spread from where it started to nearby tissue or lymph nodes. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving radiation therapy together with gemcitabine hydrochloride and cisplatin may kill more tumor cells.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the efficacy of cisplatin, gemcitabine (gemcitabine hydrochloride), and intensity-modulated radiation therapy (IMRT) in achieving a complete pathologic response when used for the primary treatment of locally-advanced squamous cell carcinoma of the vulva. SECONDARY OBJECTIVES: I. To determine the efficacy of cisplatin, gemcitabine, and IMRT in achieving a complete clinical response when used for the primary treatment of locally-advanced squamous cell carcinoma of the vulva. II. To determine the vulvar progression-free survival and groin progression-free survival in women treated with cisplatin, gemcitabine and IMRT for locally advanced vulvar carcinoma. III. To determine the toxicity and surgical morbidity of the combined modality approach of cisplatin, gemcitabine and IMRT followed by reduced-scope surgery for the treatment of locally-advanced vulvar carcinoma. OUTLINE: Patients undergo IMRT 5 days a week for 6 weeks. Patients also receive gemcitabine hydrochloride intravenously (IV) over 30 minutes and cisplatin IV over 60 minutes weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Within 6-8 weeks after completion of chemoradiation patients undergo local core biopsy to confirm response or surgical excision of gross residual disease in the vulva and/or inguinal-femoral lymph nodes. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Official Title
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A Phase II Trial Evaluating Cisplatin (NSC #119875) and Gemcitabine (NSC #613327) Concurrent With Intensity-Modulated Radiation Therapy (IMRT) in the Treatment of Locally Advanced Squamous Cell Carcinoma of the Vulva (NCT #01595061)

Conditions
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Vulvar Squamous Cell Carcinoma, Stage III Vulvar Cancer AJCC v7, Stage IIIA Vulvar Cancer AJCC v7, Stage IIIB Vulvar Cancer AJCC v7, Stage IIIC Vulvar Cancer AJCC v7, Stage IVA Vulvar Cancer AJCC v7

Intervention / Treatment
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* Drug: Cisplatin
* Drug: Gemcitabine Hydrochloride
* Radiation: Intensity-Modulated Radiation Therapy
* Procedure: Therapeutic Conventional Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advanced, previously untreated squamous cell carcinoma of the vulva Patients with T2 or T3 primary tumors (N0-3, M0) not amenable to surgical resection by standard radical vulvectomy Absolute neutrophil count (ANC) >= 1,500/mcl Platelets >= 100,000/mcl Creatinine =< 1.5 times institutional upper limit of normal (ULN) OR calculated creatinine clearance >= 60 mL/min Bilirubin =< 1.5 x ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN Alkaline phosphatase =< 3 x ULN Patients judged capable of tolerating a radical course of chemoradiation therapy Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population Patients must have signed an approved informed consent and authorization permitting release of personal health information Patients with a GOG performance status of 0, 1, or 2 Exclusion Criteria: Patients with recurrent carcinoma of the vulva regardless of previous treatment Patients who have received prior pelvic radiation or cytotoxic chemotherapy Patients with vulvar melanomas or sarcomas Patients with circumstances that will not permit completion of the study or the required follow-up Patients with evidence of active septicemia, severe infection, gastrointestinal bleeding or severe gastrointestinal symptoms requiring medical or surgical therapy Patients with a history of other invasive malignancies, with the exception of non-melanoma 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (IMRT, gemcitabine, cisplatin, surgery)<br>Patients undergo IMRT 5 days a week for 6 weeks. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 60 minutes weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Within 6-8 weeks after completion of chemoradiation patients undergo local core biopsy to confirm response or surgical excision of gross residual disease in the vulva and/or inguinal-femoral lymph nodes. | Drug: Cisplatin<br>* Given IV<br>* Other names: Platosin;Drug: Gemcitabine Hydrochloride<br>* Given IV<br>* Other names: LY188011;Radiation: Intensity-Modulated Radiation Therapy<br>* Undergo IMRT<br>* Other names: Radiation, Intensity-Modulated Radiotherapy;Procedure: Therapeutic Conventional Surgery<br>* Undergo local core biopsy or surgical excision<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Pathologic Response | Percentage of participants with complete pathologic response. Complete pathologic response is defined as negative local core biopsy or FNA specimens following primary chemo-radiation therapy. | 6 -8 weeks after completion of chemo-radiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Clinical Response | Percentage of participants with complete clinical response. Complete clinical response is defined as no clinical/radiographic evidence of primary disease (vulva or groin) following primary chemo-radiation therapy. | 6-8 weeks after completion of chemo-radiation | 
| Adverse Events (Grade 3 or Higher) During Treatment Period | Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0. | During treatment period and up to 30 days after stopping the study treatment. The median for duration of study treatment was 2.1 months with a range from 1.2 months to 4.6 months. | 
| Progression-free Survival (PFS) | Estimate for probability of progression free survival by Kaplan-Meier method, where progression-free survival is defined as the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. PFS is censored in patients who are alive and have not progressed. Progression is assessed by RECIST 1.1 | From study entry to disease progression, death or date of last contact, whichever occurs first. The median for observed PFS was 26.2 month with a range from 1.5 months to 82.4 months |