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

Phase 2

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

Interventions: Drug: Cisplatin
Drug: Gemcitabine Hydrochloride
Radiation: Intensity-Modulated Radiation Therapy
Procedure: Therapeutic Conventional Surgery

Registration Number: NCT01595061

Lead Sponsor: Gynecologic Oncology Group

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: UNKNOWN

Sex: Female

Target Recruitment: 57

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (IMRT, gemcitabine, cisplatin, surgery)	Intensity-Modulated Radiation Therapy	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.
Treatment (IMRT, gemcitabine, cisplatin, surgery)	Therapeutic Conventional Surgery	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.
Treatment (IMRT, gemcitabine, cisplatin, surgery)	Gemcitabine Hydrochloride	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.
Treatment (IMRT, gemcitabine, cisplatin, surgery)	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Complete Pathologic Response	6 -8 weeks after completion of chemo-radiation	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.

Secondary Outcome Measures

Name	Time	Method
Adverse Events (Grade 3 or Higher) During Treatment Period	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.	Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Progression-free Survival (PFS)	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	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
Complete Clinical Response	6-8 weeks after completion of chemo-radiation	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.

Trial Locations

Locations (193): University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
Anchorage Associates in Radiation Medicine
🇺🇸
Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸
Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸
Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸
Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸
Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸
Burbank, California, United States
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University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States