Stage III Vulvar Cancer, Stage IVB Vulvar Cancer, Vulvar Squamous Cell Carcinoma
Conditions
Brief summary
This phase II trial is studying how well giving radiation therapy together with cisplatin followed by surgery works in treating patients with locally advanced cancer of the vulva. Drugs used in chemotherapy such as cisplatin use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving chemotherapy with radiation therapy before surgery may shrink the tumor so it can be removed during surgery.
Detailed description
OBJECTIVES: I. Determine the efficacy of radiotherapy and cisplatin, in terms of achieving a complete clinical and pathological response, in patients with locally advanced squamous cell carcinoma of the vulva that is not amenable to standard radical vulvectomy. II. Determine the toxicity of this regimen followed by surgery in these patients. OUTLINE: This is a multicenter study. Patients undergo radiotherapy daily on days 1-5 and receive concurrent cisplatin IV over 30 minutes on day 1. Treatment repeats weekly for approximately 6.5 weeks (a total of 32 fractions of radiotherapy) in the absence of unacceptable toxicity. Six to eight weeks after the completion of chemoradiotherapy, patients with a complete clinical response may undergo incisional biopsy of the primary tumor and bilateral inguinal/femoral nodes (if the groin nodes were initially unresectable). Patients with microscopic or gross resectable residual disease may then undergo radical resection of the residual tumor. Patients with unresectable disease after the completion of chemoradiotherapy receive additional radiotherapy with 1-2 courses of concurrent cisplatin. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Interventions
RADIATION3-Dimensional Conformal Radiation Therapy
DRUGCisplatin
Given IV
PROCEDUREConventional Surgery
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Diagnosis of locally advanced squamous cell carcinoma of the vulva * T3 or T4 (N0-3, M0) * Not amenable to surgical resection by standard radical vulvectomy * Previously untreated disease * No recurrent disease * No vulvar melanoma or sarcoma * Performance status - GOG 0-3 * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Bilirubin no greater than 1.5 times normal * Alkaline phosphatase no greater than 3 times normal * SGOT no greater than 3 times normal * Creatinine no greater than 2.0 mg/dL * No gastrointestinal bleeding * No severe gastrointestinal symptoms * Capable of tolerating a radical course of chemoradiotherapy * No septicemia * No severe infection * No other invasive malignancy within the past 5 years except nonmelanoma skin cancer * No circumstance that would preclude study completion or follow-up * No prior cytotoxic chemotherapy * No prior pelvic radiotherapy * No concurrent boost brachytherapy * No prior anticancer therapy that would contraindicate study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Clinical and Pathologic Response | Seven weeks after initiating treatment for clinical response and up to fifteen weeks for assessment of pathologic response. | Complete clinical and pathologic response is defined as the disappearance of all gross tumor during chemoradiation with no residual tumor present in the surgical specimen. |
| Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Assessed every cycle while on treatment, 30 days after the last cycle of treatment. Up to eleven weeks from the start of study treatment | Number of participants with a maximum grade of 3 or higher during the treatment period. Adverse events are graded and categorized using Common Terminology Criteria for Adverse Events Version 2.0 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cisplatin + Radiation, Then Surgery Radiation therapy to the vulva, inguinal-femoral, and lower pelvic lymph nodes by AP-PA fields (180 cGy/daily fraction X 5 days, repeated weekly to a total of 32 fractions- total dose 5760 Gy). Concurrent cisplatin (40 mg/m2) chemotherapy administered weekly throughout radiation therapy. Six to eight weeks following the completion of chemoradiation - surgical excision of gross residual disease in the vulva and/or inguinal-femoral lymph nodes (if the inguinal-femoral nodes were considered unresectable prior to chemoradiation). | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible-improper pre-protocol treatm | 1 |
| Overall Study | Ineligible-Inadequate Pathology | 2 |
Baseline characteristics
| Characteristic | Cisplatin + Radiation, Then Surgery |
|---|---|
| Age, Customized Age of participants 40-49 years | 9 Participants |
| Age, Customized Age of participants <40 years | 5 Participants |
| Age, Customized Age of participants 50-59 years | 17 Participants |
| Age, Customized Age of participants 60-69 years | 13 Participants |
| Age, Customized Age of participants >=70 years | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 54 Participants |
| Sex: Female, Male Female | 58 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 58 / 58 |
| serious Total, serious adverse events | 17 / 58 |
Outcome results
Primary
Complete Clinical and Pathologic Response
Complete clinical and pathologic response is defined as the disappearance of all gross tumor during chemoradiation with no residual tumor present in the surgical specimen.
Time frame: Seven weeks after initiating treatment for clinical response and up to fifteen weeks for assessment of pathologic response.
Population: Eligible and treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cisplatin + Radiation, Then Surgery | Complete Clinical and Pathologic Response | 50 Percentage of Participants |
Primary
Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period
Number of participants with a maximum grade of 3 or higher during the treatment period. Adverse events are graded and categorized using Common Terminology Criteria for Adverse Events Version 2.0
Time frame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment. Up to eleven weeks from the start of study treatment
Population: Eligible and treated patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Leukopenia | 18 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Anemia | 4 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Thrombocytopenia | 3 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Neutropenia | 11 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Other Hematologic | 13 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Constitutional | 5 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Cardiovascular | 4 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Dermatologic | 17 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Gastrointestinal | 13 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Genitourinary/Renal | 3 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Pulmonary | 1 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Pain | 10 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Sexual/reproductive | 1 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | hemorrhage | 1 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Infection | 8 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Metabolic | 10 Participants |
| Cisplatin + Radiation, Then Surgery | Treatment-Related Adverse Effects (Grade 3 or Higher) During Study Treatment Period | Other Neurologic | 2 Participants |