Stage IIIA Vulvar Cancer AJCC v7, Stage IIIB Vulvar Cancer AJCC v7, Stage IIIC Vulvar Cancer AJCC v7, Stage III Vulvar Cancer AJCC v7, Stage IVA Vulvar Cancer AJCC v7, Vulvar Squamous Cell Carcinoma
Conditions
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.
Interventions
DRUGCisplatin
Given IV
DRUGGemcitabine Hydrochloride
Given IV
RADIATIONIntensity-Modulated Radiation Therapy
Undergo IMRT
PROCEDURETherapeutic Conventional Surgery
Undergo local core biopsy or surgical excision
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
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
United States
Participant flow
Recruitment details
GOG-0279 was activated on 07/02/2012 and closed to accrual on February 20, 2020.
Participants by arm
| Arm | Count |
|---|---|
| GEM+CIS+IMRT Gemcitabine 50 mg/m2 and Cisplatin 40mg/m2 administered weekly throughout IMRT radiation therapy. Gemcitabine will be infused prior to cisplatin and given over approximately 30 minutes while the cisplatin will be delivered over approximately 60 minutes. | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Inadequate Pathology | 1 |
| Overall Study | Never Treated | 3 |
Baseline characteristics
| Characteristic | GEM+CIS+IMRT |
|---|---|
| Age, Customized 20 - 29 years | 1 Participants |
| Age, Customized 30 - 39 years | 0 Participants |
| Age, Customized 40 - 49 years | 6 Participants |
| Age, Customized 50 - 59 years | 23 Participants |
| Age, Customized 60 - 69 years | 10 Participants |
| Age, Customized 70 - 79 years | 8 Participants |
| Age, Customized >= 80 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 50 Participants |
| Sex: Female, Male Female | 53 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 53 |
| other Total, other adverse events | 53 / 53 |
| serious Total, serious adverse events | 24 / 53 |
Outcome results
Primary
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.
Time frame: 6 -8 weeks after completion of chemo-radiation
Population: Eligible and treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GEM+CIS+IMRT | Complete Pathologic Response | 73.6 percentage of participants |
Secondary
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.
Time frame: 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.
Population: Eligible and Treated
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Leukopenia | 27 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Thrombocytopenia | 20 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Neutropenia | 20 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Anemia | 20 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Other Investigations | 7 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Other blood and lymphatic disorders | 8 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Cardiac disorders | 2 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Gastrointestinal disorders | 10 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | General disorders and administration site conditions | 5 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Infections and infestations | 5 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Injury, poisoning and procedural complications | 20 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Metabolism and nutrition disorders | 19 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Musculoskeletal and connective tissue disorders | 2 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Peripheral sensory neuropathy | 1 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Other nervous system disorders | 2 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Renal and urinary disorders | 1 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Reproductive system and breast disorders | 7 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Skin and subcutaneous tissue disorders | 4 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Surgical and medical procedures | 1 Participants |
| GEM+CIS+IMRT | Adverse Events (Grade 3 or Higher) During Treatment Period | Vascular disorders | 5 Participants |
Secondary
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.
Time frame: 6-8 weeks after completion of chemo-radiation
Population: Eligible and Treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GEM+CIS+IMRT | Complete Clinical Response | 71.7 percentage of participants |
Secondary
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
Time frame: 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
Population: Eligible and treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GEM+CIS+IMRT | Progression-free Survival (PFS) | 75 percentage of participants |