In this research study we are looking to see how vulvar cancer responds to erlotinib therapy. Two distinct patient populations are targeted: women with locally advanced measurable squamous cell carcinoma of the vulva, primary or recurrent, who are candidates for definitive treatment with surgery or chemoradiation (Cohort 1) and women with radiographically measurable distant metastatic cancer either at time of presentation or with recurrence (Cohort 2). Another goal of this study is to learn more about the proteins and genes present in vulvar cancer and how they may affect response to erlotinib. Erlotinib treats cancer by preventing cancer cells from growing and multiplying. It does this by blocking certain proteins that are on the surface of some types of cancer cells. Laboratory tests show that vulvar cancer cells have high levels of these proteins.

OBJECTIVES:

Primary

• To determine the clinical efficacy of erlotinib in reducing the size of vulvar squamous cell cancer and /or metastatic lesions.

Secondary

• To determine the safety and tolerability of oral erlotinib.
• To evaluate apoptosis and assess the Ki67, phospho-EGFR, EGFR mutation and EGFR amplification status of the vulvar cancer prior to and after therapy and correlate observed changes with response to therapy.
• To evaluate the impact of medical treatment on the subsequent surgery for vulvar cancer when surgery is chosen as the definitive therapy.

STATISTICAL DESIGN:

This study used a two-stage design to evaluate efficacy of erlotinib based on response determined prior to definitive surgery or chemoradiation (cohort 1) or after every 2 cycles of erlotinib (cohort 2). The null and alternative response rates defined as achieving partial response (PR) or better were 3.5% and 15%. If 1 or more patients enrolled in stage one (n=17 patients) achieved PR or better than accrual would proceed to stage two (n=24 patients). There was 0.55 probability of stopping the trial at stage one if the true OR rate was 3.5%. If 3 or fewer responses were observed by the end of stage two, erlotinib would be deemed ineffective. The significance level of the study design was 0.0495 with a power of 85% to rule out a poor response rate of less than 3.5%.

Inclusion Criteria:

• Histologically confirmed measurable squamous cell carcinoma of the vulvar with an assessable lesion on the vulva or measurable metastatic disease. Tumors may be primary or recurrent. Patients must have plans for surgery or definitive treatment with chemotherapy +/-radiation unless they have measurable metastatic disease.
• 18 years of age or older
• No concurrent chemotherapy or radiotherapy
• NO previous chemotherapy or radiotherapy within the preceding 1 month
• ECOG performance status of 0-1

Exclusion Criteria:

• Known hypersensitivity reaction to erlotinib
• Other coexisting malignancies diagnosed within the last 5 years, with the exception of basal cell carcinoma
• Treatment with a non-FDA approved or investigational drug within 30 days
• Persistent toxicities (grade 2 or above) from previous treatment, expect alopecia or lymphedema
• Serum creatinine level greater than CTC grade 2
• Pregnancy or breast feeding
• Severe or uncontrolled systemic disease
• Significant clinical disorder or laboratory finding that makes it potentially unsafe for the subject to participate

The analysis population is comprised of all enrolled patients.

Assessed from time of first dose, weekly during treatment and through 30 days post-treatment.

Serious AEs were defined as treatment-related events of grade 3 or higher per CTCAEv3.

Other AEs were defined as treatment-related events of grades 1 or 2 per CTCAEv3.