Squamous Cell Carcinoma
Conditions
Keywords
Tarceva, erlotinib, squamous cell carcinoma of the vulvar
Brief summary
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.
Detailed description
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%.
Interventions
DRUGErlotinib
Orally every day for about 4-6 weeks
Sponsors
Genentech, Inc.
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Women and Infants Hospital of Rhode Island
Dana-Farber Cancer Institute
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Assessed prior to definitive surgery or chemoradiation therapy (cohort 1 pts) or after 2 cycles of therapy (cohort 2 pts). | Response is defined as achieving complete or partial response.Complete response (CR) for both cohorts was defined as resolution of all identified tumor masses on the vulva or disappearance of all target and non-target lesions with no evidence of new lesions documented by two disease assessments at least 4 weeks apart. For cohort 1 pts, a partial response (PR) was defined as a 30% reduction in the product of all diameters of the vulva tumor/tumors compared to baseline measurements. For cohort 2 pts, PR defined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was at least a 30% decrease in the sum of the longest diameter (LD) of all target measurable lesions (baseline sum LD reference). |
Countries
United States
Participant flow
Recruitment details
Patients enrolled from February 2007 through July 2011.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib-Cohort 1 Patients rcvd oral erlotinib 150 mg/day. Cohort 1 pts would have at least 28 days and no more than 42 days of therapy in advance of definitive therapy (surgery or chemoradiation). Two potential dose reductions were prescribed to 100 and 50 mg/day. | 17 |
| Erlotinib-Cohort 2 Patients rcvd oral erlotinib 150 mg/day. Cohort 2 pts continued on therapy (28 days per cycle) until disease progression, unacceptable toxicity or withdrawal of consent. Two potential dose reductions were prescribed to 100 and 50 mg/day. | 24 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 7 |
| Overall Study | Progressive Disease | 0 | 17 |
Baseline characteristics
| Characteristic | Erlotinib-Cohort 1 | Erlotinib-Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 75 years | 71.5 years | 73 years |
| Region of Enrollment United States | 17 participants | 24 participants | 41 participants |
| Sex: Female, Male Female | 17 Participants | 24 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 41 |
| serious Total, serious adverse events | 19 / 41 |
Outcome results
Primary
Response Rate
Response is defined as achieving complete or partial response.Complete response (CR) for both cohorts was defined as resolution of all identified tumor masses on the vulva or disappearance of all target and non-target lesions with no evidence of new lesions documented by two disease assessments at least 4 weeks apart. For cohort 1 pts, a partial response (PR) was defined as a 30% reduction in the product of all diameters of the vulva tumor/tumors compared to baseline measurements. For cohort 2 pts, PR defined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was at least a 30% decrease in the sum of the longest diameter (LD) of all target measurable lesions (baseline sum LD reference).
Time frame: Assessed prior to definitive surgery or chemoradiation therapy (cohort 1 pts) or after 2 cycles of therapy (cohort 2 pts).
Population: The analysis dataset is comprised of response evaluable patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib-Cohort 1 | Response Rate | .35 proportion of participants |
| Erlotinib-Cohort 2 | Response Rate | .22 proportion of participants |