Erlotinib in Women With Squamous Cell Carcinoma of the Vulvar

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00476476
• Collaborator: Genentech, Inc. (Industry), Beth Israel Deaconess Medical Center (Other), Brigham and Women's Hospital (Other), Women and Infants Hospital of Rhode Island (Other)
• Enrollment: 41
• Locations: 4
• Arm: 1
• Duration (Months): 70
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma	Drug: Erlotinib	Phase 2

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%.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Tarceva (Erlotinib) in Women With Squamous Cell Carcinoma of the Vulvar
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Erlotinib 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). 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.

Drug: Erlotinib; Orally every day for about 4-6 weeks; Other Names: Tarceva

Outcome Measures

Primary Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	Women and Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Genentech, Inc.
• Beth Israel Deaconess Medical Center
• Brigham and Women's Hospital
• Women and Infants Hospital of Rhode Island

Investigators

• Principal Investigator: Neil S. Horowitz, MD, Dana-Farber Cancer Institute/Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Neil S. Horowitz, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00476476
• Other Study ID Numbers: 06-174
• First Posted: May 22, 2007
• Last Update Posted: May 7, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Neil S. Horowitz, MD, Principal Investigator, Dana-Farber Cancer Institute: Tarceva; erlotinib; squamous cell carcinoma of the vulvar
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	Patients enrolled from February 2007 through July 2011.

Arm/Group Title	Erlotinib-Cohort 1	Erlotinib-Cohort 2
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	17	24
Response Evaluable	17	23
COMPLETED	15	0
NOT COMPLETED	2	24

Baseline Characteristics

Arm/Group Title	Erlotinib-Cohort 1	Erlotinib-Cohort 2	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	17	24	41
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	75	71.5	73
Sex: Female, Male (Count of Participants)
Female	17 100%	24 100%	41 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	17 100%	24 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	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).

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of response evaluable patients.

Arm/Group Title	Erlotinib-Cohort 1	Erlotinib-Cohort 2
Arm/Group Description	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.	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.
Measure Participants	17	23
Number (90% Confidence Interval) [proportion of participants]	.35 2.1%	.22 0.9%

Adverse Events

Time Frame	Assessed from time of first dose, weekly during treatment and through 30 days post-treatment.
Adverse Event Reporting Description	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.
Arm/Group Title	Erlotinib
Arm/Group Description	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). 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.
All Cause Mortality
	Erlotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Erlotinib
	Affected / at Risk (%)	# Events
Total	19/41 (46.3%)
Blood and lymphatic system disorders
Hemoglobin	2/41 (4.9%)
Ear and labyrinth disorders
Hearing w/w-o audiogr in monitor prg	2/41 (4.9%)
Gastrointestinal disorders
Colitis	1/41 (2.4%)
Diarrhea w/o prior colostomy	7/41 (17.1%)
Nausea	3/41 (7.3%)
Vomiting	1/41 (2.4%)
General disorders
Fatigue	2/41 (4.9%)
Infections and infestations
Infection-other	1/41 (2.4%)
Investigations
Death - disease progression NOS	2/41 (4.9%)
Bilirubin	1/41 (2.4%)
Creatinine	1/41 (2.4%)
Metabolism and nutrition disorders
Anorexia	1/41 (2.4%)
Dehydration	3/41 (7.3%)
Hypercalcemia	1/41 (2.4%)
Hyperglycemia	1/41 (2.4%)
Hypophosphatemia	1/41 (2.4%)
Hypokalemia	3/41 (7.3%)
Hyponatremia	2/41 (4.9%)
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness	1/41 (2.4%)
Bone, pain	1/41 (2.4%)
Psychiatric disorders
Confusion	1/41 (2.4%)
Renal and urinary disorders
Renal failure	3/41 (7.3%)
Urinary retention	1/41 (2.4%)
Reproductive system and breast disorders
Perineum, pain	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/41 (2.4%)
Hypoxia	1/41 (2.4%)
Pneumothorax	1/41 (2.4%)
Pulmonary/Upper Respiratory-other	1/41 (2.4%)
Skin and subcutaneous tissue disorders
Rash/desquamation	1/41 (2.4%)
Rash: acne/acneiform	1/41 (2.4%)
Hand-foot reaction	1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Erlotinib
	Affected / at Risk (%)	# Events
Total	40/41 (97.6%)
Blood and lymphatic system disorders
Hemoglobin	8/41 (19.5%)
Hematologic-other	1/41 (2.4%)
Cardiac disorders
Sinus tachycardia	1/41 (2.4%)
Endocrine disorders
Endocrine-other	1/41 (2.4%)
Eye disorders
Dry eye syndrome	1/41 (2.4%)
Eyelid dysfunction	1/41 (2.4%)
Tearing	1/41 (2.4%)
Ocular-other	2/41 (4.9%)
Gastrointestinal disorders
Constipation	4/41 (9.8%)
Diarrhea w/o prior colostomy	23/41 (56.1%)
Dry mouth	3/41 (7.3%)
Flatulence	1/41 (2.4%)
Dyspepsia	1/41 (2.4%)
Muco/stomatitis by exam, oral cavity	1/41 (2.4%)
Nausea	6/41 (14.6%)
Vomiting	7/41 (17.1%)
GI-other	3/41 (7.3%)
Abdomen, pain	2/41 (4.9%)
Peritoneum, pain	1/41 (2.4%)
General disorders
Fatigue	23/41 (56.1%)
Fever w/o neutropenia	2/41 (4.9%)
Edema limb	7/41 (17.1%)
Pain-other	8/41 (19.5%)
Flu-like syndrome	1/41 (2.4%)
Infections and infestations
Infection w/ gr3-4 neut, anal/perianal	1/41 (2.4%)
Infection Gr0-2 neut, lung	1/41 (2.4%)
Infection Gr0-2 neut, oral cavity	1/41 (2.4%)
Infection Gr0-2 neut, urinary tract	3/41 (7.3%)
Infection w/ unk ANC urinary tract NOS	1/41 (2.4%)
Injury, poisoning and procedural complications
Chemoradiation dermatitis	1/41 (2.4%)
Investigations
Leukocytes	1/41 (2.4%)
Platelets	1/41 (2.4%)
Weight loss	3/41 (7.3%)
Alkaline phosphatase	3/41 (7.3%)
ALT, SGPT	2/41 (4.9%)
AST, SGOT	5/41 (12.2%)
Bilirubin	1/41 (2.4%)
Creatinine	5/41 (12.2%)
Metabolic/Laboratory-other	2/41 (4.9%)
Metabolism and nutrition disorders
Anorexia	11/41 (26.8%)
Dehydration	7/41 (17.1%)
Hypoalbuminemia	8/41 (19.5%)
Bicarbonate	1/41 (2.4%)
Hypercalcemia	1/41 (2.4%)
Hypocalcemia	3/41 (7.3%)
Hyperglycemia	4/41 (9.8%)
Hypermagnesemia	1/41 (2.4%)
Hypomagnesemia	7/41 (17.1%)
Hypophosphatemia	1/41 (2.4%)
Hyperkalemia	1/41 (2.4%)
Hypokalemia	4/41 (9.8%)
Hyponatremia	1/41 (2.4%)
Musculoskeletal and connective tissue disorders
Back, pain	2/41 (4.9%)
Buttock, pain	1/41 (2.4%)
Neck, pain	1/41 (2.4%)
Nervous system disorders
Taste disturbance	3/41 (7.3%)
Dizziness	1/41 (2.4%)
Head/headache	2/41 (4.9%)
Psychiatric disorders
Anxiety	2/41 (4.9%)
Depression	1/41 (2.4%)
Renal and urinary disorders
Incontinence urinary	1/41 (2.4%)
Urinary frequency/urgency	1/41 (2.4%)
Renal/GU-other	4/41 (9.8%)
Reproductive system and breast disorders
Vagina, hemorrhage	3/41 (7.3%)
Perineum, pain	4/41 (9.8%)
Vagina, pain	3/41 (7.3%)
Vaginal discharge (non-infectious	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Chylothorax	1/41 (2.4%)
Cough	6/41 (14.6%)
Dyspnea	3/41 (7.3%)
Pulmonary/Upper Respiratory-other	1/41 (2.4%)
Skin and subcutaneous tissue disorders
Erythema multiforme	1/41 (2.4%)
Skin breakdown/decubitus ulcer	1/41 (2.4%)
Dry skin	12/41 (29.3%)
Alopecia	6/41 (14.6%)
Hyperpigmentation	1/41 (2.4%)
Nail changes	1/41 (2.4%)
Pruritus/itching	2/41 (4.9%)
Rash/desquamation	5/41 (12.2%)
Rash: acne/acneiform	17/41 (41.5%)
Ulceration	1/41 (2.4%)
Skin-other	2/41 (4.9%)
Scalp, pain	1/41 (2.4%)
Vascular disorders
Hypertension	2/41 (4.9%)
Hemorrhage-other	3/41 (7.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.