Cancer
Conditions
Keywords
Phase II, Erlotinib, Radiotherapy, Squamous Cell Carcinomas, Cutaneous, Stage III
Brief summary
This is a phase II study designed to study the effectiveness of combined radiotherapy and erlotinib in the postoperative setting for patients with cutaneous SCC that are at high risk for recurrence. Participants enrolled in the study will be evaluated by a head and neck surgeon, and a radiation oncologist. Whenever possible, a preoperative biopsy will be performed after participant enrollment in the study for histological confirmation and for molecular correlates. Participants enrolled prior to surgical resection will begin erlotinib at 150 mg by mouth (PO) every day (QD) (14 tablets) to be taken 14 days prior to surgical resection. Following planned surgical resection, the participant will begin Erlotinib therapy and radiotherapy at the same time and within 4-8 weeks of the surgical resection.
Detailed description
This is a single-institution, open-label, non-randomized phase II trial of erlotinib administered concomitantly with radiation therapy following surgical resection of gross disease. A total of 45 patients with previously unirradiated, high-risk cutaneous SCC requiring post-operative radiotherapy will be enrolled to assess the primary endpoints of time to recurrence and disease free survival. Pretreatment biopsies will be required to confirm the histological diagnosis of SCC. Four to six weeks after surgical resection, patients will begin erlotinib (150 mg po qd) beginning the first day of radiotherapy. Patients will receive 5040 cGy beginning on day 1 of therapy in standard fractionations. Patients will be followed to evaluate for toxicity based on NCI common toxicity criteria (v3.0). Patients will be followed on protocol for a minimum of 2 years with regularly scheduled CT scans, clinical evaluations, and laboratory work. Patients with residual or recurrent cancer will be taken off protocol for salvage therapy. As a secondary objective, molecular response of tumors to erlotinib monotherapy will be determined. When possible, participants will be enrolled and treated for 14 days with erlotinib prior to surgical resection. The pretreatment biopsy specimen (control) will then be compared to tissue acquired during the surgical resection after 14 days of erlotinib (experimental group).
Interventions
DRUGErlotinib
Erlotinib therapy for 2 weeks (150 mg po qd)(for those who are enrolled before surgery is done), surgery/biopsy up to 8 weeks recovery, radiation/Erlotinib therapy for 6 weeks (150mg po qd).
Sponsors
Genentech, Inc.
OSI Pharmaceuticals
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven primary or recurrent squamous cell carcinoma arising from the lip or skin of the face, ear, scalp or neck. * Participants must meet one of the four criteria: * 1\. T4 cutaneous SCC as determined by physical exam, imaging studies, prior resections or biopsy. T4 disease is defined as tumor that invades deep extradermal structures such as cartilage, skeletal muscle (e.g., muscles of facial expression), parotid gland or bone.Patients with a T2 or greater squamous cell carcinoma of the lower lip who will require post operative radiation will be allowed. * 2\. Histologically proven regional lymph node involvement (N1 disease). Fine needle aspiration or biopsy can be used to demonstrate the presence of lymphatic spread. * 3\. Histologically proven parotid gland metastasis. Fine needle aspiration or biopsy can be used to demonstrate the presence of regional spread. Includes delayed regional metastasis; primary scalp or other skin lesion treated within 36 months that would drain into the involved parotid. * 4\. Patients who following surgical resection of the primary are found to have histologically positive lymph nodes (N1). Includes delayed regional metastasis; primary lip or cutaneous lesion treated within 36 months that would drain into the involved nodal basin. * Age \> 19 years * Tumors must be considered surgically resectable.(Patients may be enrolled after surgery is completed as long as Erlotinib therapy and concurrent radiation is started within 8 weeks of surgical resection.) * Required laboratory data obtained prior to beginning treatment: WBC \> 1,500/ml; Platelets \> 90,000; serum creatinine ≤ 2.0 mg/dl * The patient may have had a prior non-cutaneous malignancy, but must be two years from treatment. * Performance status of ≤ 2 (ECOG scale) and life expectancy ≥ 12 months. * The patients must agree to use effective contraception if there is the potential for procreativity. Contraception must be conducted for at least 3 months following the study. * Patients must sign informed consent
Exclusion criteria
* The patient has received prior radiation therapy to the head and neck. * The patient is pregnant or lactating * Patients with a prior history of head and neck mucosal cancers. * Psychological condition that renders the patient unable to understand the informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicities Associated With Combined Radiotherapy and Erlotinib Treatments. | 2 years | Number of gradeable toxicities (via CTCAE manual) experienced by patients on this protocol--number of events |
| Median Time to Cancer Recurrence | 2 years | Per protocol, patients were followed every 3 months for recurrent disease by physical exam and imaging (MRI/CT). Recurrence, in most cases, is detected during routine history/physical exam. If disease was detected during follow-up, every attempt was made to obtain pathological confirmation of recurrence. |
| Number of Patients With Recurrence at 2 Years | 2 years | Rate of recurrence at 2 years. |
Countries
United States
Participant flow
Recruitment details
Period of recruitment was December 2006 to June 2009. Patients were screened from radiation and head/neck clinics at UAB Hospital.
Pre-assignment details
Single Arm study
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Erlotinib therapy for 2 weeks (150 mg once per day)(for those who are enrolled before surgery is done), surgery/biopsy up to 8 weeks recovery, radiation/Erlotinib therapy for 6 weeks (150mg once per day). | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Erlotinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 68 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 5 / 15 |
Outcome results
Primary
Median Time to Cancer Recurrence
Per protocol, patients were followed every 3 months for recurrent disease by physical exam and imaging (MRI/CT). Recurrence, in most cases, is detected during routine history/physical exam. If disease was detected during follow-up, every attempt was made to obtain pathological confirmation of recurrence.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Median Time to Cancer Recurrence | 10.5 months |
Primary
Number of Patients With Recurrence at 2 Years
Rate of recurrence at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Number of Patients With Recurrence at 2 Years | 4 participants |
Primary
Toxicities Associated With Combined Radiotherapy and Erlotinib Treatments.
Number of gradeable toxicities (via CTCAE manual) experienced by patients on this protocol--number of events
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Toxicities Associated With Combined Radiotherapy and Erlotinib Treatments. | Dermatitis | 15 number of adverse events |
| Erlotinib | Toxicities Associated With Combined Radiotherapy and Erlotinib Treatments. | Radiation Dermatitis | 14 number of adverse events |
| Erlotinib | Toxicities Associated With Combined Radiotherapy and Erlotinib Treatments. | Tarceva Dermatitis | 12 number of adverse events |
| Erlotinib | Toxicities Associated With Combined Radiotherapy and Erlotinib Treatments. | Mucositis | 13 number of adverse events |
| Erlotinib | Toxicities Associated With Combined Radiotherapy and Erlotinib Treatments. | Esophagitis | 11 number of adverse events |
| Erlotinib | Toxicities Associated With Combined Radiotherapy and Erlotinib Treatments. | Nausea/Vomitting | 10 number of adverse events |