Phase II Study of Skin Toxicity Dosing of IRESSA (Gefitinib) in Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the activity (response rate and rate of stable disease) of Iressa administered as a single agent escalated to a dose that produces grade 2 skin toxicity in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Detailed Description
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This open-label, multi-institution, phase II study evaluated the activity of gefitinib at individually escalated doses up to 750mg to achieve the skin toxicity grade greater than or equal to 2. Patients were started on gefitinib 250mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose was escalated to 500 mg daily and again to 750 mg daily on next evaluation until grade 2 or greater skin toxicity was developed. The protocol was later amended because of the reported lower efficacy of the 250 mg dose and patients were then started at 500 mg per day. There was no further dose escalation beyond 750 mg per day irrespective of the response or grade of skin toxicity. Therapy was discontinued upon disease progression, unacceptable toxicity, death or patient's withdrawal of consent. Dose interruptions were used as the first approach to managing the toxicity of the patients who experienced grade 3-4 non-hematological toxicities. Gefitinib was interrupted for up to a maximum of 14 days until the toxicities dropped to grade 1 or less. Adherence to therapy was monitored using drug diaries that were collected at each physician visit and assessed against pill counts.

Official Title
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Phase II Study of Skin Toxicity Dosing of IRESSA (Gefitinib) as Monotherapy in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: Gefitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: squamous cell carcinoma of the head and neck Tumour site that is amenable to biopsy. Patients can refuse biopsy and still participate in the study but all patients must have disease that can be biopsied Aged 18 years or older Prior epidermal growth factor receptor (EGFR) based therapy is allowed if greater than 4 months have elapsed since last dose of that agent and study entry No chemotherapy or irradiation within the 28-day period preceding entry to the study. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Ability to understand and the willingness to sign a written informed consent document. Normal organ and marrow function Exclusion Criteria: Known severe hypersensitivity to Iressa or any of the excipients of this product Other co-existing malignancies or malignancies diagnosed within the last 3 years with the exception of basal cell carcinoma or cervical cancer in situ Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy (except alopecia). Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial Pregnancy or breast feeding women Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment Any evidence of clinically active interstitial lung disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gefitinib<br>Patients were started on gefitinib 250 mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose 250-mg oral dose-escalating dose; each patient received treatment at the dose that produced grade 2 skin toxicity until disease progression or withdrawal. | Drug: Gefitinib<br>* Patients were started on gefitinib 250 mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose 250-mg oral dose-escalating dose; each patient received treatment at the dose that produced grade 2 skin toxicity until disease progression or withdrawal.<br>* Other names: IRESSA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response (CR or PR), Stable Disease (SD), and Progressive Disease (PD) Rates | The proportion of subjects that responded [complete (CR) or partial response (PR)], had stable disease (SD), or progressive disease (PD) as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter (LD) since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression-free Survival Time | Progression-free survival (PFS) is the number of months during and after Gefitinib treatment during which the cancer did not get worse (progress) as defined by Response Evaluation Criteria In Solid Tumors (RECIST). Progressive disease is associated with at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. All patients developed progressive disease or died during the 9-month observation period. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, squamous cell, carcinoma, head, neck