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

NCT ID: NCT00519077

Last Updated: 2016-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2013-05-31

Brief Summary

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

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.

Conditions

Head and Neck Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gefitinib

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.

Group Type: EXPERIMENTAL

Gefitinib

Intervention Type: DRUG

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.

Interventions

Gefitinib

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.

Intervention Type: DRUG

Other Intervention Names

IRESSA®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ezra EW Cohen, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Northwestern University

Chicago, Illinois, United States

Countries

United States

References

Perez CA, Song H, Raez LE, Agulnik M, Grushko TA, Dekker A, Stenson K, Blair EA, Olopade OI, Seiwert TY, Vokes EE, Cohen EE. Phase II study of gefitinib adaptive dose escalation to skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck. Oral Oncol. 2012 Sep;48(9):887-92. doi: 10.1016/j.oraloncology.2012.03.020. Epub 2012 Apr 17.

Reference Type: RESULT

PMID: 22513208 (View on PubMed)

Other Identifiers

13503A

Identifier Type: -

Identifier Source: org_study_id