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

June 2, 2016 updated by: University of Chicago

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Drug: 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.
Other Names:
  • IRESSA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response (CR or PR), Stable Disease (SD), and Progressive Disease (PD) Rates
Time Frame: 8 weeks

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
Time Frame: 9 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Chicago

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Ezra EW Cohen, MD, University of Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (ACTUAL)

May 1, 2008

Study Completion (ACTUAL)

May 1, 2013

Study Registration Dates

First Submitted

August 17, 2007

First Submitted That Met QC Criteria

August 17, 2007

First Posted (ESTIMATE)

August 21, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

July 1, 2016

Last Update Submitted That Met QC Criteria

June 2, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13503A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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