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

Primary Purpose

Head and Neck Neoplasms

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gefitinib
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Neoplasms focused on measuring cancer, squamous cell, carcinoma, head, neck

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Miami Sylvester Comprehensive Cancer Center
  • Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gefitinib

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

First Posted
August 17, 2007
Last Updated
June 2, 2016
Sponsor
University of Chicago
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00519077
Brief Title
Phase II Study of Skin Toxicity Dosing of IRESSA (Gefitinib) in Squamous Cell Carcinoma of the Head and Neck
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Neoplasms
Keywords
cancer, squamous cell, carcinoma, head, neck

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gefitinib
Arm Type
Experimental
Arm Description
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
Intervention Name(s)
Gefitinib
Other Intervention Name(s)
IRESSA®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Response (CR or PR), Stable Disease (SD), and Progressive Disease (PD) Rates
Description
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
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Median Progression-free Survival Time
Description
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.
Time Frame
9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ezra EW Cohen, MD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22513208
Citation
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.
Results Reference
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Phase II Study of Skin Toxicity Dosing of IRESSA (Gefitinib) in Squamous Cell Carcinoma of the Head and Neck

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