Gefitinib and Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III or Stage IV Head and Neck Cancer

January 24, 2013 updated by: National Cancer Institute (NCI)

A Phase I Study Of ZD 1839 In Combination With Radiation And Chemotherapy In Locally Advanced Squamous Cell Carcinoma Of The Head And Neck

This phase I trial is studying the side effects and best dose of gefitinib when given together with radiation therapy with or without cisplatin in treating patients with stage III or stage IV head and neck cancer. Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of cancer. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and radiation therapy with cisplatin may kill more tumor cells

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To establish the safety profile of daily oral administration of ZD1839 ("Iressa", AstraZeneca, Inc.) that can be given with concurrent irradiation alone or combined concurrently with weekly cisplatin in previously untreated patients with locally advanced HNSCC, AJCC clinical stage III-IVB, deemed not suitable for surgery. Hence, the maximum-tolerated dose of ZD1839 will be determined.

II. To delineate and quantitate any dose-dependent local and or systemic toxicities of ZD1839 given concurrently with irradiation or combined concurrently with weekly cisplatin to patients with locally advanced, HNSCC, AJCC stage III-IVB, deemed not suitable for surgery.

III. To determine the feasibility and toxicity profile of protracted continuous daily dosing of ZD1839 beginning 8 weeks after the completion of the head and neck radiation therapy for a period not to exceed 2 years.

SECONDARY OBJECTIVES:

I. Secondary endpoints will include determination of the response rates, relapse-free survival rates and overall survival rates for this group of patients.

II. To perform correlative studies assessing the biological effects of ZD1839 within the primary tumor.

OUTLINE: This is a multicenter, dose-escalation study of gefitinib.

All patients receive oral gefitinib once daily beginning at least 7 days before and continuing throughout radiotherapy or chemoradiotherapy in the absence of disease progression or unacceptable toxicity. Patients are entered into 1 of 5 levels.

Level I: Patients undergo concurrent boost radiotherapy 5 days per week comprising once daily radiotherapy for 3.5 weeks followed by twice daily radiotherapy for 2.5 weeks.

Level II: Patients receive escalated dose of gefitinib and undergo radiotherapy as in level I.

Level III: Patients receive original dose of gefitinib, undergo standard fractionation radiotherapy comprising once daily radiotherapy 5 days per week for 7 weeks, and receive cisplatin IV over 30-60 minutes at the beginning of each week of radiotherapy.

Level IV: Patients receive escalated dose of gefitinib as in level II and undergo radiotherapy and chemotherapy as in level III.

Level V: Patients receive the maximum tolerated dose (MTD) of gefitinib, radiotherapy 5 days a week for 6 weeks, and chemotherapy as in level III.

Patients with clinical or radiologic evidence of residual disease are required to undergo neck dissection approximately 8 weeks after completion of radiotherapy or chemoradiotherapy.

Patients resume oral gefitinib daily beginning 8 weeks after the completion of radiotherapy or chemoradiotherapy (12 weeks for patients who undergo neck dissection) and continuing for 2 years in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients are enrolled sequentially beginning at level I until the MTD of gefitinib is determined. The MTD is the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Twelve additional patients receive the MTD of gefitinib in combination with radiotherapy with or without cisplatin.

Patients are followed every 6 months for at least 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

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
    • Colorado
      • Denver, Colorado, United States, 80217-3364
        • University Of Colorado

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed locally advanced squamous cell carcinoma of the head and neck involving the oral cavity, oropharynx, hypopharynx, or supraglotticor glottic larynx

    • Unresectable disease

      • Medically inoperable resectable disease allowed

    • Stage III or IV

      • No distant metastases
  • Only patients with intermediate stage disease (T1-2, N1-N2a or T3, N0-1) are eligible for radiotherapy alone with gefitinib
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 6 months
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9 g/dL
  • Bilirubin normal
  • AST and ALT no greater than 2.5 times upper limit of normal
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Medically suitable to withstand a course of definitive radiotherapy
  • No ongoing or active infection
  • No other malignancy within the past 3 years except basal cell skin cancer or carcinoma in situ of the cervix
  • No prior allergic reactions to compounds of similar chemical or biological composition to gefitinib or other study agents
  • No uncontrolled concurrent medical or psychiatric illness or social situation that would preclude study participation
  • No prior monoclonal antibodies with potential epidermal growth factor receptor (EGFR) binding therapy
  • No prior chemotherapy
  • No prior radiotherapy
  • No prior surgery except biopsy
  • No prior anti-EGFR therapy including prior tyrosine kinase inhibitors
  • No concurrent combination anti-retroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent commercial or investigational agents or therapies intended to treat the malignancy

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment (gefitinib, radiation therapy, cisplatin)
See detailed description.
Other: laboratory biomarker analysis
Correlative studies
Drug: gefitinib
Given orally
Other Names:
  • Iressa
  • ZD 1839
Drug: cisplatin
Given IV
Other Names:
  • CDDP
  • DDP
  • CACP
  • CPDD
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of grade 4 or greater mucositis as scored by the National Cancer Institute (NCI) Common Toxicity Criteria v2.0
Time Frame: Up to 2 years
Descriptive statistics (mean, median, range, standard deviation [s.d.], percentage, as appropriate) will be obtained.
Up to 2 years
Incidence of grade 4 or greater skin toxicity as scored by the NCI Common Toxicity Criteria v2.0
Time Frame: Up to 2 years
Descriptive statistics (mean, median, range, s.d., percentage, as appropriate) will be obtained.
Up to 2 years
Incidence of any other grade 4 or greater toxicity as scored by the NCI Common Toxicity Criteria v2.0
Time Frame: Up to 2 years
Descriptive statistics (mean, median, range, s.d., percentage, as appropriate) will be obtained.
Up to 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Primary tumor response rate as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: 8 weeks
Estimated with its 95% confidence interval.
8 weeks
Response rates as assessed by the RECIST
Time Frame: Up to 5 years
Estimated with its 95% confidence interval.
Up to 5 years
Relapse-free survival rates
Time Frame: Up to 5 years
Up to 5 years
Overall survival rates
Time Frame: Up to 5 years
Estimated using Kaplan-Meier curves.
Up to 5 years
Biological effects of gefitinib within the primary tumor and skin
Time Frame: Baseline
Examined using linear or nonlinear mixed models. Reductions of labeling scores that are of prognostic importance will be determined by relating labeling scores to survival scores by statistical methods such as the Cox proportional hazards regression model.
Baseline

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David Raben, University of Colorado, Denver

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2002

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 9, 2002

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2003

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 25, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NCI-2012-02462
  • UCHSC-01460
  • CDR0000069284 (Registry Identifier: PDQ (Physician Data Query))

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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