Stage III Squamous Cell Carcinoma of the HypopharynxPhase 1NCT00033449
Gefitinib and Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III or Stage IV Head and Neck Cancer
A Phase 1 study testing gefitinib, radiation therapy and cisplatin in people with Stage III Squamous Cell Carcinoma of the Hypopharynx and Stage III Squamous Cell Carcinoma of the Larynx, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
- What is being tested?
- gefitinib, radiation therapy and cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2002to Apr 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 36Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gefitinibDrug
Also called Iressa, ZD 1839
Given orally
radiation therapyRadiation
Also called irradiation, radiotherapy, therapy, radiation
Undergo radiation therapy
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (gefitinib, radiation therapy, cisplatin) | Experimental | See detailed description. Receives: Drug: gefitinib; Radiation: radiation therapy; Drug: cisplatin; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of grade 4 or greater mucositis as scored by the National Cancer Institute (NCI) Common Toxicity Criteria v2.0
Descriptive statistics (mean, median, range, standard deviation [s.d.], percentage, as appropriate) will be obtained.
Measured: Up to 2 years
Incidence of grade 4 or greater skin toxicity as scored by the NCI Common Toxicity Criteria v2.0
Descriptive statistics (mean, median, range, s.d., percentage, as appropriate) will be obtained.
Measured: Up to 2 years
Incidence of any other grade 4 or greater toxicity as scored by the NCI Common Toxicity Criteria v2.0
Descriptive statistics (mean, median, range, s.d., percentage, as appropriate) will be obtained.
Measured: Up to 2 years
Secondary outcomes (5)
Primary tumor response rate as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Estimated with its 95% confidence interval.
Measured: 8 weeks
Response rates as assessed by the RECIST
Estimated with its 95% confidence interval.
Measured: Up to 5 years
Relapse-free survival rates
Measured: Up to 5 years
Overall survival rates
Estimated using Kaplan-Meier curves.
Measured: Up to 5 years
Biological effects of gefitinib within the primary tumor and skin
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startFeb 2002
- Primary completionApr 2010
Why it stopped: Administratively complete.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage III Squamous Cell Carcinoma of the HypopharynxStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David Raben, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00033449
- Sponsor's protocol ID
- NCI-2012-02462
- Other IDs
- UCHSC-01460, CDR0000069284
- Status last verified
- Jan 2013
- First submitted
- 9 Apr 2002
- Last updated
- 25 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Of ZD 1839 In Combination With Radiation And Chemotherapy In Locally Advanced Squamous Cell Carcinoma Of The Head And Neck
- ClinicalTrials.gov ID
- NCT00033449
- Acronym / sponsor ID
- NCI-2012-02462
- Conditions
- Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administratively complete.
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2002
- Primary completion
- Apr 2010 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (gefitinib, radiation therapy, cisplatin) | Experimental | Drug: gefitinib, Radiation: radiation therapy, Drug: cisplatin, Other: laboratory biomarker analysisSee detailed description. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Histologically confirmed locally advanced squamous cell carcinoma of the head and neck involving the oral cavity, oropharynx, hypopharynx, or supraglotticor glottic larynx
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gefitinibAlso: Iressa, ZD 1839Given orally | Drug | Treatment (gefitinib, radiation therapy, cisplatin) |
| radiation therapyAlso: irradiation, radiotherapy, therapy, radiationUndergo radiation therapy | Radiation | Treatment (gefitinib, radiation therapy, cisplatin) |
| cisplatinAlso: CACP, CDDP, CPDD, DDPGiven IV | Drug | Treatment (gefitinib, radiation therapy, cisplatin) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (gefitinib, radiation therapy, cisplatin) |
Primary outcome
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.
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.
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.
5 secondary outcomes
Primary tumor response rate as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: 8 weeks
Response rates as assessed by the RECIST
Time frame: Up to 5 years
Relapse-free survival rates
Time frame: Up to 5 years
Overall survival rates
Time frame: Up to 5 years
Biological effects of gefitinib within the primary tumor and skin
Time frame: Baseline
Results and safety
The study was stopped early (reason given: Administratively complete.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Raben principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing gefitinib, radiation therapy and cisplatin in people with Stage III Squamous Cell Carcinoma of the Hypopharynx and Stage III Squamous Cell Carcinoma of the Larynx, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Administratively complete.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2013.