FindTrial
Sign In

IRESSA™ (Gefitinib) With Cisplatin Plus Radiotherapy for the Treatment of Previously Untreated Unresected Late Stage III/IV Non-Metastatic Head and Neck Squamous Cell Carcinoma

A Phase 2 Randomised, Double-Blind, Placebo-Controlled, Multicentre Comparative Study of Gefitinib 250 mg or 500 mg (IRESSA™) Given Either Continuously or Concomitantly With Cisplatin Plus Radiotherapy for the Treatment of Patients With Previously Untreated Unresected Late Stage III/IV Non-Metastatic Head and Neck Squamous Cell Carcinoma

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00229723
Enrollment
224
Registered
2005-09-30
Start date
2004-11-30
Completion date
2008-06-30
Last updated
2009-08-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neoplasms, Squamous Cell

Keywords

Head and Neck Squamous Cell Carcinoma, Head and Neck Squamous Cell Cancer, Squamous Cell Carcinoma, Squamous Cell Cancer

Brief summary

The primary purpose of this study is to assess the effectiveness of ZD1839 250 mg and 500 mg when given either concomitantly or as maintenance to a standard therapy of radiotherapy (X-rays) plus chemotherapy (cisplatin) in terms of local disease control (progression-free) rate at 2 years.

Interventions

DRUGgefitinib (Iressa)

250 mg oral tablet

DRUGcisplatin

intravenous infusion

RADIATIONradiotherapy

radiation therapy

DRUGGefitinib (Iressa)

500 mg oral tablet

Sponsors

AstraZeneca
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Histologically or cytologically confirmed stage III or IVA squamous cell carcinoma of the head and neck * No prior surgery or chemotherapy/biological therapy/radiation therapy * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) * Life expectancy of more than 12 weeks

Exclusion criteria

* Cancers of the nasal space, oral cavity and larynx; or certain lung diseases. * Abnormal blood chemistry; uncontrolled respiratory, cardiac, hepatic, or renal disease; or coexisting malignancies.

Design outcomes

Primary

MeasureTime frameDescription
Local Disease Control Rate at 2 YearsAssessed at 2 yrs. Tumour assessments (clinical & by CT/MRI) were carried out during screening & regularly throughout the study until disease progression (as defined by Response evaluation criteria in solid tumours (RECIST)).A patient demonstrated local disease control at 2 years if there was no evidence of failure of treatment. Failure was defined as the patient having objective disease progression (as per RECIST) inside the original irradiated area, at an isodose level (between 20% and 95%), or death.

Secondary

MeasureTime frameDescription
Complete ResponseAssessed at 2 years. Clinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progression.A patient was deemed to be a complete responder if the RECIST criteria for complete response were satisfied at any time during the study.
Tumour Response (Complete Response + Partial Response)Assessed at 2 years. Clinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progressionA patient was deemed to be have a tumour response if the RECIST criteria for complete response or partial response were satisfied at any time during the study.
Local Disease Control Rate at 1 YearAssessed after 1 year. Tumour assessments (clinical and by CT/MRI) were carried out during screening & regularly throughout the study until disease progression (as defined by RECIST).A patient demonstrated local disease control at 1 year if there was no evidence of failure of treatment. Failure was defined as the patient having objective disease progression (as per RECIST) inside the original irradiated area, at an isodose level (between 20% and 95%), or death.
Overall SurvivalOverall survival assessed at 2 yearsPercentage of participants who are alive at 2 years (calculated using the Kaplan-Meier method, which allows for patients who do not have complete follow-up (censored observations)).
Safety and TolerabilityAssessed over two years—
Progression Free SurvivalClinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progression (as defined by RECIST)Percentage of participants who are progression free at 2 years (calculated using the Kaplan-Meier method, which allows for censored observations for example those lost to follow-up). A patient is said to have progressed if they have progression of target or non-target lesions or evidence of any new lesions (as defined by RECIST).

Countries

Belgium, Czechia, Germany, India, Poland, Serbia, Taiwan, United States

Participant flow

Recruitment details

In total, 226 patients from 26 centres in 8 countries were randomized to receive study medication, the first patient was enrolled into the study on 13 November 2004 and the last patient completed the study on 27 June 2008. Patients were to be followed up for a maximum of two years (± 12 weeks) after randomization.

Participants by arm

ArmCount
Placebo/Placebo
Concomitant placebo (plus cisplatin and radiotherapy) followed by placebo as maintenance therapy
60
250mg/Placebo
Concomitant gefitinib 250 mg (plus cisplatin and radiotherapy) followed by placebo as maintenance therapy
24
500mg/Placebo
Concomitant gefitinib 500 mg (plus cisplatin and radiotherapy) followed by placebo as maintenance therapy
31
250mg/250mg
Concomitant gefitinib 250 mg (plus cisplatin and radiotherapy) followed by gefitinib 250 mg as maintenance therapy
31
500mg/500mg
Concomitant gefitinib 500 mg (plus cisplatin and radiotherapy) followed by gefitinib 500 mg as maintenance therapy
24
Placebo/250mg
Concomitant placebo (plus cisplatin and radiotherapy) followed by gefitinib 250 mg as maintenance therapy
34
Placebo/500mg
Concomitant placebo (plus cisplatin and radiotherapy) followed by gefitinib 500 mg as maintenance therapy
22
Total226

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006
Concomitant PhaseAdverse Event4252012
Concomitant PhaseClinical progression0000001
Concomitant PhaseInformed consent withdrawn3202000
Concomitant PhaseLost to Follow-up0000100
Concomitant PhaseObjective disease progression0000000
Concomitant PhaseOther3011020
Concomitant PhaseSevere non-compliance0100100
Maintenance PhaseAdverse Event7214752
Maintenance PhaseClinical progression4122111
Maintenance PhaseInformed consent withdrawn1001110
Maintenance PhaseLost to Follow-up0122001
Maintenance PhaseObjective disease progression5536295
Maintenance PhaseOther5412331
Maintenance PhaseSevere non-compliance3100100

Baseline characteristics

Characteristic250mg/PlaceboTotalPlacebo/PlaceboPlacebo/500mgPlacebo/250mg500mg/500mg250mg/250mg500mg/Placebo
Age Continuous52.5 Years53.2 Years53.1 Years54.9 Years53.4 Years50.8 Years54.3 Years53.4 Years
Original site of primary cancer
Hypopharynx
9 Participants67 Participants19 Participants4 Participants12 Participants4 Participants10 Participants9 Participants
Original site of primary cancer
Larynx
2 Participants27 Participants10 Participants3 Participants4 Participants3 Participants1 Participants4 Participants
Original site of primary cancer
Oral cavity
0 Participants15 Participants4 Participants3 Participants2 Participants3 Participants1 Participants2 Participants
Original site of primary cancer
Oropharynx
12 Participants109 Participants26 Participants10 Participants15 Participants13 Participants18 Participants15 Participants
Original site of primary cancer
Oropharynx / Hypopharynx
0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants
Original site of primary cancer
Other
1 Participants7 Participants1 Participants2 Participants1 Participants1 Participants0 Participants1 Participants
Race/Ethnicity, Customized
Caucasian (includes Indian)
22 Participants210 Participants56 Participants20 Participants32 Participants22 Participants29 Participants29 Participants
Race/Ethnicity, Customized
Oriental
2 Participants16 Participants4 Participants2 Participants2 Participants2 Participants2 Participants2 Participants
Sex: Female, Male
Female
3 Participants28 Participants8 Participants4 Participants1 Participants5 Participants4 Participants3 Participants
Sex: Female, Male
Male
21 Participants198 Participants52 Participants18 Participants33 Participants19 Participants27 Participants28 Participants
Stage of disease at entry to study
Stage III
7 Participants49 Participants10 Participants8 Participants6 Participants4 Participants7 Participants7 Participants
Stage of disease at entry to study
Stage IV (All these patients had Stage IVa cancer)
17 Participants177 Participants50 Participants14 Participants28 Participants20 Participants24 Participants24 Participants
WHO Performance Status
0 (Normal activity)
14 Participants160 Participants41 Participants16 Participants24 Participants17 Participants24 Participants24 Participants
WHO Performance Status
1 (Restricted activity)
8 Participants48 Participants13 Participants5 Participants6 Participants6 Participants4 Participants6 Participants
WHO Performance Status
2 (in bed ≤ 50% of the time)
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
WHO Performance Status
3 (in bed > 50% of the time)
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
WHO Performance Status
4 (100% Bed ridden)
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
WHO Performance Status
Not recorded
2 Participants18 Participants6 Participants1 Participants4 Participants1 Participants3 Participants1 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —— / —— / —
other
Total, other adverse events
58 / —23 / —30 / —30 / —23 / —32 / —21 / —
serious
Total, serious adverse events
23 / —9 / —21 / —15 / —14 / —16 / —11 / —

Outcome results

Primary

Local Disease Control Rate at 2 Years

A patient demonstrated local disease control at 2 years if there was no evidence of failure of treatment. Failure was defined as the patient having objective disease progression (as per RECIST) inside the original irradiated area, at an isodose level (between 20% and 95%), or death.

Time frame: Assessed at 2 yrs. Tumour assessments (clinical & by CT/MRI) were carried out during screening & regularly throughout the study until disease progression (as defined by Response evaluation criteria in solid tumours (RECIST)).

ArmMeasureValue (NUMBER)
Placebo/PlaceboLocal Disease Control Rate at 2 Years21 Participants
250mg/PlaceboLocal Disease Control Rate at 2 Years7 Participants
500mg/PlaceboLocal Disease Control Rate at 2 Years15 Participants
250mg/250mgLocal Disease Control Rate at 2 Years7 Participants
500mg/500mgLocal Disease Control Rate at 2 Years7 Participants
Placebo/250mgLocal Disease Control Rate at 2 Years9 Participants
Placebo/500mgLocal Disease Control Rate at 2 Years9 Participants
Secondary

Complete Response

A patient was deemed to be a complete responder if the RECIST criteria for complete response were satisfied at any time during the study.

Time frame: Assessed at 2 years. Clinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progression.

ArmMeasureValue (NUMBER)
Placebo/PlaceboComplete Response28 Participants
250mg/PlaceboComplete Response7 Participants
500mg/PlaceboComplete Response11 Participants
250mg/250mgComplete Response13 Participants
500mg/500mgComplete Response6 Participants
Placebo/250mgComplete Response14 Participants
Placebo/500mgComplete Response11 Participants
Secondary

Local Disease Control Rate at 1 Year

A patient demonstrated local disease control at 1 year if there was no evidence of failure of treatment. Failure was defined as the patient having objective disease progression (as per RECIST) inside the original irradiated area, at an isodose level (between 20% and 95%), or death.

Time frame: Assessed after 1 year. Tumour assessments (clinical and by CT/MRI) were carried out during screening & regularly throughout the study until disease progression (as defined by RECIST).

ArmMeasureValue (NUMBER)
Placebo/PlaceboLocal Disease Control Rate at 1 Year27 Participants
250mg/PlaceboLocal Disease Control Rate at 1 Year8 Participants
500mg/PlaceboLocal Disease Control Rate at 1 Year16 Participants
250mg/250mgLocal Disease Control Rate at 1 Year13 Participants
500mg/500mgLocal Disease Control Rate at 1 Year10 Participants
Placebo/250mgLocal Disease Control Rate at 1 Year14 Participants
Placebo/500mgLocal Disease Control Rate at 1 Year10 Participants
Secondary

Overall Survival

Percentage of participants who are alive at 2 years (calculated using the Kaplan-Meier method, which allows for patients who do not have complete follow-up (censored observations)).

Time frame: Overall survival assessed at 2 years

ArmMeasureValue (NUMBER)
Placebo/PlaceboOverall Survival64.6 Percentage of participants
250mg/PlaceboOverall Survival60.0 Percentage of participants
500mg/PlaceboOverall Survival74.8 Percentage of participants
250mg/250mgOverall Survival43.2 Percentage of participants
500mg/500mgOverall Survival49.4 Percentage of participants
Placebo/250mgOverall Survival48.2 Percentage of participants
Placebo/500mgOverall Survival61.1 Percentage of participants
Secondary

Progression Free Survival

Percentage of participants who are progression free at 2 years (calculated using the Kaplan-Meier method, which allows for censored observations for example those lost to follow-up). A patient is said to have progressed if they have progression of target or non-target lesions or evidence of any new lesions (as defined by RECIST).

Time frame: Clinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progression (as defined by RECIST)

ArmMeasureValue (NUMBER)
Placebo/PlaceboProgression Free Survival41.9 Percentage of participants
250mg/PlaceboProgression Free Survival43.1 Percentage of participants
500mg/PlaceboProgression Free Survival58.1 Percentage of participants
250mg/250mgProgression Free Survival31.2 Percentage of participants
500mg/500mgProgression Free Survival43.1 Percentage of participants
Placebo/250mgProgression Free Survival30.0 Percentage of participants
Placebo/500mgProgression Free Survival42.9 Percentage of participants
Secondary

Safety and Tolerability

Time frame: Assessed over two years

Secondary

Tumour Response (Complete Response + Partial Response)

A patient was deemed to be have a tumour response if the RECIST criteria for complete response or partial response were satisfied at any time during the study.

Time frame: Assessed at 2 years. Clinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progression

ArmMeasureValue (NUMBER)
Placebo/PlaceboTumour Response (Complete Response + Partial Response)34 Participants
250mg/PlaceboTumour Response (Complete Response + Partial Response)11 Participants
500mg/PlaceboTumour Response (Complete Response + Partial Response)17 Participants
250mg/250mgTumour Response (Complete Response + Partial Response)18 Participants
500mg/500mgTumour Response (Complete Response + Partial Response)11 Participants
Placebo/250mgTumour Response (Complete Response + Partial Response)22 Participants
Placebo/500mgTumour Response (Complete Response + Partial Response)14 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026