Head and Neck Cancer
Conditions
Keywords
recurrent thyroid cancer, stage III follicular thyroid cancer, stage III papillary thyroid cancer, stage IV follicular thyroid cancer, stage IV papillary thyroid cancer, anaplastic thyroid cancer, thyroid gland medullary carcinoma
Brief summary
RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have locally advanced or metastatic thyroid cancer that did not respond to iodine therapy.
Detailed description
OBJECTIVES: Primary * Determine the all-measurable-disease response rate in patients with iodine-refractory locally advanced or metastatic thyroid cancer treated with gefitinib. Secondary * Determine the toxicity of this drug in these patients. * Determine progression-free and overall survival of patients treated with this drug. OUTLINE: This is an open-label study. Patients receive oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study.
Interventions
DRUGGefitinib
Taken orally once a day for duration of benefit. Treatment is continuous until there is evidence of disease progression or unacceptable toxicity.
Sponsors
National Cancer Institute (NCI)
Dana-Farber Cancer Institute
Brigham and Women's Hospital
AstraZeneca
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed thyroid cancer, metastatic or locally advanced, not amenable or refractory to local therapy and/or radioactive iodine, depending on the cell type. 2. Thyroid cancer that is unresponsive or refractory to radioactive iodine. All medullary and anaplastic thyroid carcinomas will be considered unresponsive on the basis of histopathologic diagnosis alone. Well-differentiated thyroid cancers (papillary and follicular) will be considered refractory if either there is no evidence of uptake on radioactive iodine scanning or tumor growth persists in spite of treatment with radioactive iodine. 3. Measurable disease. 4. Patient is at least 18 years of age. 5. Eastern Cooperative Oncology Group performance status of 0-2. 6. If female and of reproductive potential, a negative β-HCG (human chorionic gonadotropin) and use of effective birth control for the course of the study. 7. Patient is capable of providing signed, informed consent.
Exclusion criteria
1. Concurrent chemotherapy, concurrent systemic anticancer treatment, or concurrent radiation therapy. Patients will not be excluded from the study on the basis of prior radiation therapy. 2. Treatment with a non-approved or investigational drug within 30 days before Day 1 of trial treatment. 3. Currently pregnant or nursing. 4. Absolute neutrophil count \<1.5 × 109/L, platelet count \< 75 × 109/L, bilirubin \> 1.5 × normal, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × normal. 5. Serum creatinine greater than Common Toxicity Criteria (CTC) grade 2. 6. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampin, St John's Wort. 7. Concomitant use of systemic retinoids, cyclosporine, verapamil, diltiazem, nicardipine, nifedipine, nitrendipine, erythromycin, theophylline, ketoconazole, itraconazole, and antihistamines such as terfenadine and astemizole. 8. Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy. 9. Incomplete healing from previous oncologic or other major surgery. 10. Known severe hypersensitivity to ZD1839 or any of the excipients of this product. 11. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease). 12. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial. 13. Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Rate at 3, 6, and 12 Months | 3 Months, 6 Months, 1 Year | Response rate as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Tumor assessment is performed within 4 weeks of initiation of treatment and then every 8 weeks. If a patient has stable disease for four tumor assessments (6 months), then tumor assessment may occur every 4 months. If the patient continues to experience stable disease after 2 years, tumor assessments may occur every 6 months. If the patient continues to experience stable disease after 5 years, tumor assessments may occur once a year. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | Through study completion, on average 12 months | Drug related toxicity as assessed by NCI CTCAE that occurred in more than 10% of patients |
| Median Progression-free Survival | From the time of enrollment until disease progression or death, whichever came first | The median progression-free survival as assessed by RECIST criteria (Response Evaluation Criteria In Solid Tumors) measured from the time of enrollment until disease progression or death. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of new lesions. |
| Overall Survival | 5 years | The median overall survival time, measured from the time of enrollment until death. |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled from Massachusetts General Hospital and the Dana-Farber Cancer Institute
Participants by arm
| Arm | Count |
|---|---|
| Gefitinib 250mg Gefitinib: Taken orally once a day for duration of benefit. Treatment is continuous until there is evidence of disease progression or unacceptable toxicity. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Gefitinib 250mg | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 13 Participants | — |
| Age, Categorical Between 18 and 65 years | 14 Participants | — |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 9.5 | — |
| ECOG Performance Status 0-1 | 25 Participants | — |
| ECOG Performance Status 2 | 2 Participants | — |
| Histology Anaplastic | 5 Participants | — |
| Histology Follicular | 6 Participants | — |
| Histology Hürthle cell | 1 Participants | — |
| Histology Medullary | 4 Participants | — |
| Histology Papillary | 11 Participants | — |
| Metastatic sites Lung + extra-pulmonary metastases | 15 Participants | — |
| Metastatic sites Lung-only | 10 Participants | — |
| Prior therapy Chemotherapy | 6 participants | — |
| Prior therapy External beam radiotherapy | 23 participants | — |
| Prior therapy Radioactive iodine | 17 participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 27 participants | — |
| Sex: Female, Male Female | 11 Participants | — |
| Sex: Female, Male Male | 16 Participants | — |
| Stage Locally Advanced | 2 Participants | — |
| Stage Metastatic | 25 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 27 |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 6 / 27 |
Outcome results
Primary
Objective Tumor Response Rate at 3, 6, and 12 Months
Response rate as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Tumor assessment is performed within 4 weeks of initiation of treatment and then every 8 weeks. If a patient has stable disease for four tumor assessments (6 months), then tumor assessment may occur every 4 months. If the patient continues to experience stable disease after 2 years, tumor assessments may occur every 6 months. If the patient continues to experience stable disease after 5 years, tumor assessments may occur once a year. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD
Time frame: 3 Months, 6 Months, 1 Year
Population: Two patients lost to follow-up prior to assessment of tumor response
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Complete Response : 3 Months | 0 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Partial Response : 3 Months | 0 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Stable Disease : 3 Months | 12 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Progressive Disease : 3 Months | 13 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Complete Response : 6 Months | 0 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Partial Response : 6 Months | 0 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Stable Disease : 6 Months | 6 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Progressive Disease : 6 Months | 19 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Complete Response : 12 Months | 0 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Partial Response : 12 Months | 0 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Stable Disease : 12 Months | 3 participants |
| Gefitinib 250mg | Objective Tumor Response Rate at 3, 6, and 12 Months | Progressive Disease : 12 Months | 22 participants |
Secondary
Median Progression-free Survival
The median progression-free survival as assessed by RECIST criteria (Response Evaluation Criteria In Solid Tumors) measured from the time of enrollment until disease progression or death. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of new lesions.
Time frame: From the time of enrollment until disease progression or death, whichever came first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gefitinib 250mg | Median Progression-free Survival | 3.7 Months |
Secondary
Overall Survival
The median overall survival time, measured from the time of enrollment until death.
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gefitinib 250mg | Overall Survival | 17.5 Months |
Secondary
Toxicity
Drug related toxicity as assessed by NCI CTCAE that occurred in more than 10% of patients
Time frame: Through study completion, on average 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefitinib 250mg | Toxicity | Rash: Grade 0 | 13 participants |
| Gefitinib 250mg | Toxicity | Rash: Grade 1 | 9 participants |
| Gefitinib 250mg | Toxicity | Rash: Grade 2 | 3 participants |
| Gefitinib 250mg | Toxicity | Rash: Grade 3 | 2 participants |
| Gefitinib 250mg | Toxicity | Diarrhea: Grade 0 | 16 participants |
| Gefitinib 250mg | Toxicity | Diarrhea: Grade 1 | 8 participants |
| Gefitinib 250mg | Toxicity | Diarrhea: Grade 2 | 2 participants |
| Gefitinib 250mg | Toxicity | Diarrhea: Grade 3 | 1 participants |
| Gefitinib 250mg | Toxicity | Nausea: Grade 0 | 22 participants |
| Gefitinib 250mg | Toxicity | Nausea: Grade 1 | 5 participants |
| Gefitinib 250mg | Toxicity | Anorexia: Grade 0 | 24 participants |
| Gefitinib 250mg | Toxicity | Anorexia: Grade 1 | 3 participants |