Gefitinib in Treating Patients With Locally Advanced or Metastatic Thyroid Cancer That Did Not Respond to Iodine Therapy

A Phase II Study of ZD 1839 (IRESSA®) in Patients With Advanced Thyroid Cancer

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Gefitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gefitinib 250mg	Drug: Gefitinib; Taken orally once a day for duration of benefit. Treatment is continuous until there is evidence of disease progression or unacceptable toxicity.; Other Names: ZD1839; IRESSA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	3 Months, 6 Months, 1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Drug related toxicity as assessed by NCI CTCAE that occurred in more than 10% of patients	Through study completion, on average 12 months
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.	From the time of enrollment until disease progression or death, whichever came first
Overall Survival	The median overall survival time, measured from the time of enrollment until death.	5 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Cancer Institute (NCI); Dana-Farber Cancer Institute; AstraZeneca; Brigham and Women's Hospital
• Investigators: Principal Investigator: John R Clark, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Pennell NA, Daniels GH, Haddad RI, Ross DS, Evans T, Wirth LJ, Fidias PH, Temel JS, Gurubhagavatula S, Heist RS, Clark JR, Lynch TJ. A phase II study of gefitinib in patients with advanced thyroid cancer. Thyroid. 2008 Mar;18(3):317-23. doi: 10.1089/thy.2007.0120.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2003
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 8, 2004
• First Posted (Estimate): November 9, 2004

Study Record Updates

• Last Update Posted (Actual): May 31, 2017
• Last Update Submitted That Met QC Criteria: May 2, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: anaplastic thyroid cancer; stage IV papillary thyroid cancer; stage IV follicular thyroid cancer; thyroid gland medullary carcinoma; recurrent thyroid cancer; stage III follicular thyroid cancer; stage III papillary thyroid cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Thyroid Diseases; Head and Neck Neoplasms; Thyroid Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: 02-220; P30CA006516 (U.S. NIH Grant/Contract); ZENECA-IRUSIRES0165 (Other Identifier: AstraZeneca); CDR0000393510 (Registry Identifier: NCI PDQ)