Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

17-AAG in Treating Patients With Inoperable Locoregionally Advanced or Metastatic Thyroid Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	MAYO-MC0476 6482, NCI-6482, NCT00118248, JHOC-JS0652, JHOC-B/06/174

Special Category: NCI Web site featured trial

Objectives

Primary

1. Determine the 1-year treatment failure rate in patients with inoperable locoregionally advanced or metastatic medullary or differentiated thyroid carcinoma treated with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

Secondary

1. Determine the toxicity of this drug in these patients.
2. Determine the 1-year progression-free rate in patients treated with this drug.
3. Determine the response rate and duration of response in patients treated with this drug.
4. Determine the time to treatment failure and time to subsequent therapy in patients treated with this drug.
5. Determine the time to disease progression and overall survival of patients treated with this drug.
6. Correlate the incidence rate of RAS, RAF, and RET mutations with clinical outcome in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Diagnosis of thyroid carcinoma of 1 of the following types:
  • Medullary
  • Differentiated
    • Iodine I 131-resistant disease, defined as failure to incorporate and/or progression of measurable disease after treatment with iodine I 131



• Inoperable locoregionally advanced or metastatic disease



• Measurable disease, defined as ≥ 1 lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan



• No active CNS metastases

Prior/Concurrent Therapy:

Biologic therapy

• More than 4 weeks since prior and no concurrent immunotherapy
• More than 4 weeks since prior biologic therapy
• No concurrent routine or prophylactic colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior and no concurrent radiotherapy
• More than 4 weeks since prior radiopharmaceuticals
• No prior radiotherapy to > 25% of bone marrow
• No prior radiotherapy that potentially included the heart in the field (i.e., mantle) or chest

Surgery

• More than 4 weeks since prior therapeutic surgery for the tumor

Other

• More than 3 months since prior sublingual nitroglycerin
• No other concurrent investigational ancillary therapy
• Concurrent CYP3A4 inhibitors allowed
• No concurrent medications that prolong or may prolong QTc interval

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• Bilirubin ≤ normal
• Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
• AST ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• QTc < 450 msec for male patients (470 msec for female patients)
• LVEF > 40% by MUGA
• DLCO ≥ 80%
• No cardiac symptoms ≥ grade 2
• No active ischemic heart disease within the past year
• No congenital long QT syndrome
• No left bundle branch block
• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• No myocardial infarction within the past year
• No New York Heart Association class III or IV congestive heart failure
• No poorly controlled angina
• No history of angina (of any sort) within the past 6 months
• No history of uncontrolled dysrhythmias or requiring antiarrhythmic drugs
• No history of cardiac toxicity after treatment with anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)
• No other significant cardiac disease

Immunologic

• No uncontrolled infection
• No history of serious allergic reaction to eggs

Pulmonary

• No pulmonary symptoms ≥ grade 2
• No symptomatic pulmonary disease requiring medication including the following:
  • Dyspnea on or off exertion
  • Paroxysmal nocturnal dyspnea
  • Oxygen requirement
  • Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease)
• No home oxygen need meeting the Medicare criteria
• No history of pulmonary toxicity after treatment with anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinoma
• No active seizure disorder

Expected Enrollment

A total of 28-72 patients (14-36 per stratum) will be accrued for this study within 24 months.

Outcomes

Treatment failure at 1 year

Toxicity
Overall survival
Time to disease progression
Overall response rate (complete and partial)
Correlation of the incidence rate of RAS, RAF, and RET mutations with clinical response
Time to treatment failure

Outline

This is a multicenter study. Patients are stratified according to type of thyroid carcinoma (medullary vs differentiated).

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years from study entry.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Jeffrey Moley, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Robert Smallridge, MD, Protocol co-chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

Related Information

Featured trial article

Registry Information
Official Title		A Phase II Trial of 17-Allylaminogeldanamycin (17AAG) in Advanced Medullary and Differentiated Carcinoma of the Thyroid
Trial Start Date		2004-12-08
Trial Completion Date		2006-06-01 (estimated)
Registered in ClinicalTrials.gov		NCT00118248
Date Submitted to PDQ		2005-05-03
Information Last Verified		2009-01-13
NCI Grant/Contract Number		CA15083, CM17104

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