Tanespimycin in Treating Patients With Inoperable Locoregionally Advanced or Metastatic Thyroid Cancer

Phase 2

Completed

Conditions: Recurrent Thyroid Cancer
Stage IV Follicular Thyroid Cancer
Stage IV Papillary Thyroid Cancer
Thyroid Gland Medullary Carcinoma

Interventions: Drug: tanespimycin

Registration Number: NCT00118248

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is studying how well tanespimycin works in treating patients with inoperable locoregionally advanced or metastatic thyroid cancer. Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed Description: PRIMARY OBJECTIVES:

I. 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) (tanespimycin).

SECONDARY OBJECTIVES:

I. Determine the toxicity of this drug in these patients. Determine the 1-year progression-free rate in patients treated with this drug.

II. Determine the response rate and duration of response in patients treated with this drug.

III. Determine the time to treatment failure and time to subsequent therapy in patients treated with this drug.

IV. Determine the time to disease progression and overall survival of patients treated with this drug.

V. Correlate the incidence rate of RAS, RAF, and RET mutations with clinical outcome in patients treated with this drug.

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

Patients receive tanespimycin intravenously (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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

Inclusion Criteria

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
Performance status - ECOG 0-2
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9.0 g/dL
Bilirubin ≤ normal
Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
AST ≤ 1.5 times ULN
Creatinine ≤ 1.5 times ULN
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
No uncontrolled infection
No history of serious allergic reaction to eggs
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)
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
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])
More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
No other concurrent chemotherapy
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
More than 4 weeks since prior therapeutic surgery for the tumor
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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy)	tanespimycin	Patients receive tanespimycin 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.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients Who Have Remained on Treatment and Progression-free at Least One Year After Start of 17-AAG (Tanespimycin)	1 year	The one-year treatment failure free rate is 100% times the proportion of eligible patients who remain on treatment and are progression-free at least one year after treatment start. A 90% confidence interval for the one year treatment failure free rate was constructed using the properties of the binomial confidence interval. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients that are not classified as having a progression are termed progression-free.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Every 3 months until progression, and then every 6 months up to 3 years	Defined as the time from registration to date of last follow-up or death due to any cause. Estimated using the Kaplan-Meier method.
Toxicity	Every 3 courses during treatment (median cycle number was 5 with a maximum of 38 cycles)	Defined as the number of participants reporting grade 3 or higher adverse events that are classified as either possibly, probably, or definitely related to study treatment. Determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Overall Response	Baseline, every 3 courses, and at the end of treatment study	The number of responses were categorized and summarized independently within each of the patient groups. Participants were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.0. Complete Response (CR): Disappearance of all lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest dimension (LD) of target lesions taking as reference the baseline sum LD.
Progression-Free Survival	Every 3 months for up to 3 years	Defined as the time from registration to the date of progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients that are not classified as having a progression are termed progression-free. Estimated using the Kaplan-Meier method.