Tanespimycin in Treating Patients With Inoperable Locoregionally Advanced or Metastatic Thyroid Cancer
This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00118248
First received: July 8, 2005
Last updated: January 30, 2013
Last verified: August 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Recurrent Thyroid Cancer Stage IV Follicular Thyroid Cancer Stage IV Papillary Thyroid Cancer Thyroid Gland Medullary Carcinoma |
Drug: tanespimycin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Trial of 17-Allylaminogeldanamycin (17AAG) in Advanced Medullary and Differentiated Thyroid Carcinoma |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Treatment failure status [ Time Frame: 1 year ] [ Designated as safety issue: No ]Measured using Response Evaluation Criteria in Solid Tumors (RESIST) criteria. All patients meeting the eligibility criteria who have signed a consent form and begun treatment will be considered evaluable. Those who die will be considered to have failed treatment unless documented evidence clearly indicates no progression has occurred or that the death was in no way related to treatment.
- Success probability [ Time Frame: 1 year ] [ Designated as safety issue: No ]Estimated by the standard binomial estimator, i.e., the number of successes divided by the total number of evaluable patients, and 90% binomial confidence intervals.
Secondary Outcome Measures:
- Overall response [ Time Frame: Baseline, every 3 courses, and at the end of treatment study ] [ Designated as safety issue: No ]Calculated and summarized independently within each of the patient groups. 90% binomial confidence intervals will also be calculated.
- Time to disease progression [ Time Frame: Every 3 months for up to 3 years ] [ Designated as safety issue: No ]Defined as the time from registration to the date of progression or last follow-up, whichever comes first. Estimated using the method of Kaplan-Meier.
- Overall survival [ Time Frame: Every 3 months until progression, and then every 6 months ] [ Designated as safety issue: No ]Defined as the time from registration to date of last follow-up or death due to any cause. Estimated using the method of Kaplan-Meier.
- Time to treatment failure [ Time Frame: Every 3 months for up to 3 years ] [ Designated as safety issue: No ]Defined as the time from registration to the date the patient discontinues treatment, and its distribution will be estimated using the method of Kaplan-Meier.
- Time to subsequent therapy [ Time Frame: Every 3 months for up to 3 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan-Meier
- Duration of response [ Time Frame: Every 3 months for up to 3 years ] [ Designated as safety issue: No ]Calculated from the date of documentation of response (PR or CR) until the date of progression or last followup (whichever comes first) in the subset of patients with confirmed response.
- Incidence rate of the mutations evaluated from the tumor specimens (i.e. RAS, RAF, and RET) [ Time Frame: Baseline ] [ Designated as safety issue: No ]Performed after deoxyribonucleic acid (DNA) extraction from pre-treatment tissues and correlated with time to disease progression. Collected using two needle core biopsies. 95% binomial confidence intervals will be calculated.
- Toxicity [ Time Frame: Every 3 courses ] [ Designated as safety issue: No ]Defined as 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.
| Estimated Enrollment: | 72 |
| Study Start Date: | December 2004 |
| Primary Completion Date: | August 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (chemotherapy)
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.
|
Drug: tanespimycin
Given IV
Other Name: 17-AAG
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00118248 History of Changes |
| Obsolete Identifiers: | NCT01646944, NCT01664351 |
| Other Study ID Numbers: | NCI-2009-00063, MC0476, CDR0000433150 |
| Study First Received: | July 8, 2005 |
| Last Updated: | January 30, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Carcinoma Thyroid Neoplasms Thyroid Diseases Adenocarcinoma, Follicular Carcinoma, Medullary Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Endocrine Gland Neoplasms Neoplasms by Site |
Head and Neck Neoplasms Endocrine System Diseases Adenocarcinoma Carcinoma, Neuroendocrine Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Ductal, Lobular, and Medullary Neoplasms, Nerve Tissue |
ClinicalTrials.gov processed this record on May 19, 2013