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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00118248
First received: July 8, 2005
Last updated: April 4, 2014
Last verified: March 2014
  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:
  • Proportion of Patients Who Have Remained on Treatment and Progression-free at Least One Year After Start of 17-AAG (Tanespimycin) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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:
  • Overall Response [ Time Frame: Baseline, every 3 courses, and at the end of treatment study ] [ Designated as safety issue: No ]

    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 [ 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 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.

  • Overall Survival [ Time Frame: Every 3 months until progression, and then every 6 months up to 3 years ] [ 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 Kaplan-Meier method.

  • Toxicity [ Time Frame: Every 3 courses during treatment (median cycle number was 5 with a maximum of 38 cycles) ] [ Designated as safety issue: No ]
    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.


Enrollment: 41
Study Start Date: December 2004
Study Completion Date: April 2012
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy)
Patients receive 220 mg/m^2 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 at 220 mg/m^2 over 2 hours
Other Names:
  • 17-AAG
  • 17-Allylaminogeldanamycin

Detailed Description:

Analyses are performed separately for the cohort of patients with Medullary Thyroid Cancer and the cohort of patients with Differentiated Thyroid Cancer.

PRIMARY OBJECTIVES:

I. For each patient group, to estimate the proportion of patients who have not progressed or discontinue treatment within one year of starting tanespimycin (17AAG).

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: 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 discontinuation of study treatment,

  • patients who have not progressed on treatment are followed every 3 months until disease progression and then every 6 months for up to 3 years from study entry.
  • patients who have progressed on treatment are followed 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 central nervous system (CNS) metastases
  • Performance status - Eastern Cooperative Oncology Group (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)
  • Aspartate aminotransferase (AST) ≤ 1.5 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Corrected QT interval (QTc) < 450 msec for male patients (470 msec for female patients)
  • Left ventricular ejection fraction (LVEF) > 40% by multiple gated acquisition scan (MUGA)
  • diffusion capacity of lung for carbon monoxide (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 cytochrome P450 3A4 (CYP3A4) inhibitors allowed
  • No concurrent medications that prolong or may prolong QTc interval
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118248

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey Moley Washington University Early Recognition Center
  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
Results First Received: September 20, 2013
Last Updated: April 4, 2014
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 July 20, 2014