Bortezomib in Treating Patients With Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

A Phase II Study of Bortezomib in Metastatic Papillary Thyroid Carcinoma or Follicular Thyroid Carcinoma

This phase II trial is studying how well bortezomib works in treating patients with metastatic thyroid cancer that did not respond to radioactive iodine therapy. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Study Overview

• Status: Completed
• Conditions: Insular Thyroid Cancer; Recurrent Thyroid Cancer; Stage II Follicular Thyroid Cancer; Stage II Papillary Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer
• Intervention / Treatment: Drug: Bortezomib

Detailed Description

PRIMARY OBJECTIVE:

I. Determine the efficacy of bortezomib, in terms of tumor response rate, in patients with metastatic papillary or follicular thyroid cancer unresponsive to prior radioiodine therapy.

SECONDARY OBJECTIVE:

I. Determine the clinical activity of this drug, in terms of progression-free survival, in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study. Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado at Denver Health Sciences Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Lombardi Comprehensive Cancer Center at Georgetown University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Harvard Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson 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:

• The Eastern Cooperative Oncology Group (ECOG) 0-2 OR Karnofsky 60-100%
• Platelet count >= 100,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• White Blood Count (WBC) >= 3,000/mm^3
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) =< 2.5 times upper limit of normal
• Bilirubin normal
• No symptomatic congestive heart failure
• Creatinine normal OR creatinine clearance >= 60 mL/min
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• At least 4 weeks since prior chemotherapy
• No more than 2 prior chemotherapy regimens
• At least 6 months since prior external beam radiotherapy for locoregional disease in the thyroid bed or to the cervical or upper mediastinal lymph nodes (dose =< 6,000 cGy)
• At least 6 months since prior radioiodine therapy
• No prior external radiotherapy to the measured tumor
• Prior thyroidectomy allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• Unresponsive to prior radioiodine therapy
• Histologically confirmed differentiated thyroid cancer-papillary or follicular type, including, but not limited to, any of the following variants: hurthle cell (oxyphilic), insular, columnar cell, tall cell
• Metastatic disease
• At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
• No prior radiotherapy to the only measurable lesion
• No radioiodine uptake in the measured metastatic tumor by radioiodine scan (Note: Must have had >= 1 radioiodine scan since the last radioiodine treatment)
• No known brain metastases

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: Bortezomib; Bortezomib 1.3 mg/m^2 intravenous (IV) at over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses.	Drug: Bortezomib; Administered IV at the dose of 1.3 mg/m^2 on a twice-weekly schedule for 2 consecutive weeks on days 1, 4, 8, and 11, followed by a 10 day rest period on days 12-21 (one cycle). In the absence of clinical progression, treatment continued for a minimum of 4 treatment cycles (or 12 weeks).; Other Names: MLN341; LDP 341; VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response Rate Assessed by RECIST	Response Rate calculated as number of participants with Complete or Partial Response divided by total participants. Baseline scan and confirmatory scans obtained 6 weeks following initial documentation of objective response using Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in sum longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.	Baseline to 12 weeks
Participant Tumor Response Assessed by RECIST	Baseline scan and confirmatory scans obtained 6 weeks following initial documentation of objective response using Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in sum longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.	Baseline to 12 weeks (minimum of 4 treatment cycles (or 12 weeks))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Assessed by RECIST	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	At 6 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Steven Sherman, The University Of Texas MD Anderson Cancer Center

Publications and helpful links

Helpful Links

• The University of Texas MD Anderson Cancer Center Official Website

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: March 3, 2005
• First Submitted That Met QC Criteria: March 3, 2005
• First Posted (Estimate): March 4, 2005

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: National Thyroid Cancer Treatment Cooperative Study Group; NTCTCSG; bortezomib; velcade; metastatic differentiated thyroid carcinoma; Differentiated thyroid carcinoma; follicular epithelial thyroid cells; papillary; oxyphilic cell; Hurthle cell; insular cell; columnar cell; tall cell
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Thyroid Diseases; Thyroid Neoplasms; Thyroid Cancer, Papillary; Adenocarcinoma, Follicular; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: NCI-2009-00045; 2004-0059 (Other Identifier: UT MD Anderson Cancer Center); N01CM62202 (U.S. NIH Grant/Contract); N01CM62203 (U.S. NIH Grant/Contract); N01CM17003 (U.S. NIH Grant/Contract); CDR0000415376 (Registry Identifier: PDQ (Physician Data Query))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No