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
Conditions
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
Brief summary
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
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.
Interventions
DRUGBortezomib
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).
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Rate Assessed by RECIST | Baseline to 12 weeks | 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. |
| Participant Tumor Response Assessed by RECIST | Baseline to 12 weeks (minimum of 4 treatment cycles (or 12 weeks)) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Assessed by RECIST | At 6 months | 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 |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: December 2004 to April 2010. Recruitment done in medical clinics.
Pre-assignment details
Of the 24 participants enrolled, two participants were not eligible and excluded from the study.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not evaluable | 1 |
Baseline characteristics
| Characteristic | Bortezomib |
|---|---|
| Age, Continuous | 62 years |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 17 / 22 |
Outcome results
Primary
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.
Time frame: Baseline to 12 weeks
Population: Two participants were not evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bortezomib | Objective Tumor Response Rate Assessed by RECIST | 0 participants |
Primary
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.
Time frame: Baseline to 12 weeks (minimum of 4 treatment cycles (or 12 weeks))
Population: Two participants were not evaluable for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Participant Tumor Response Assessed by RECIST | Complete Response | 0 participants |
| Bortezomib | Participant Tumor Response Assessed by RECIST | Partial Response | 0 participants |
| Bortezomib | Participant Tumor Response Assessed by RECIST | Stable Disease | 11 participants |
| Bortezomib | Participant Tumor Response Assessed by RECIST | Progressive Disease | 9 participants |
Secondary
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
Time frame: At 6 months
Population: Two participants were not evaluable for response.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bortezomib | Progression-free Survival Assessed by RECIST | 4 Participants |