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Study Summary
No. 2008-0564:.......Thyroid......Steven I. Sherman......Endocrine Neoplasia & Hormonal Disorders
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Study Summary Title
Study Summary
Number:
2008-0564
Study Title:Phase II, Multicenter, Open-label, Single Arm Trial to Evaluate the Safety and Efficacy of Oral E7080 in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology
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Physician New Patient Referral
Name:Steven I. ShermanPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Endocrine Neoplasia & Hormonal DisordersReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2841
Contact us about clinical trials
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General Information
Disease Group:ThyroidSupported By:Eisai Medical Research, Inc.
Phase of Study:Phase IIReturn
Visit:
After Cycles 1 and 2, unless The patient had severe side effects, the visits
will convert to once a month.
If you have had serious side effects Cycle 3 will require more frequent visits
Treatment
Agents:
E7080Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
There are no anticipated hospitalization with this study
Description/
Intervention:
The goal of this clinical research study is to learn if E7080 can help to
control metastatic thyroid cancer. The safety of this drug will also be
studied.
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Study Objectives / Outcomes
Primary Objective:
    In patients with medullary thyroid cancer [MTC] or radioiodine (131 I) refractory / resistant differentiated thyroid cancer[DTC]:
    a.) Determine the effect of E7080 on the objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) by independent imaging review (IIR)
    b) Determine the pharmacokinetic (PK) profile and the pharmacokinetic/pharmacodynamic (PK/PD) relationships of E7080

    Secondary Objectives:

    1. Determine the effect of E7080 on duration of response by (Independant Imaging Review) IIR (Independant Imaging Review)
    2. Measure the effect of E7080 on the disease control rate (DCR) and clinical benefit rate (CBR) by IIR
    3. Determine the time to response by IIR
    4. Evaluate the effect of E7080 on progression free survival (PFS) by IIR and overall survival (OS)
    5. Evaluate the safety and tolerability of E7080
    6. Assess the influence of DNA sequence variants on metabolic enzymes and
transporters possibly involved in variability of E7080 PK parameters by genotyping
patient's genomic DNA using the Affymetrix DMET™ array
    7. Determine the biochemical response using tumor markers (either thyroglobulin for patients with DTC / calcitonin & carcinoembryonic antigen [CEA] for patients with MTC)
    8. Investigate the potential correlation of the following biomarkers with efficacy:
    • Serum proteome expression
    • Serum biomarkers for monitoring markers of apoptosis (CASP 3/7, Cytochrome C and M-30 neoantigen)
    9. Assess the effect of somatic DNA sequence variants in BRAF, H-, K- and N-Ras and RET/PTC1, 2 and 3 and germline DNA sequence variants in RET and near FOXE1 (rs965513) and NKX2-1 (rs944289) on patient response to study treatment
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:10/15/2009
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:104 (Stage I will require 16 patients per stratum. Stage II will require 36 additional patients per stratum)
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients must have histologically or cytologically confirmed diagnosis of one of the following: A. DTC, including any of the following subtypes: a. Papillary thyroid cancer (PTC): Follicular variant, Variants (including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hürthle cell variant of papillary carcinoma, poorly differentiated). b. Follicular thyroid cancer (FTC): Hürthle cell, Clear cell, Insular. B. MTC.

2) Measurable disease meeting the following criterion: a. At least one lesion (=>1.5 cm in longest diameter for non-lymph nodes and =>2.0 cm in longest diameter for lymph nodes) which is serially and accurately measurable according to Modified RECIST using either CT/MRI. b. Lesions that have had EBRT must show evidence of progressive disease based on Modified RECIST to be deemed a target lesion.

3) Patients must show evidence of disease progression by RECIST using site assessment of CT/MRI scans within 12 months (+1 month to allow for variances in patient scanning intervals) prior to study entry.

4) Patients with DTC must be 131I refractory/resistant as defined by at least one of the following:a. One or more measurable lesions that have never demonstrated 131I uptake on any radioiodine scan based on either collected scans or reports, b. One or more measurable lesions with disease progression by RECIST within 12 months (+1 month to allow for variances in patient scanning intervals) of 131I therapy despite 131I uptake on radioiodine scan based on site assessment of CT/MRI scans.

5) Patients with DTC must be 131I refractory/resistant as defined by at least one of the following:c. Cumulative activity of 131I of >600 mCi or 22 gigabequerels (GBq), with the last dose administered at least 6 months prior to study entry.

6) Patients must have unresectable disease. Patients must not be amenable to surgery.

7) Patients with DTC must be receiving thyroxine suppression therapy and TSH should not be elevated (TSH should be <= 5.50 mcu/mL) (revised per Amendment 01). When tolerated by the patient, thyroxine dose should be changed to achieve TSH suppression (TSH < 0.50 mcu/mL) and this dose can be changed concurrently upon starting E7080.

8) Patients must not have had chemotherapy, major surgery, monoclonal antibody therapy or experimental therapy within the 30 days prior to the start of E7080 (6 weeks for nitrosoureas or mitomycin C). Prior exposure to receptor tyrosine kinase inhibitors and antiangiogenic agents (including but not limited to AEE788, AG-013736, AMG706, AZD2171, bevacizumab, CP-547,632, dasatinib, enzataurin, imatinib mesylate, lenalidomide, pazopanib, sorafenib, sunitinib, thalidomide, vatalanib, VEGF Trap, and ZD6474) is allowed with at least 30 days between this therapy and the start of E7080 treatment.

9) All chemotherapy or radiation-related toxicities must have resolved to < Grade 2 severity, except alopecia and infertility.

10) Prior thyroidectomy is allowed.

11) Blood pressure should be well controlled (<= 140/90 mm Hg at Pre-Treatment) with or without antihypertensive medications.

12) Patients must be aged => 18 years.

13) Patients must have an ECOG Performance Status of 0 to 2.

14) Patients must have signed a written informed consent prior to any study specific Pre- Treatment procedures with the understanding that the patient may withdraw consent at any time without prejudice.

15) Patients must be willing and able to comply with the protocol guidelines for the duration of the study.

Exclusion Criteria:1) Anaplastic thyroid carcinoma, thyroid lymphoma, mesenchymal tumors of the thyroid, metastases to the thyroid

2) Any of the following laboratory measurements: A. hemoglobin < 9 g/dL (5.6 mmol/L) (may be corrected with growth factor or transfusions); B. neutrophils < 1.5 x 10^9/L; platelets < 100 x 10^9/L

3) "'continued" C. bilirubin > 1.5 times the upper limit of normal and other liver function tests (AST, ALT & alkaline phosphatase) with values greater than three times ULN; (in the case of liver metastases > five times ULN). If alkaline phosphatase is greater than three times the ULN (in the absence of liver metastasis) or greater than five times the ULN (in the presence of liver metastasis), & the patient is known to have bone metastasis, the liver specific alkaline phosphatase must be separated from total & liver specific alkaline phosphatase alone should be used to assess liver function .

4) "continued" D. renal function with serum creatinine > 1.5 ULN and/or creatinine clearance < 60 mL/min per the Cockcroft and Gault formula

5) Significant cardiovascular impairment (history of congestive heart failure > NYHA Class II, unstable angina or myocardial infarction within 6 months of study start, or serious cardiac arrhythmia)

6) Active hemoptysis (bright red blood of at least ½ teaspoon) in the 28 days prior to study entry

7) Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, with a therapeutic international normalized ratio (INR)

8) Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection

9) Organ allografts requiring immunosuppressive treatment

10) Prior malignancy, other than non-melanoma skin cancer or cervical carcinoma in situ, unless the prior malignancy was diagnosed and definitively treated >/ = 5 years previously with no subsequent evidence of recurrence

11) Brain or leptomeningeal (central nervous system [CNS]) metastases. Patients with stable or previously irradiated brain metastases are also excluded.

12) Marked baseline prolongation of QT/QTc interval (QTc interval > / = 500 msec) using the Fridericia method (QTc = QT/RR^0.33) for QTc analysis

13) > 1+ proteinuria on urine dipstick testing or >30 mg/dL

14) History of gastrointestinal malabsorption or having undergone surgery requiring gastrointestinal anastomoses within 4 weeks of starting therapy or who have not recovered from major surgery within 4 weeks of starting therapy

15) Women who are pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at Pre-Treatment or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (including two forms of contraception, one of which must be a barrier method) in the opinion of the investigator.

16) Perimenopausal women must be amenorrheic for at least 12 months to be considered of non childbearing potential. Fertile males with female partners who are not willing to use contraception or whose female partners are not using adequate contraceptive protection are excluded.

17) Other significant disease or disorder that, in the investigator's opinion, would exclude the patient from the study

18) Previous E7080 therapy

19) Previous treatment with an investigational drug, with the exception of those identified in inclusion criteria 8, within the 30 days prior to the start of E7080 administration

20) History of alcoholism, drug addiction, psychiatric or psychological condition, or social situation which, in the opinion of the investigator, would impair study compliance

21) Legal incapacity

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Links
Registration Number: NCT00784303
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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