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Combination of Temsirolimus and Sorafenib in the Treatment of Radioactive Iodine Refractory Thyroid Cancer

Primary Purpose

Thyroid Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Temsirolimus and Sorafenib
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thyroid Cancer focused on measuring thyroid, follicular cell, papillary cell, Hurthle cell, BAY 43-9006, Temsirolimus, Sorafenib, 09-148

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have histopathologically confirmed at MSKCC thyroid carcinoma of follicular cell origin (D-TC-FCO), which includes papillary, follicular, Hürthle cell histology, or anaplastic along with their respective variants.
  • Available pathology for RAF mutational testing (e.g., paraffin block or 5-10 unstained slides). It is not required that mutational testing be completed before starting the clinical study.
  • Patients must have surgically inoperable and/or recurrent/metastatic disease.
  • Patients must have a PET scan prior to the protocol start date and have at least one FDGavid lesion that has not been removed surgically or radiated (unless it has progressed by RECIST criteria after the completion of radiation therapy and is still FDG-avid). FDGavidity will be defined as any focus of increased FDG uptake greater than normal activity with SUV maximum levels greater than or equal to 3. PET scan can have been done at any time prior to the start of therapy, although it is recommended that it be done within 3 months prior to the start of therapy.
  • Patients must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan; performed ≤ 4 weeks of protocol start date.
  • Patients must have progressive disease defined by at least one of the following occurring during or after previous treatment (including RAI treatment):
  • The presence of new or progressive lesions on CT/MRI.
  • New lesions on bone scan or PET scan.
  • Rising thyroglobulin level (documented by a minimum of three consecutive rises, with an interval of > 1 week between each determination).
  • Prior RAI therapy is allowed if > 3 months prior to initiation of therapy on this protocol and evidence of progression (as defined above) has been documented in the interim. A diagnostic study using <10 mCi of RAI is not considered RAI therapy.
  • Patients may have received prior external beam radiation therapy to index lesions ≥ 4 weeks prior to initiation of therapy on this protocol if there has been documented progression by RECIST criteria. Prior external beam radiation therapy to the non-index lesions is allowed if ≥ 4 weeks prior to initiation of therapy on this protocol.
  • ECOG performance status ≤ 2 (or Karnofsky performance status ≥ 60%).
  • Patients must have normal organ and marrow function as defined below:
  • Absolute neutrophil count ≥1,500/mcL
  • Platelets ≥100,000/mcL
  • Total bilirubin ≤ 1.5 X institutional ULN
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN
  • Creatinine ≤ 1.5 X institutional ULN OR
  • Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above 1.5 X institutional ULN [in this circumstance, either of a measured level based on a 24 hour urine collection, or a calculated level using the Cockcroft and Gault equation: (140 - age in years) X (weight in kg) X (0.85 if female)/72 X serum Cr may be used].
  • International normalized ratio (INR) ≤ 1.5 (or in range INR, usually between 2 and 3, if patient is on a stable dose of therapeutic warfarin).
  • *ULN = upper limit of normal
  • **unless liver metastasis present in which AST/ALT should be < 5 x ULN.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Age 21 years old or older.

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents.
  • Patients with known history of active intraparenchymal brain metastasis within previous 3 months.
  • Serious or non-healing wound, ulcer, or bone fracture.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
  • Patients with a reported history of clinically active diverticulosis or diverticulitis in the prior 3 years.
  • Patients with clinically significant cardiovascular disease as defined by the following:
  • History of CVA within past 6 months
  • Myocardial infarction, CABG or unstable angina within past 6 months
  • New York Heart Association grade III or greater congestive heart failure or Canadian Cardiovascular Class grade III or greater angina within past 6 months (Appendices B&C) Clinically significant peripheral vascular disease within past 6 months
  • Pulmonary embolism, DVT, or other thromboembolic event within past 6 months
  • Uncontrolled coronary artery disease, angina, congestive heart failure, or ventricular arrhythmia requiring acute medical management within past 6 months
  • History of myocardial infarct, cerebrovascular accident, or transient ischemic event within the past 6 month
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • While the use of Angiotensin-Converting Enzyme (ACE) inhibitors is not absolutely excluded, efforts should be made to see if patients on ACE inhibitors can be taken off the medication or switched to another medication.
  • Pregnant women will be ineligible; breastfeeding should be discontinued if the mother is treated with study drugs.
  • The use of agents that inhibit or induce CYP3A metabolism is not strictly prohibited, but should be avoided if possible. Potential CYP3A inducing agents include carbamazepine, phenytoin, barbiturates, rifabutin, rifampicin, and St. John's Wort. Potential CYP3A inhibitors include protease inhibitors, antifungals, macrolide antibiotics, nefazodone, and selective serotonin inhibitors.

Sites / Locations

  • Memorial Sloan-Kettering at Basking Ridge
  • Memorial Sloan-Kettering Cancer Center @ Suffolk
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan-Kettering at Mercy Medical Center
  • Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pts getting Temsirolimus and Sorafenib

Arm Description

We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.

Outcomes

Primary Outcome Measures

Reponse Rate of the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures

Duration of Study Treatment for Participants With and Without BRAF Mutations
Percentage of Participants With Progression-free Survival Under the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
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
Safety and Tolerability for the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Participant toxicities evaluated by CTCAE version 4.0

Full Information

First Posted
December 2, 2009
Last Updated
July 18, 2018
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Comprehensive Cancer Network, Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01025453
Brief Title
Combination of Temsirolimus and Sorafenib in the Treatment of Radioactive Iodine Refractory Thyroid Cancer
Official Title
Phase II Study Evaluating the Combination of Temsirolimus and Sorafenib in the Treatment of Radioactive Iodine Refractory Thyroid Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
December 1, 2009 (Actual)
Primary Completion Date
January 16, 2018 (Actual)
Study Completion Date
January 16, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Comprehensive Cancer Network, Pfizer

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to find out what effects, good and/or bad, the combination of sorafenib and temsirolimus will have on thyroid cancer. Treatment guidelines from the National Comprehensive Cancer Network include sorafenib as a treatment option for thyroid cancer. Temsirolimus is an intravenous medication that is FDA approved for other type of cancers. In laboratory studies, the addition of temsirolimus to sorafenib works better than sorafenib alone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Cancer
Keywords
thyroid, follicular cell, papillary cell, Hurthle cell, BAY 43-9006, Temsirolimus, Sorafenib, 09-148

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pts getting Temsirolimus and Sorafenib
Arm Type
Experimental
Arm Description
We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.
Intervention Type
Drug
Intervention Name(s)
Temsirolimus and Sorafenib
Intervention Description
Treatment will be with sorafenib 200 mg orally twice a day and temsirolimus 25 mg intravenous weekly. A cycle will be equivalent to 4 weeks of treatment.
Primary Outcome Measure Information:
Title
Reponse Rate of the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Duration of Study Treatment for Participants With and Without BRAF Mutations
Time Frame
6 years
Title
Percentage of Participants With Progression-free Survival Under the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Description
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
1 year
Title
Safety and Tolerability for the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Description
Participant toxicities evaluated by CTCAE version 4.0
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histopathologically confirmed at MSKCC thyroid carcinoma of follicular cell origin (D-TC-FCO), which includes papillary, follicular, Hürthle cell histology, or anaplastic along with their respective variants. Available pathology for RAF mutational testing (e.g., paraffin block or 5-10 unstained slides). It is not required that mutational testing be completed before starting the clinical study. Patients must have surgically inoperable and/or recurrent/metastatic disease. Patients must have a PET scan prior to the protocol start date and have at least one FDGavid lesion that has not been removed surgically or radiated (unless it has progressed by RECIST criteria after the completion of radiation therapy and is still FDG-avid). FDGavidity will be defined as any focus of increased FDG uptake greater than normal activity with SUV maximum levels greater than or equal to 3. PET scan can have been done at any time prior to the start of therapy, although it is recommended that it be done within 3 months prior to the start of therapy. Patients must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan; performed ≤ 4 weeks of protocol start date. Patients must have progressive disease defined by at least one of the following occurring during or after previous treatment (including RAI treatment): The presence of new or progressive lesions on CT/MRI. New lesions on bone scan or PET scan. Rising thyroglobulin level (documented by a minimum of three consecutive rises, with an interval of > 1 week between each determination). Prior RAI therapy is allowed if > 3 months prior to initiation of therapy on this protocol and evidence of progression (as defined above) has been documented in the interim. A diagnostic study using <10 mCi of RAI is not considered RAI therapy. Patients may have received prior external beam radiation therapy to index lesions ≥ 4 weeks prior to initiation of therapy on this protocol if there has been documented progression by RECIST criteria. Prior external beam radiation therapy to the non-index lesions is allowed if ≥ 4 weeks prior to initiation of therapy on this protocol. ECOG performance status ≤ 2 (or Karnofsky performance status ≥ 60%). Patients must have normal organ and marrow function as defined below: Absolute neutrophil count ≥1,500/mcL Platelets ≥100,000/mcL Total bilirubin ≤ 1.5 X institutional ULN AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN Creatinine ≤ 1.5 X institutional ULN OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above 1.5 X institutional ULN [in this circumstance, either of a measured level based on a 24 hour urine collection, or a calculated level using the Cockcroft and Gault equation: (140 - age in years) X (weight in kg) X (0.85 if female)/72 X serum Cr may be used]. International normalized ratio (INR) ≤ 1.5 (or in range INR, usually between 2 and 3, if patient is on a stable dose of therapeutic warfarin). *ULN = upper limit of normal **unless liver metastasis present in which AST/ALT should be < 5 x ULN. Ability to understand and the willingness to sign a written informed consent document. Age 21 years old or older. Exclusion Criteria: Patients may not be receiving any other investigational agents. Patients with known history of active intraparenchymal brain metastasis within previous 3 months. Serious or non-healing wound, ulcer, or bone fracture. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment. Patients with a reported history of clinically active diverticulosis or diverticulitis in the prior 3 years. Patients with clinically significant cardiovascular disease as defined by the following: History of CVA within past 6 months Myocardial infarction, CABG or unstable angina within past 6 months New York Heart Association grade III or greater congestive heart failure or Canadian Cardiovascular Class grade III or greater angina within past 6 months (Appendices B&C) Clinically significant peripheral vascular disease within past 6 months Pulmonary embolism, DVT, or other thromboembolic event within past 6 months Uncontrolled coronary artery disease, angina, congestive heart failure, or ventricular arrhythmia requiring acute medical management within past 6 months History of myocardial infarct, cerebrovascular accident, or transient ischemic event within the past 6 month Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. While the use of Angiotensin-Converting Enzyme (ACE) inhibitors is not absolutely excluded, efforts should be made to see if patients on ACE inhibitors can be taken off the medication or switched to another medication. Pregnant women will be ineligible; breastfeeding should be discontinued if the mother is treated with study drugs. The use of agents that inhibit or induce CYP3A metabolism is not strictly prohibited, but should be avoided if possible. Potential CYP3A inducing agents include carbamazepine, phenytoin, barbiturates, rifabutin, rifampicin, and St. John's Wort. Potential CYP3A inhibitors include protease inhibitors, antifungals, macrolide antibiotics, nefazodone, and selective serotonin inhibitors.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Sherman, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering at Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center @ Suffolk
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan-Kettering at Mercy Medical Center
City
Rockville Centre
State/Province
New York
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
City
Sleepy Hollow
State/Province
New York
ZIP/Postal Code
10591
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Combination of Temsirolimus and Sorafenib in the Treatment of Radioactive Iodine Refractory Thyroid Cancer

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