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

NCT01025453 | Completed Phase 2 Results

• 1 other identifier: 09-148
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 5

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.

Conditions

Thyroid Cancer

Keywords

thyroid; follicular cell; papillary cell; Hurthle cell; BAY 43-9006; Temsirolimus; Sorafenib; 09-148

Outcome Measures

Primary Outcomes (1)

• 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

  2 years

Secondary Outcomes (3)

• Duration of Study Treatment for Participants With and Without BRAF Mutations

  6 years

• Percentage of Participants With Progression-free Survival Under the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.

  1 year

• Safety and Tolerability for the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.

  3 years

Study Arms (1)

Pts getting Temsirolimus and Sorafenib

EXPERIMENTAL

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.

Drug: Temsirolimus and Sorafenib

Interventions

Temsirolimus and Sorafenib DRUG

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.

Pts getting Temsirolimus and Sorafenib

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Comprehensive Cancer Network: collaborator
• Pfizer: collaborator

Study Sites (5)

Memorial Sloan-Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan-Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan-Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center

Sleepy Hollow, New York, 10591, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Thyroid Neoplasms; Thyroid Diseases

Interventions

temsirolimus; Sorafenib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Eric Sherman, MD
• Organization: Memorial Sloan Kettering Cancer Center

shermane@mskcc.org

646-888-4234

Study Officials

• Eric Sherman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2009
• First Posted: December 3, 2009
• Study Start: December 1, 2009
• Primary Completion: January 16, 2018
• Study Completion: January 16, 2018
• Last Updated: August 15, 2018
• Results First Posted: August 15, 2018

Record last verified: 2018-07

Locations

US (5)