Phase II Study Evaluating the Combination of Temsirolimus and Sorafenib in the Treatment of Radioactive Iodine Refractory Thyroid Cancer
Overview
- Phase
- Phase 2
- Intervention
- Temsirolimus and Sorafenib
- Conditions
- Thyroid Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 37
- Locations
- 5
- Primary Endpoint
- Reponse Rate of the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
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
- •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).
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
Arms & Interventions
Pts getting Temsirolimus and Sorafenib
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: Temsirolimus and Sorafenib
Outcomes
Primary Outcomes
Reponse Rate of the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Time Frame: 2 years
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 Outcomes
- 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)