Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer
This phase II trial studies how well cabozantinib-s-malate works in treating patients with thyroid cancer that does not respond to treatment. Cabozantinib-s-malate may stop the growth of thyroid cancer by blocking some of the enzymes needed for cell growth. Cabozantinib-s-malate may also stop the growth of thyroid cancer by blocking blood flow to the tumor.
Insular Thyroid Cancer
Recurrent Thyroid Cancer
Stage I Follicular Thyroid Cancer
Stage I Papillary Thyroid Cancer
Stage II Follicular Thyroid Cancer
Stage II Papillary Thyroid Cancer
Stage III Follicular Thyroid Cancer
Stage III Papillary Thyroid Cancer
Stage IVA Follicular Thyroid Cancer
Stage IVA Papillary Thyroid Cancer
Stage IVB Follicular Thyroid Cancer
Stage IVB Papillary Thyroid Cancer
Stage IVC Follicular Thyroid Cancer
Stage IVC Papillary Thyroid Cancer
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Cabozantinib in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer Who Progressed on Prior VEGFR-Targeted Therapy|
- Objective response rate, defined as the proportion of patients who have had a PR or CR as assessed by the RECIST version (v)1.1 [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]Exact binomial 95% confidence intervals for the true PR+CR response rate will be calculated.
- Duration of objective response as assessed by the RECIST v1.1 [ Time Frame: From date of documentation of response to the date of progression or death, assessed up to 1 year ] [ Designated as safety issue: No ]Evaluated using the methods of Kaplan and Meier.
- Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year ] [ Designated as safety issue: No ]The Kaplan-Meier method will be used.
- Overall survival [ Time Frame: Time from start of treatment to time of death, assessed up to 1 year ] [ Designated as safety issue: No ]The Kaplan-Meier method will be used.
- Incidence of severe (grade 3+) adverse events, graded according to the National Cancer Institute CTCAE v4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Tolerability of the regimens will be assessed through assessing the number of patients who required dose modifications and/or dose delays. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be captured.
- Percent change in serum tumor marker thyroglobulin levels [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]Side-by-side boxplots will be used to assess possible differences in this change between responders and non-responders, and scatterplots can assess the influence of baseline thyroglobulin levels on these measures of change.
- Response of cabozantinib-s-malate in bone metastasis (bone metastasis-specific progression free survival) as evaluated by functional imaging [ Time Frame: Up to 2 months ] [ Designated as safety issue: No ]
- Bone turnover, as measured by serum and urinary markers of bone turnover [ Time Frame: Up to 2 months ] [ Designated as safety issue: No ]
- Genotype of biomarkers potentially predictive of response [ Time Frame: Baseline ] [ Designated as safety issue: No ]These baseline levels will be quantitatively summarized and graphically explored, in particular in terms of how they relate to clinical outcomes of interest. Analyses exploring differences in these angiogenic and correlative markers in relation to clinical outcomes will be largely hypothesis-generating. With limited numbers of patients patterns of difference will primarily be looked for using graphical analyses; these can include plots of these marker levels in relation to clinical outcomes to identify potential patterns of interest.
- Expression levels of predictive biomarkers of response by immunohistochemistry in archived tumor tissue [ Time Frame: Baseline ] [ Designated as safety issue: No ]These baseline levels will be quantitatively summarized and graphically explored, in particular in terms of how they relate to clinical outcomes of interest. Analyses exploring differences in these angiogenic and correlative markers in relation to clinical outcomes will be largely hypothesis-generating. With limited numbers of patients patterns of difference will primarily be looked for using graphical analyses; these can include plots of these marker levels in relation to clinical outcomes to identify potential patterns of interest.
|Study Start Date:||May 2013|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cabozantinib-s-malate)
Patients receive cabozantinib-s-malate PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: laboratory biomarker analysis
I. The objective response rate, defined as the proportion of patients who have had a partial response (PR) or complete response (CR) within the first 6 months after initiation of therapy with cabozantinib (cabozantinib-s-malate).
I. To assess duration of objective response, progression-free survival and overall survival.
II. To assess tolerability and adverse events of cabozantinib as a 2nd line therapy in patients with differentiated thyroid cancer (DTC).
I. To assess effect of cabozantinib on serum tumor marker thyroglobulin and its correlation with overall response rate.
II. To assess response of cabozantinib in bone metastasis (bone metastasis-specific progression free survival) as evaluated by pre- and on-study functional imaging such as bone scan, fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET) scan and/or 18F sodium fluoride (NaF) PET scan.
III. To assess effect of cabozantinib on serum and urinary markers of bone turnover and its correlation with response to bone metastasis.
IV. To assess predictors of response by performing tumor genotype studies (e.g. v-raf murine sarcoma viral oncogene homolog B [BRAF], rat sarcoma [RAS], phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [PIK3CA], mitogen-activated protein kinase 1 [MAP2K1], v-akt murine thymoma viral oncogene homolog 1 [AKT1], mesenchymal-epithelial transition [MET], rearranged in transformation [RET]/papillary thyroid carcinoma [PTC] rearrangement) in archived tumor tissue.
V. To assess predictors of response by assessing baseline expression levels of vascular endothelial growth factor (VEGF), phosphorylated vascular endothelial growth factor receptor (pVEGFR), phosphorylated mitogen-activated protein kinase 1 (pERK), phosphorylated AKT1 (pAKT) and/or total met proto-oncogene (MET) by immunohistochemistry in archived tumor tissue.
Patients receive cabozantinib-s-malate orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks and then every 3 months for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01811212
|United States, District of Columbia|
|Lombardi Comprehensive Cancer Center at Georgetown University||Recruiting|
|Washington, District of Columbia, United States, 20057|
|Contact: Stephen V. Liu 202-444-3958 Stephen.V.Liu@gunet.georgoetown.edu|
|Principal Investigator: Stephen V. Liu|
|United States, Florida|
|Mayo Clinic in Florida||Recruiting|
|Jacksonville, Florida, United States, 32224-9980|
|Contact: Robert C. Smallridge 904-953-2224 firstname.lastname@example.org|
|Principal Investigator: Robert C. Smallridge|
|United States, Illinois|
|University of Chicago||Recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Jonas De Souza 773-834-1736 email@example.com|
|Principal Investigator: Jonas De Souza|
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Lori J. Wirth 617-726-0250 LWIRTH@PARTNERS.ORG|
|Principal Investigator: Lori J. Wirth|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Keith C. Bible 507-266-0029 firstname.lastname@example.org|
|Principal Investigator: Keith C. Bible|
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Yujie Zhao 716-845-8568 Yujie.Zhao@RoswellPark.org|
|Principal Investigator: Yujie Zhao|
|United States, Ohio|
|Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Manisha H. Shah 614-293-4680 email@example.com|
|Principal Investigator: Manisha H. Shah|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Maria E. Cabanillas 713-563-0764 firstname.lastname@example.org|
|Principal Investigator: Maria E. Cabanillas|
|Principal Investigator:||Manisha Shah||Ohio State University|