Clinical Trial: Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: Phase II Study of Cabozantinib in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer Who Progressed on Prior VEGFR-Targeted Therapy

Brief Summary: 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.

Detailed Summary:

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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).

TERTIARY OBJECTIVES:

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 thyro
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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 ]

Original Primary Outcome: Objective response rate, defined as the proportion of patients who have had a PR or CR as assessed by the RECIST v1.1 [ Time Frame: Up to 6 months ]

Current Secondary Outcome:

• Bone turnover, as measured by serum and urinary markers of bone turnover [ Time Frame: Up to 2 months ]
• 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 ]
  Evaluated using the methods of Kaplan and Meier.
• Expression levels of predictive biomarkers of response by immunohistochemistry in archived tumor tissue [ Time Frame: Baseline ]
  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.
• Genotype of biomarkers potentially predictive of response [ Time Frame: Baseline ]
  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.
• Incidence of severe (grade 3+) adverse events, graded according to the National Cancer Institute CTCAE v4.0 [ Time Frame: Up to 1 year ]
  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.
• Overall survival [ Time Frame: Time from start of treatment to time of death, assessed up to 1 year ]
  The Kaplan-Meier method will be used.
• Percent change in serum tumor marker thyroglobulin levels [ Time Frame: Baseline to 6 months ]
  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.
• Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year ]
  The Kaplan-Meier method will be used.
• 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 ]

Original Secondary Outcome:

• 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 ]
  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 ]
  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 ]
  The Kaplan-Meier method will be used.
• Incidence of severe (grade 3+) adverse events, graded according to the National Cancer Institute (NCI) CTCAE v4.0 [ Time Frame: Up to 1 year ]
  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 ]
  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 ]
• Bone turnover, as measured by serum and urinary markers of bone turnover [ Time Frame: Up to 2 months ]

Dates:
Date Received: March 12, 2013
Date Started: May 2013
Date Completion:
Last Updated: May 23, 2017
Last Verified: May 2017