Trial Outcomes & Findings for Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer (NCT NCT01811212)
NCT ID: NCT01811212
Last Updated: 2018-04-03
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Up to 6 months
Results posted on
2018-04-03
Participant Flow
Between September 2013 and January 2015 patients were enrolled by ITOG investigators at six centers in the United States.
Participant milestones
| Measure |
Treatment (Cabozantinib-s-malate)
Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Cabozantinib-s-malate)
n=25 Participants
Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
25 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 6 monthsPer 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
Outcome measures
| Measure |
Treatment (Cabozantinib-s-malate)
n=25 Participants
Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
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
|
10 Participants
|
SECONDARY outcome
Timeframe: Up to 2 monthsPopulation: Data not collected to be analyzed at this time
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From date of documentation of response to the date of progression or death, assessed up to 1 yearProgression 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.
Outcome measures
| Measure |
Treatment (Cabozantinib-s-malate)
n=25 Participants
Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Duration of Objective Response as Assessed by the RECIST v1.1
|
11.3 months
Interval 10.3 to
not evaluable
|
SECONDARY outcome
Timeframe: BaselinePopulation: Data has not been collected and analyzed at this time
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: BaselinePopulation: Data not collected to be analyzed at this time
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 1 yearThe 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.
Outcome measures
| Measure |
Treatment (Cabozantinib-s-malate)
n=25 Participants
Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0
Left ventricular systolic dysfunction
|
1 Participants
|
|
Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0
osteonecrosis of the jaw
|
1 Participants
|
|
Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0
decubitus ulcer
|
1 Participants
|
|
Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0
pneumonia
|
1 Participants
|
|
Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0
meningitis
|
1 Participants
|
|
Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0
asymptomatic increased lipase
|
1 Participants
|
|
Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0
perianal hidradenitis suppurativa
|
1 Participants
|
SECONDARY outcome
Timeframe: Time from start of treatment to time of death, assessed up to 1 yearPopulation: the end of the range was not reached
The Kaplan-Meier method will be used.
Outcome measures
| Measure |
Treatment (Cabozantinib-s-malate)
n=25 Participants
Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Overall Survival
|
34.7 months
Interval 18.3 to
Not reached
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsPopulation: Data not collected to be analyzed at this time
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 yearThe Kaplan-Meier method will be used.
Outcome measures
| Measure |
Treatment (Cabozantinib-s-malate)
n=25 Participants
Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Progression-free Survival
|
12.7 months
Interval 10.9 to 34.7
|
SECONDARY outcome
Timeframe: Up to 2 monthsPopulation: Data not collected to be analyzed at this time
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Cabozantinib-s-malate)
Serious events: 7 serious events
Other events: 25 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Treatment (Cabozantinib-s-malate)
n=25 participants at risk
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.
Cabozantinib S-malate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Vascular disorders
Thrombotic
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Vascular disorders
Deep venous thrombosis
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Skin and subcutaneous tissue disorders
Perianal hidradenitis suppurativa
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Asymptomatic increased lipase
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Gastrointestinal disorders
Osteonecrosis of the jaw
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Skin and subcutaneous tissue disorders
decubitus ulcer
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Nervous system disorders
Meningitis
|
4.0%
1/25 • Number of events 1
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
Other adverse events
| Measure |
Treatment (Cabozantinib-s-malate)
n=25 participants at risk
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.
Cabozantinib S-malate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
General disorders
Fatigue
|
76.0%
19/25 • Number of events 19
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Anorexia
|
64.0%
16/25 • Number of events 16
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Investigations
Weight Loss
|
60.0%
15/25 • Number of events 15
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Nervous system disorders
Dysgeusia
|
48.0%
12/25 • Number of events 12
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Gastrointestinal disorders
Oral mucositis
|
56.0%
14/25 • Number of events 14
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Gastrointestinal disorders
Dry mouth
|
28.0%
7/25 • Number of events 7
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Gastrointestinal disorders
Nausea
|
64.0%
16/25 • Number of events 16
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Gastrointestinal disorders
Vomiting
|
28.0%
7/25 • Number of events 7
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Gastrointestinal disorders
Diarrhea
|
72.0%
18/25 • Number of events 18
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Gastrointestinal disorders
Other GI
|
40.0%
10/25 • Number of events 10
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia
|
76.0%
19/25 • Number of events 19
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.0%
4/25 • Number of events 4
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Skin and subcutaneous tissue disorders
Other dermatologic disorder
|
40.0%
10/25 • Number of events 10
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Vascular disorders
Hypertension
|
48.0%
12/25 • Number of events 12
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Vascular disorders
Proteninuria
|
32.0%
8/25 • Number of events 8
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Vascular disorders
Bleeding
|
24.0%
6/25 • Number of events 6
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Musculoskeletal and connective tissue disorders
Pain
|
32.0%
8/25 • Number of events 8
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Nervous system disorders
Headache
|
24.0%
6/25 • Number of events 6
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Musculoskeletal and connective tissue disorders
Other muscoskeletal
|
12.0%
3/25 • Number of events 3
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
40.0%
10/25 • Number of events 10
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Musculoskeletal and connective tissue disorders
Peripherial neuropathy
|
12.0%
3/25 • Number of events 3
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Liver transaminase elevation
|
80.0%
20/25 • Number of events 20
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
56.0%
14/25 • Number of events 14
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Lipase or amylase elevation
|
28.0%
7/25 • Number of events 7
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
48.0%
12/25 • Number of events 12
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
36.0%
9/25 • Number of events 9
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.0%
4/25 • Number of events 4
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
24.0%
6/25 • Number of events 6
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Alkaline phosphatase elevation
|
16.0%
4/25 • Number of events 4
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
12.0%
3/25 • Number of events 3
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
8.0%
2/25 • Number of events 2
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Blood and lymphatic system disorders
Amenia
|
36.0%
9/25 • Number of events 9
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
32.0%
8/25 • Number of events 8
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Blood and lymphatic system disorders
Leukopenia
|
28.0%
7/25 • Number of events 7
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.0%
4/25 • Number of events 4
The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.
|
Additional Information
Manisha Shah, MD
The Ohio State University Compreshive Cancer Center
Phone: 614-366-6994
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60