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Cabozantinib (XL-184) Monotherapy for Advanced Cholangiocarcinoma

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ClinicalTrials.gov Identifier: NCT01954745
Recruitment Status : Completed
First Posted : October 7, 2013
Results First Posted : February 3, 2017
Last Update Posted : February 3, 2017
Sponsor:
Collaborator:
Exelixis
Information provided by (Responsible Party):
Goyal, Lipika, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Bile Duct Cancer
Intrahepatic Cholangiocarcinoma
Cholangiocarcinoma of the Extrahepatic Bile Duct
Intervention Drug: Cabozantinib
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cabozantinib
Hide Arm/Group Description

Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

Cabozantinib: Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

Period Title: Overall Study
Started 19
Completed 0
Not Completed 19
Reason Not Completed
Radiological Progression             11
Clinical Progression             5
Adverse Event             2
Death             1
Arm/Group Title Cabozantinib
Hide Arm/Group Description

Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

Cabozantinib: Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
<=18 years
0
   0.0%
Between 18 and 65 years
5
  26.3%
>=65 years
14
  73.7%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 19 participants
67
(45 to 74)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
13
  68.4%
Male
6
  31.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants
19
1.Primary Outcome
Title Median Progression Free Survival (PFS)
Hide Description To evaluate the median progression free survival (PFS) of cabozantinib in patients with advanced cholangiocarcinoma after progression on 1 or 2 prior systemic therapies.
Time Frame 2 Years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles
Arm/Group Title Cabozantinib
Hide Arm/Group Description:

Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

Cabozantinib: Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: months
1.8
(1.6 to 5.4)
2.Secondary Outcome
Title Number of Patients With Adverse Events
Hide Description Evaluate the number of patients with advanced cholangiocarcinoma being treated with cabozantinib who have adverse events during treatment
Time Frame 2 Years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles
Arm/Group Title Cabozantinib
Hide Arm/Group Description:

Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

Cabozantinib: Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

Overall Number of Participants Analyzed 19
Measure Type: Number
Unit of Measure: participants
19
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description To evaluate the objective response rate (ORR) for patients with advanced cholangiocarcinoma receiving cabozantinib
Time Frame 2 Years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles
Arm/Group Title Cabozantinib
Hide Arm/Group Description:

Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

Cabozantinib: Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

Overall Number of Participants Analyzed 19
Measure Type: Number
Unit of Measure: percent
0
4.Secondary Outcome
Title Median Overall Survival (OS)
Hide Description To evaluate the median overall survival (OS) for patients with advanced cholangiocarcinoma receiving cabozantinib
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles
Arm/Group Title Cabozantinib
Hide Arm/Group Description:

Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

Cabozantinib: Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: months
5.2
(2.7 to 10.5)
Time Frame October 1, 2013 through February 12, 2015
Adverse Event Reporting Description The most common drug-related adverse events were fatigue, elevated AST, and thrombocytopenia. Serious adverse events included but were not limited to neutropenia, hyperbilirubinemia, epistaxis, bowel perforation, enterocutaneous fistula, and hypertension.
 
Arm/Group Title Cabozantinib
Hide Arm/Group Description

Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

Cabozantinib: Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

All-Cause Mortality
Cabozantinib
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cabozantinib
Affected / at Risk (%)
Total   17/19 (89.47%) 
Blood and lymphatic system disorders   
Neutropenia  1  1/19 (5.26%) 
Thrombocytopenia  1  1/19 (5.26%) 
Lymphopenia  1  2/19 (10.53%) 
Elevated AST  1  1/19 (5.26%) 
Elevated AST  1  4/19 (21.05%) 
Elevated Serum ALKP  1  2/19 (10.53%) 
Lipasemia  1  1/19 (5.26%) 
Hyponatremia  1  4/19 (21.05%) 
Hypophosphatemia  1  2/19 (10.53%) 
Cardiac disorders   
Hypertension  1  2/19 (10.53%) 
Gastrointestinal disorders   
Gastrointestinal perforation  1  1/19 (5.26%) 
Abdominal pain  1  1/19 (5.26%) 
Mucositis  1  1/19 (5.26%) 
Gastrointestinal Fistula  1  1/19 (5.26%) 
PPE  1  1/19 (5.26%) 
General disorders   
Fatigue  1  1/19 (5.26%) 
Epistaxis  1  1/19 (5.26%) 
Dizziness  1  1/19 (5.26%) 
Metabolism and nutrition disorders   
Hyperbilirubinemia  1  1/19 (5.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cabozantinib
Affected / at Risk (%)
Total   19/19 (100.00%) 
Blood and lymphatic system disorders   
Thrombocytopenia  1  12/19 (63.16%) 
Leukopenia  1  11/19 (57.89%) 
Anemia  1  8/19 (42.11%) 
Neutropenia  1  6/19 (31.58%) 
Elevated AST  1  12/19 (63.16%) 
Elevated ALKP  1  12/19 (63.16%) 
Hyperglycemia  1  13/19 (68.42%) 
Elevated ALT  1  11/19 (57.89%) 
Hyponatremia  1  8/19 (42.11%) 
Hypomagnesemia  1  7/19 (36.84%) 
Hyperbilirubinemia  1  3/19 (15.79%) 
Hypophosphatemia  1  2/19 (10.53%) 
Hypoalbuminemia  1  4/19 (21.05%) 
Hypokalemia  1  2/19 (10.53%) 
Hyperkalemia  1  2/19 (10.53%) 
Cardiac disorders   
Hypertension  1  5/19 (26.32%) 
Gastrointestinal disorders   
Abdominal pain  1  12/19 (63.16%) 
Nausea  1  8/19 (42.11%) 
Diarrhea  1  7/19 (36.84%) 
Mucositis  1  6/19 (31.58%) 
Constipation  1  6/19 (31.58%) 
Vomiting  1  4/19 (21.05%) 
Dyspepsia/Heartburn  1  4/19 (21.05%) 
Abdominal distension  1  4/19 (21.05%) 
Cough  1  2/19 (10.53%) 
General disorders   
Fatigue  1  16/19 (84.21%) 
Asthenia  1  4/19 (21.05%) 
Palmar Plantar Erythrodysesthesia  1  3/19 (15.79%) 
Pyrexia  1  3/19 (15.79%) 
Foot pain  1  2/19 (10.53%) 
Insomnia  1  2/19 (10.53%) 
Hyperhidrosis  1  2/19 (10.53%) 
Flatulence  1  2/19 (10.53%) 
Back Pain  1  2/19 (10.53%) 
Psychiatric d/o  1  2/19 (10.53%) 
Dizziness  1  1/19 (5.26%) 
Bleeding  1  2/19 (10.53%) 
Metabolism and nutrition disorders   
Anorexia  1  8/19 (42.11%) 
Hypothyroidism  1  7/19 (36.84%) 
Weight Loss  1  3/19 (15.79%) 
Nervous system disorders   
Peripheral Sensory Neuropathy  1  2/19 (10.53%) 
Peripheral Motor Neuropathy  1  2/19 (10.53%) 
Skin and subcutaneous tissue disorders   
Rash  1  4/19 (21.05%) 
Dry Skin  1  3/19 (15.79%) 
Vascular disorders   
Peripheral edema  1  2/19 (10.53%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
After 12 patients failed to be progression-free at 16 weeks, the study was terminated as it was determined that the criterion for proceeding to stage 2 could not be met. (i.e. 9 of 20 patients needed to be progression free at 4 months.)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Lipika Goyal
Organization: Massachusetts General Hospital Cancer Center
Phone: 617-724-4000
Responsible Party: Goyal, Lipika, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01954745     History of Changes
Other Study ID Numbers: 13-221
XL184-IST26 ( Other Identifier: Exelixis )
First Submitted: September 24, 2013
First Posted: October 7, 2013
Results First Submitted: December 12, 2016
Results First Posted: February 3, 2017
Last Update Posted: February 3, 2017