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A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT01663272
Recruitment Status : Completed
First Posted : August 13, 2012
Results First Posted : September 19, 2018
Last Update Posted : September 19, 2018
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pancreatic Cancer
Interventions Drug: CABOZANTINIB
Drug: gemcitabine
Enrollment 12
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Dose Level -1 Dose Level 1 Dose Level 2
Hide Arm/Group Description

20 mg of cabozantinib PO daily administered days -7 until disease progression, intolerable adverse event(s) or patient choice.

800mg/m^2 of gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.

20 mg of cabozantinib PO daily administered days -7 until disease progression, intolerable adverse event(s) or patient choice.

1000mg/m^2 of gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.

40 mg of cabozantinib PO daily administered days -7 until disease progression, intolerable adverse event(s) or patient choice.

1000mg/m^2 of gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.

Period Title: Overall Study
Started 5 6 1
Completed 5 6 1
Not Completed 0 0 0
Arm/Group Title Cabozantinib With Gemcitabine
Hide Arm/Group Description Patients received daily oral cabozantinib, at 20mg or 40mg, administered days -7 until disease progression, intolerable adverse event(s) or patient choice AND Gemcitabine at 800mg/m^2 or 1000mg/m^2 administered intravenously on days 1, 8, and 15 every 28 days.
Overall Number of Baseline Participants 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 12 participants
60.5
(41 to 75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
6
  50.0%
Male
6
  50.0%
1.Primary Outcome
Title Maximum Tolerated Dose
Hide Description The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).
Time Frame 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cabozantinib With Gemcitabine
Hide Arm/Group Description:

The Study Treatment Period will consist of continued treatment during which time patients will receive cabozantinib and gemcitabine until either disease progression or the occurrence of unacceptable drug-related toxicity

Cabozantinib: Daily oral cabozantinib (20mg OR 40mg) administered days -7 until disease progression, intolerable adverse event(s) or patient choice.

Gemcitabine: Gemcitabine (800mg/m^2 OR 1000mg/m^2) administered intravenously on days 1, 8, and 15 every 28 days.

Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: mg
NA [1] 
[1]
The MTD could not be determined as too many patients experienced toxicity at all dose levels.
2.Secondary Outcome
Title Median Progression-free Survival (PFS)
Hide Description Progression-free survival (PFS, a secondary endpoint) will be calculated from day-7 of cycle 1 of study treatment, until documented disease progression or death. Patients removed from treatment for progression or other reasons will be followed for 30 days after their last dose.
Time Frame day-7 of cycle 1 until 30 days post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cabozantinib With Gemcitabine
Hide Arm/Group Description:

The Study Treatment Period will consist of continued treatment during which time patients will receive cabozantinib and gemcitabine until either disease progression or the occurrence of unacceptable drug-related toxicity

Cabozantinib: Daily oral cabozantinib (20mg OR 40mg) administered days -7 until disease progression, intolerable adverse event(s) or patient choice.

Gemcitabine: Gemcitabine (800mg/m^2 OR 1000mg/m^2) administered intravenously on days 1, 8, and 15 every 28 days.

Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: months
4.7
(1.4 to 9.7)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cabozantinib With Gemcitabine
Hide Arm/Group Description Adverse events were pooled for all treated patients and were not collected by dose level. Patients received daily oral cabozantinib, at 20mg or 40mg, administered days -7 until disease progression, intolerable adverse event(s) or patient choice AND Gemcitabine at 800mg/m^2 or 1000mg/m^2 administered intravenously on days 1, 8, and 15 every 28 days.
All-Cause Mortality
Cabozantinib With Gemcitabine
Affected / at Risk (%)
Total   1/12 (8.33%)    
Show Serious Adverse Events Hide Serious Adverse Events
Cabozantinib With Gemcitabine
Affected / at Risk (%) # Events
Total   4/12 (33.33%)    
Gastrointestinal disorders   
Gastrointestinal Fistula  1/12 (8.33%)  1
Bile Duct Stenosis  1/12 (8.33%)  1
General disorders   
Death, NOS  1/12 (8.33%)  1
Infections and infestations   
Flu Like Symptoms  1/12 (8.33%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cabozantinib With Gemcitabine
Affected / at Risk (%) # Events
Total   11/12 (91.67%)    
Blood and lymphatic system disorders   
Anemia  5/12 (41.67%)  10
Ear and labyrinth disorders   
Tinnitus  1/12 (8.33%)  1
Gastrointestinal disorders   
Abdominal distension  1/12 (8.33%)  1
Abdominal pain  7/12 (58.33%)  7
Anal hemorrhage  1/12 (8.33%)  2
Bloating  1/12 (8.33%)  1
Constipation  4/12 (33.33%)  4
Diarrhea  4/12 (33.33%)  7
Dyspepsia  1/12 (8.33%)  1
Mucositis oral  1/12 (8.33%)  1
Nausea  7/12 (58.33%)  9
Oral pain  1/12 (8.33%)  1
Rectal pain  1/12 (8.33%)  1
Vomiting  3/12 (25.00%)  5
General disorders   
Chills  3/12 (25.00%)  3
Edema limbs  2/12 (16.67%)  2
Fatigue  8/12 (66.67%)  11
Fever  3/12 (25.00%)  3
Localized edema  2/12 (16.67%)  2
Pain  2/12 (16.67%)  2
Infections and infestations   
Biliary tract infection  1/12 (8.33%)  1
Papulopustular rash  1/12 (8.33%)  1
Pharyngitis  1/12 (8.33%)  1
Sepsis  1/12 (8.33%)  1
Upper respiratory infection  1/12 (8.33%)  1
Investigations   
Alanine aminotransferase increased  11/12 (91.67%)  28
Alkaline phosphatase increased  7/12 (58.33%)  11
Aspartate aminotransferase increased  9/12 (75.00%)  16
Blood bilirubin increased  3/12 (25.00%)  8
Creatinine increased  2/12 (16.67%)  2
Lipase increased  1/12 (8.33%)  4
Lymphocyte count decreased  5/12 (41.67%)  9
Neutrophil count decreased  9/12 (75.00%)  21
Platelet count decreased  10/12 (83.33%)  24
Weight loss  1/12 (8.33%)  1
White blood cell decreased  10/12 (83.33%)  31
Metabolism and nutrition disorders   
Anorexia  4/12 (33.33%)  4
Hypercalcemia  1/12 (8.33%)  1
Hyperglycemia  4/12 (33.33%)  10
Hyperkalemia  3/12 (25.00%)  3
Hypernatremia  1/12 (8.33%)  1
Hypoalbuminemia  2/12 (16.67%)  6
Hypocalcemia  4/12 (33.33%)  9
Hypoglycemia  2/12 (16.67%)  3
Hypokalemia  3/12 (25.00%)  5
Hyponatremia  3/12 (25.00%)  3
Hypophosphatemia  6/12 (50.00%)  8
Musculoskeletal and connective tissue disorders   
Back pain  1/12 (8.33%)  1
Generalized muscle weakness  2/12 (16.67%)  2
Musculoskeletal and connective tissue disorder - Other  1/12 (8.33%)  1
Pain in extremity  1/12 (8.33%)  1
Nervous system disorders   
Dizziness  1/12 (8.33%)  1
Dysgeusia  1/12 (8.33%)  1
Headache  3/12 (25.00%)  3
Psychiatric disorders   
Anxiety  4/12 (33.33%)  4
Renal and urinary disorders   
Proteinuria  2/12 (16.67%)  3
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1/12 (8.33%)  1
Cough  1/12 (8.33%)  1
Dyspnea  2/12 (16.67%)  2
Epistaxis  1/12 (8.33%)  2
Hoarseness  1/12 (8.33%)  1
Nasal congestion  1/12 (8.33%)  1
Wheezing  1/12 (8.33%)  1
Skin and subcutaneous tissue disorders   
Alopecia  1/12 (8.33%)  1
Rash maculo-papular  1/12 (8.33%)  1
Skin and subcutaneous tissue disorders - Other  1/12 (8.33%)  1
Vascular disorders   
Hypertension  5/12 (41.67%)  5
Hypotension  1/12 (8.33%)  1
The MTD could not be determined as too many patients experienced toxicity.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Mark Zalupski, M.D.
Organization: University of Michigan Comprehensive Cancer Center
Phone: 734-647-8902
EMail: zalupski@med.umich.edu
Layout table for additonal information
Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT01663272     History of Changes
Other Study ID Numbers: UMCC 2011.105
HUM 62927 ( Other Identifier: University of Michigan IRBMED )
First Submitted: July 24, 2012
First Posted: August 13, 2012
Results First Submitted: May 18, 2017
Results First Posted: September 19, 2018
Last Update Posted: September 19, 2018