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Trial of Cabozantinib (XL184) in Non-Small Cell Lung Cancer With Brain Metastases

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ClinicalTrials.gov Identifier: NCT02132598
Recruitment Status : Terminated (Trial stopped due to slow patient accrual.)
First Posted : May 7, 2014
Results First Posted : September 16, 2020
Last Update Posted : March 10, 2021
Sponsor:
Collaborator:
Exelixis
Information provided by (Responsible Party):
Liza Villaruz, MD, University of Pittsburgh

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Non Small Cell Lung Cancer (NSCLC)
Metastases to the Brain
Intervention Drug: cabozantinib
Enrollment 5
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cabozantinib (XL184)
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Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Period Title: Overall Study
Started 5
Completed 5
Not Completed 0
Arm/Group Title Cabozantinib (XL184)
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Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 5 participants
62.6
(51.0 to 76.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
5
 100.0%
Male
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
5
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
c-MET amplification   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Negative
3
  60.0%
Positive
2
  40.0%
[1]
Measure Description: c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the MET gene. Over-expression of c-Met protein has been associated with poor prognosis in some solid tumors.
Histology  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
ADENOCARCINOMA IN SITU, NOS
1
  20.0%
ADENOCARCINOMA, NOS
2
  40.0%
NON-SMALL CELL CA
2
  40.0%
Stage of Disease   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Stage IV
5
 100.0%
Stage l-III
0
   0.0%
[1]
Measure Description:

Stage 0. Cancer in situ; the cancer is only located in the place of origin.

Stage I. Small tumor with no deep growth into surrounding tissues; no spread to the lymph nodes or other body parts.

Stage II and Stage III. Larger cancers or tumors that have grown more deeply into surrounding tissue and may have spread to lymph nodes (only).

Stage IV. Cancer has spread to other body organs (metastasis).

1.Primary Outcome
Title Overall Response
Hide Description The proportion of response-evaluable patients who achieve Complete Response (CR) or Partial Response (PR) as best response by RECIST v1.1 criteria. Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Patients evaluable for response: Received at least one dose of study drug, and, underwent at least one radiologic scan follow-up.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 4
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.25
(0.006 to .806)
2.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description Proportion of response-evaluable patients that experienced Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) as best response (RECIST v1.1 criteria) per the total study population criteria. Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Stable Disease (SD) is defined as, neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD).
Time Frame Up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
As no patients who received at least one dose of study drug and underwent at least one follow-up radiologic scan were able to be evaluated later than 15 weeks, this endpoint cannot be assessed.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Progression-free survival is the time measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression), whichever occurs first, with progression defined by RECIST v 1.1. Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only one patient was assessed as having disease progression.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: days
45
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description The length of time from the start of treatment that patients remain alive, until death from any cause.
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
"All patients" includes all 5 of the patients for whom survival data were available, regardless of c-MET status. "c-MET positive patients" (only) does not include patients for who c-MET status was not positive.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 5
Median (95% Confidence Interval)
Unit of Measure: months
All patients Number Analyzed 5 participants
4.07 [1] 
(3.09 to NA)
c-MET positive patients (only) Number Analyzed 2 participants
2.25 [1] 
(0.43 to NA)
[1]
Upper bound of 95% CI not reached
5.Secondary Outcome
Title Time to Progression (TTP)
Hide Description Time from initiation of study treatment to disease progression per RECIST v1.1, excluding death from causes unrelated to the disease. As defined by RECIST v 1.1. Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame Until disease progression; Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only one participant experienced disease progression.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: days
45
6.Secondary Outcome
Title Worst Grade of Adverse Events Reported
Hide Description

Worst Grade of Adverse Events Reported as assessed by the investigator. Severity/grade defined by the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Subjects monitored continuously for Adverse Events (AE's) throughout the study and for 30 days after the last dose of study treatment.

Time Frame From baseline up to 20 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that received at least one dose of study drug.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
0
   0.0%
Grade 2
0
   0.0%
Grade 3
4
  80.0%
Grade 4
0
   0.0%
Grade 5
1
  20.0%
7.Secondary Outcome
Title Worst Grade of AE at Least Possibly Related to Treatment Reported
Hide Description

Worst Grade of Adverse Events Reported as assessed by the investigator. Severity/grade defined by the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Subjects monitored continuously for Adverse Events (AE's) throughout the study and for 30 days after the last dose of study treatment.

Time Frame From baseline up to 20 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that received at least one dose of study drug.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
0
   0.0%
Grade 2
0
   0.0%
Grade 3
5
 100.0%
Grade 4
0
   0.0%
Grade 5
0
   0.0%
8.Secondary Outcome
Title Worst Grade of AE at Least Probably Related to Treatment Reported
Hide Description

Worst Grade of Adverse Events Reported as assessed by the investigator. Severity/grade defined by the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Subjects monitored continuously for Adverse Events (AE's) throughout the study and for 30 days after the last dose of study treatment.

Time Frame From baseline up to 20 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that received at least one dose of study drug.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 4
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
0
   0.0%
Grade 2
0
   0.0%
Grade 3
4
 100.0%
Grade 4
0
   0.0%
Grade 5
0
   0.0%
9.Secondary Outcome
Title Worst Grade of AE Definitely Related to Treatment Reported:
Hide Description

Worst Grade of Adverse Events Reported as assessed by the investigator. Severity/grade defined by the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Subjects monitored continuously for Adverse Events (AE's) throughout the study and for 30 days after the last dose of study treatment.

Time Frame From baseline up to 20 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that received at least one dose of study drug.
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description:

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Overall Number of Participants Analyzed 1
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
0
   0.0%
Grade 2
0
   0.0%
Grade 3
1
 100.0%
Grade 4
0
   0.0%
Grade 5
0
   0.0%
Time Frame Up to 30 days after discontinuation of treatment.
Adverse Event Reporting Description Serious Adverse Events are defined as grade 3 and higher toxicity events, per CTCAE v4.0
 
Arm/Group Title Cabozantinib (XL184)
Hide Arm/Group Description

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

All-Cause Mortality
Cabozantinib (XL184)
Affected / at Risk (%)
Total   4/5 (80.00%) 
Hide Serious Adverse Events
Cabozantinib (XL184)
Affected / at Risk (%)
Total   5/5 (100.00%) 
General disorders   
Fatigue  1  2/5 (40.00%) 
Infections and infestations   
Infections and infestations - Other, specify  1  1/5 (20.00%) 
Urinary tract infection  1  1/5 (20.00%) 
Investigations   
Alkaline phosphatase increased  1  1/5 (20.00%) 
Blood bilirubin increased  1  2/5 (40.00%) 
GGT increased  1  1/5 (20.00%) 
Lymphocyte count decreased  1  1/5 (20.00%) 
Platelet count decreased  1  1/5 (20.00%) 
Metabolism and nutrition disorders   
Anorexia  1  1/5 (20.00%) 
Dehydration  1  1/5 (20.00%) 
Hyponatremia  1  1/5 (20.00%) 
Psychiatric disorders   
Confusion  1  1/5 (20.00%) 
Renal and urinary disorders   
Proteinuria  1  1/5 (20.00%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/5 (20.00%) 
Vascular disorders   
Hypertension  1  2/5 (40.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cabozantinib (XL184)
Affected / at Risk (%)
Total   5/5 (100.00%) 
Blood and lymphatic system disorders   
Anemia  1  1/5 (20.00%) 
Blood and lymphatic system disorders - Other, specify  1  1/5 (20.00%) 
Cardiac disorders   
Cardiac disorders - Other, specify  1  1/5 (20.00%) 
Sinus tachycardia  1  2/5 (40.00%) 
Endocrine disorders   
Hypothyroidism  1  1/5 (20.00%) 
Gastrointestinal disorders   
Abdominal pain  1  1/5 (20.00%) 
Constipation  1  2/5 (40.00%) 
Diarrhea  1  3/5 (60.00%) 
Dyspepsia  1  1/5 (20.00%) 
Dysphagia  1  1/5 (20.00%) 
Nausea  1  1/5 (20.00%) 
Vomiting  1  1/5 (20.00%) 
General disorders   
Chills  1  1/5 (20.00%) 
Edema limbs  1  1/5 (20.00%) 
Fatigue  1  5/5 (100.00%) 
Fever  1  1/5 (20.00%) 
Gait disturbance  1  1/5 (20.00%) 
General disorders and administration site conditions - Other, specify  1  1/5 (20.00%) 
Pain  1  1/5 (20.00%) 
Infections and infestations   
Infections and infestations - Other, specify  1  1/5 (20.00%) 
Urinary tract infection  1  1/5 (20.00%) 
Injury, poisoning and procedural complications   
Fracture  1  1/5 (20.00%) 
Investigations   
Activated partial thromboplastin time prolonged  1  1/5 (20.00%) 
Alanine aminotransferase increased  1  2/5 (40.00%) 
Alkaline phosphatase increased  1  2/5 (40.00%) 
Aspartate aminotransferase increased  1  3/5 (60.00%) 
Blood bilirubin increased  1  3/5 (60.00%) 
GGT increased  1  1/5 (20.00%) 
Investigations - Other, specify  1  2/5 (40.00%) 
Lipase increased  1  1/5 (20.00%) 
Lymphocyte count decreased  1  1/5 (20.00%) 
Platelet count decreased  1  2/5 (40.00%) 
Serum amylase increased  1  2/5 (40.00%) 
White blood cell decreased  1  1/5 (20.00%) 
Metabolism and nutrition disorders   
Anorexia  1  1/5 (20.00%) 
Dehydration  1  1/5 (20.00%) 
Hypercalcemia  1  2/5 (40.00%) 
Hyperkalemia  1  1/5 (20.00%) 
Hypoalbuminemia  1  3/5 (60.00%) 
Hypocalcemia  1  1/5 (20.00%) 
Hypokalemia  1  2/5 (40.00%) 
Hypomagnesemia  1  4/5 (80.00%) 
Hyponatremia  1  3/5 (60.00%) 
Hypophosphatemia  1  1/5 (20.00%) 
Metabolism and nutrition disorders - Other, specify  1  3/5 (60.00%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/5 (20.00%) 
Generalized muscle weakness  1  1/5 (20.00%) 
Neck pain  1  1/5 (20.00%) 
Pain in extremity  1  1/5 (20.00%) 
Nervous system disorders   
Dizziness  1  1/5 (20.00%) 
Dysgeusia  1  1/5 (20.00%) 
Headache  1  2/5 (40.00%) 
Ischemia cerebrovascular  1  1/5 (20.00%) 
Peripheral sensory neuropathy  1  1/5 (20.00%) 
Psychiatric disorders   
Confusion  1  1/5 (20.00%) 
Renal and urinary disorders   
Proteinuria  1  1/5 (20.00%) 
Urine discoloration  1  1/5 (20.00%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/5 (40.00%) 
Dyspnea  1  1/5 (20.00%) 
Epistaxis  1  1/5 (20.00%) 
Respiratory, thoracic and mediastinal disorders - Other, specify  1  1/5 (20.00%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  1/5 (20.00%) 
Vascular disorders   
Hypertension  1  2/5 (40.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
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: Barbara Stadterman, MPH MCCR
Organization: UPMC Hillman Cancer Center
Phone: 412-647-5554
EMail: stadtermanbm@upmc.edu
Layout table for additonal information
Responsible Party: Liza Villaruz, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02132598    
Other Study ID Numbers: 13-182
First Submitted: April 30, 2014
First Posted: May 7, 2014
Results First Submitted: August 10, 2020
Results First Posted: September 16, 2020
Last Update Posted: March 10, 2021