Trial Outcomes & Findings for A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer (NCT NCT01663272)
NCT ID: NCT01663272
Last Updated: 2018-09-19
Results Overview
The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
5 weeks
Results posted on
2018-09-19
Participant Flow
Participant milestones
| Measure |
Dose Level -1
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.
|
Dose Level 1
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.
|
Dose Level 2
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
5
|
6
|
1
|
|
Overall Study
COMPLETED
|
5
|
6
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer
Baseline characteristics by cohort
| Measure |
Cabozantinib With Gemcitabine
n=12 Participants
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.
|
|---|---|
|
Age, Continuous
|
60.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 5 weeksThe MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).
Outcome measures
| Measure |
Cabozantinib With Gemcitabine
n=12 Participants
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.
|
|---|---|
|
Maximum Tolerated Dose
|
NA mg
The MTD could not be determined as too many patients experienced toxicity at all dose levels.
|
SECONDARY outcome
Timeframe: day-7 of cycle 1 until 30 days post treatmentProgression-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.
Outcome measures
| Measure |
Cabozantinib With Gemcitabine
n=12 Participants
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.
|
|---|---|
|
Median Progression-free Survival (PFS)
|
4.7 months
Interval 1.4 to 9.7
|
Adverse Events
Cabozantinib With Gemcitabine
Serious events: 4 serious events
Other events: 11 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Cabozantinib With Gemcitabine
n=12 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Gastrointestinal Fistula
|
8.3%
1/12 • Number of events 1
|
|
General disorders
Death, NOS
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Flu Like Symptoms
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Bile Duct Stenosis
|
8.3%
1/12 • Number of events 1
|
Other adverse events
| Measure |
Cabozantinib With Gemcitabine
n=12 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
41.7%
5/12 • Number of events 10
|
|
Ear and labyrinth disorders
Tinnitus
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
58.3%
7/12 • Number of events 7
|
|
Gastrointestinal disorders
Anal hemorrhage
|
8.3%
1/12 • Number of events 2
|
|
Gastrointestinal disorders
Bloating
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
33.3%
4/12 • Number of events 4
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
4/12 • Number of events 7
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
58.3%
7/12 • Number of events 9
|
|
Gastrointestinal disorders
Oral pain
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Rectal pain
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
3/12 • Number of events 5
|
|
General disorders
Chills
|
25.0%
3/12 • Number of events 3
|
|
General disorders
Edema limbs
|
16.7%
2/12 • Number of events 2
|
|
General disorders
Fatigue
|
66.7%
8/12 • Number of events 11
|
|
General disorders
Fever
|
25.0%
3/12 • Number of events 3
|
|
General disorders
Localized edema
|
16.7%
2/12 • Number of events 2
|
|
General disorders
Pain
|
16.7%
2/12 • Number of events 2
|
|
Infections and infestations
Biliary tract infection
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Papulopustular rash
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Pharyngitis
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Sepsis
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
91.7%
11/12 • Number of events 28
|
|
Investigations
Alkaline phosphatase increased
|
58.3%
7/12 • Number of events 11
|
|
Investigations
Aspartate aminotransferase increased
|
75.0%
9/12 • Number of events 16
|
|
Investigations
Blood bilirubin increased
|
25.0%
3/12 • Number of events 8
|
|
Investigations
Creatinine increased
|
16.7%
2/12 • Number of events 2
|
|
Investigations
Lipase increased
|
8.3%
1/12 • Number of events 4
|
|
Investigations
Lymphocyte count decreased
|
41.7%
5/12 • Number of events 9
|
|
Investigations
Neutrophil count decreased
|
75.0%
9/12 • Number of events 21
|
|
Investigations
Platelet count decreased
|
83.3%
10/12 • Number of events 24
|
|
Investigations
Weight loss
|
8.3%
1/12 • Number of events 1
|
|
Investigations
White blood cell decreased
|
83.3%
10/12 • Number of events 31
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
4/12 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
33.3%
4/12 • Number of events 10
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
25.0%
3/12 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypernatremia
|
8.3%
1/12 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
16.7%
2/12 • Number of events 6
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
33.3%
4/12 • Number of events 9
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
16.7%
2/12 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypokalemia
|
25.0%
3/12 • Number of events 5
|
|
Metabolism and nutrition disorders
Hyponatremia
|
25.0%
3/12 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
50.0%
6/12 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
16.7%
2/12 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Headache
|
25.0%
3/12 • Number of events 3
|
|
Psychiatric disorders
Anxiety
|
33.3%
4/12 • Number of events 4
|
|
Renal and urinary disorders
Proteinuria
|
16.7%
2/12 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
16.7%
2/12 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.3%
1/12 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
8.3%
1/12 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
8.3%
1/12 • Number of events 1
|
|
Vascular disorders
Hypertension
|
41.7%
5/12 • Number of events 5
|
|
Vascular disorders
Hypotension
|
8.3%
1/12 • Number of events 1
|
Additional Information
Dr. Mark Zalupski, M.D.
University of Michigan Comprehensive Cancer Center
Phone: 734-647-8902
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place