Trial Outcomes & Findings for Cabozantinib and Androgen Ablation in Patients With Androgen-Dependent Metastatic Prostate Cancer (NCT NCT01630590)
NCT ID: NCT01630590
Last Updated: 2022-03-25
Results Overview
Progression defined by any of the following: (a) radiographic progression (using RECIST 1.1 for visceral disease and PCWG2 for Bone Scans), (b) receive additional anti-cancer therapy, or (c) clinical progression resulting in stopping the treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
62 participants
Primary outcome timeframe
31.2 months
Results posted on
2022-03-25
Participant Flow
Participants were enrolled from January 2014 - January 2016 at MD Anderson Cancer Center
Participant milestones
| Measure |
Cabozantinib + Androgen Ablation Therapy
Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.
Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.
Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.
|
|---|---|
|
Overall Study
STARTED
|
62
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
57
|
Reasons for withdrawal
| Measure |
Cabozantinib + Androgen Ablation Therapy
Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.
Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.
Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.
|
|---|---|
|
Overall Study
Adverse Event
|
9
|
|
Overall Study
Lack of Efficacy
|
37
|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
2nd primary tumor
|
2
|
|
Overall Study
Automobile accident
|
1
|
|
Overall Study
Maximum benefit
|
4
|
Baseline Characteristics
Only 59 of the participants had bone specific Alkaline Phosphatase level as baseline
Baseline characteristics by cohort
| Measure |
Cabozantinib + Androgen Ablation Therapy
n=62 Participants
Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.
Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.
Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.
|
|---|---|
|
Age, Continuous
|
62 years
n=62 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=62 Participants
|
|
Sex: Female, Male
Male
|
62 Participants
n=62 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=62 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
56 Participants
n=62 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=62 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=62 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=62 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=62 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=62 Participants
|
|
Race (NIH/OMB)
White
|
57 Participants
n=62 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=62 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=62 Participants
|
|
Region of Enrollment
United States
|
62 participants
n=62 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 0
|
45 Participants
n=62 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 1
|
17 Participants
n=62 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 2
|
0 Participants
n=62 Participants
|
|
Prior Treatment of Primary Tumor
No Prior Treatment
|
46 Participants
n=62 Participants
|
|
Prior Treatment of Primary Tumor
Yes Prior Treatment
|
16 Participants
n=62 Participants
|
|
Gleason Score
Gleason 6-7
|
10 Participants
n=62 Participants
|
|
Gleason Score
Gleason 7 + 5
|
2 Participants
n=62 Participants
|
|
Gleason Score
Gleason 8-10
|
45 Participants
n=62 Participants
|
|
Gleason Score
Unknown Gleason Score
|
5 Participants
n=62 Participants
|
|
Prostate Specific Antigen (PSA) Levels
|
64.7 ng/mL
n=62 Participants
|
|
Bone Specific Alkaline Phosphatase Level
|
61 µg/L
n=59 Participants • Only 59 of the participants had bone specific Alkaline Phosphatase level as baseline
|
|
Bone Metastases
Bone Metastases
|
58 Participants
n=62 Participants
|
|
Bone Metastases
Bone Only
|
27 Participants
n=62 Participants
|
|
Visceral Metastases
|
8 Participants
n=62 Participants
|
|
Soft-Tissue Metastases
None
|
29 Participants
n=62 Participants
|
|
Soft-Tissue Metastases
Lymph Nodes
|
33 Participants
n=62 Participants
|
|
Soft-Tissue Metastases
Liver
|
2 Participants
n=62 Participants
|
|
Soft-Tissue Metastases
Lung
|
6 Participants
n=62 Participants
|
|
Volume of Metastases
Low
|
8 Participants
n=62 Participants
|
|
Volume of Metastases
High
|
54 Participants
n=62 Participants
|
PRIMARY outcome
Timeframe: 31.2 monthsProgression defined by any of the following: (a) radiographic progression (using RECIST 1.1 for visceral disease and PCWG2 for Bone Scans), (b) receive additional anti-cancer therapy, or (c) clinical progression resulting in stopping the treatment.
Outcome measures
| Measure |
Cabozantinib + Androgen Ablation Therapy
n=62 Participants
Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.
Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.
Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.
|
|---|---|
|
Progression Free Survival
|
16.1 months
Interval 14.6 to 22.7
|
PRIMARY outcome
Timeframe: Start of treatment up to 30 days after study drug, up to 80 monthsNumber of instances of Serious Adverse Events and Other (Not Including Serious) Adverse Events. Adverse events were monitored for 30 days beyond the last day of treatment. These adverse events are documented. The adverse events are reported as Serious Adverse Events and Adverse Events. Serious Adverse Events are defined as adverse events in which the participant dies, is hospitalized, is disabled, or is exposed to the medicine while pregnant resulting in and birth defect. Adverse events evaluated for all treated participants using the NCI CTCAE version 4.3.
Outcome measures
| Measure |
Cabozantinib + Androgen Ablation Therapy
n=62 Participants
Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.
Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.
Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.
|
|---|---|
|
Serious Adverse Events and Other (Not Including Serious) Adverse Events
Other (Not Including Serious) Adverse Events
|
2105 adverse events
|
|
Serious Adverse Events and Other (Not Including Serious) Adverse Events
Serious Adverse Events
|
3 adverse events
|
Adverse Events
Cabozantinib + Androgen Ablation Therapy
Serious events: 3 serious events
Other events: 62 other events
Deaths: 24 deaths
Serious adverse events
| Measure |
Cabozantinib + Androgen Ablation Therapy
n=62 participants at risk
Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.
Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.
Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
1.6%
1/62 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.6%
1/62 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Renal and urinary disorders
Proteinuria
|
1.6%
1/62 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
Other adverse events
| Measure |
Cabozantinib + Androgen Ablation Therapy
n=62 participants at risk
Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.
Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.
Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
9.7%
6/62 • Number of events 8 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Alanine Aminotransferase Increase
|
80.6%
50/62 • Number of events 116 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Alkaline Phosphatase Increase
|
27.4%
17/62 • Number of events 30 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
24.2%
15/62 • Number of events 17 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Blood and lymphatic system disorders
Anemia
|
66.1%
41/62 • Number of events 56 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Anorexia
|
29.0%
18/62 • Number of events 26 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Aspartate Aminotransferase Increase
|
83.9%
52/62 • Number of events 148 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Bloating
|
4.8%
3/62 • Number of events 4 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Bilirubin Increase
|
17.7%
11/62 • Number of events 16 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Constipation
|
35.5%
22/62 • Number of events 36 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.9%
8/62 • Number of events 8 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Dehydration
|
4.8%
3/62 • Number of events 3 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Diarrhea
|
74.2%
46/62 • Number of events 142 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Nervous system disorders
Dizziness
|
16.1%
10/62 • Number of events 11 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Dry Mouth
|
12.9%
8/62 • Number of events 8 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
32.3%
20/62 • Number of events 21 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Nervous system disorders
Dysgeusia
|
59.7%
37/62 • Number of events 49 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Dyspepsia
|
11.3%
7/62 • Number of events 9 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
30.6%
19/62 • Number of events 26 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
General disorders
Edema
|
87.1%
54/62 • Number of events 120 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
General disorders
Fatigue
|
87.1%
54/62 • Number of events 120 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Flatulence
|
8.1%
5/62 • Number of events 5 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Vascular disorders
Flushing
|
4.8%
3/62 • Number of events 3 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Gastroesophageal Reflux Disease
|
29.0%
18/62 • Number of events 25 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Nervous system disorders
Headache
|
11.3%
7/62 • Number of events 8 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Renal and urinary disorders
Hematuria
|
6.5%
4/62 • Number of events 4 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Hepatobiliary disorders
Lactate Dehydrogenase Increase
|
50.0%
31/62 • Number of events 58 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
33.9%
21/62 • Number of events 25 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
6.5%
4/62 • Number of events 4 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
12.9%
8/62 • Number of events 16 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hypernatremia
|
6.5%
4/62 • Number of events 4 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
12.9%
8/62 • Number of events 8 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Vascular disorders
Hypertension
|
40.3%
25/62 • Number of events 37 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Endocrine disorders
Hyperthyroidism
|
9.7%
6/62 • Number of events 7 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
29.0%
18/62 • Number of events 36 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
12.9%
8/62 • Number of events 12 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
4.8%
3/62 • Number of events 3 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
12.9%
8/62 • Number of events 10 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
50.0%
31/62 • Number of events 67 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
8.1%
5/62 • Number of events 8 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Endocrine disorders
Hypothyroidism
|
66.1%
41/62 • Number of events 57 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Lipase Increase
|
24.2%
15/62 • Number of events 21 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Nervous system disorders
Memory Impairment
|
4.8%
3/62 • Number of events 3 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Mucositis Oral
|
29.0%
18/62 • Number of events 37 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Musculoskeletal and connective tissue disorders
Cramping in Extremities
|
11.3%
7/62 • Number of events 13 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.8%
3/62 • Number of events 3 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Nausea
|
33.9%
21/62 • Number of events 57 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Neutrophil Count Decrease
|
33.9%
21/62 • Number of events 45 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
General disorders
Non-cardiac Chest Pain
|
6.5%
4/62 • Number of events 4 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Oral Dysesthesia
|
45.2%
28/62 • Number of events 43 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Oral Pain
|
17.7%
11/62 • Number of events 12 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
General disorders
Pain
|
51.6%
32/62 • Number of events 58 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Skin and subcutaneous tissue disorders
Palmer Plantar Erythrodysesthesia
|
53.2%
33/62 • Number of events 82 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
53.2%
33/62 • Number of events 82 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Nervous system disorders
Paresthesia
|
27.4%
17/62 • Number of events 22 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Nervous system disorders
Neuropathy
|
6.5%
4/62 • Number of events 7 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Platelet Count Decrease
|
37.1%
23/62 • Number of events 29 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Renal and urinary disorders
Proteinuria
|
62.9%
39/62 • Number of events 79 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Amylase Increase
|
4.8%
3/62 • Number of events 3 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Skin and subcutaneous tissue disorders
Skin Hypopigmentation
|
9.7%
6/62 • Number of events 7 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
17.7%
11/62 • Number of events 13 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Stomach Pain
|
4.8%
3/62 • Number of events 7 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Vascular disorders
Thromboembolic Event
|
4.8%
3/62 • Number of events 4 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
|
6.5%
4/62 • Number of events 4 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Respiratory, thoracic and mediastinal disorders
Voice Alteration
|
8.1%
5/62 • Number of events 5 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Gastrointestinal disorders
Vomiting
|
22.6%
14/62 • Number of events 21 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
Weight Loss
|
12.9%
8/62 • Number of events 12 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
|
Investigations
White Blood Cell Decrease
|
46.8%
29/62 • Number of events 61 • From the first dose through 30 days after the last day of treatment, up to 80 months
|
Additional Information
Dr. Paul Corn, Chair Ad Interim, Genitourinary Medical Oncology
UT MD Anderson Cancer Center
Phone: (713) 563-7208
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place