Trial Outcomes & Findings for Navitoclax and Abiraterone Acetate With or Without Hydroxychloroquine in Treating Patients With Progressive Metastatic Castrate Refractory Prostate Cancer (NCT NCT01828476)
NCT ID: NCT01828476
Last Updated: 2017-05-04
Results Overview
Characterize "biochemical response" to ABT-263 and Abiraterone and to ABT-263 in combination with hydroxychloroquine and Abiraterone by looking at PSA levels.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
13 participants
Primary outcome timeframe
5 years
Results posted on
2017-05-04
Participant Flow
Subjects were recruited through the Rutgers Cancer Institute of New Jersey. The study was open to accrual on 6/4/2013 and was closed by the Principal Investigator on 3/3/2016 due to slow accrual.
We are reporting results on 13 eligible patients. Arm A dose escalation was completed. The study was then closed to due to slow accrual and the Investigator leaving the organization.
Participant milestones
| Measure |
ARM A - Dose Escalation
Dose level 0: Abiraterone 1000 mg po daily and ABT-263 150 mg po daily Dose level 1: Abiraterone 1000 mg po daily and ABT-263 250 mg po daily\* Dose level 2 (maximum planned phase II dose): Abiraterone 1000 mg po daily and ABT-263 350 mg po daily\*
\* All patients at the 250 mg/day and 325 mg/day doses will start at 150 mg/day for the first 7 days (on Day -7) and escalated to their respective full dose on Day 1 if no DLT is observed and platelets are \>50,000/mm3.
NOTE: The dose escalation for ABT-263 combined with abiraterone was completed first prior to dose escalation with ABT-263 combined with hydroxychloroquine and abiraterone. Following both dose escalation portions of the trial, patients will then, and only then, be assigned to Arm A or Arm B of the phase II portion of the trial on a rotating basis of every other patient.
|
ARM B - Dose Escalation
Dose level 0: Abiraterone 1000 mg po daily, ABT-263 150 mg po daily, Hydroxychloroquine 200 mg po BID daily Dose level 1: Abiraterone 1000 mg po daily and ABT-263 250 mg po daily\*, Hydroxychloroquine 400 mg po BID daily Dose level 2 (maximum planned phase II dose): Abiraterone 1000 mg po daily and ABT-263 325 mg po daily\*, Hydroxychloroquine 400 mg po BID daily
\* All patients at the 250 mg/day and 325 mg/day doses will start at 150 mg/day for the first 7 days (on Day -7) and escalated to their respective full dose on Day 1 if no DLT is observed and platelets are \>50,000/mm3.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
0
|
|
Overall Study
COMPLETED
|
13
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Navitoclax and Abiraterone Acetate With or Without Hydroxychloroquine in Treating Patients With Progressive Metastatic Castrate Refractory Prostate Cancer
Baseline characteristics by cohort
| Measure |
ARM A - Dose Escalation
n=13 Participants
Dose level 0: Abiraterone 1000 mg po daily and ABT-263 150 mg po daily Dose level 1: Abiraterone 1000 mg po daily and ABT-263 250 mg po daily\* Dose level 2 (maximum planned phase II dose): Abiraterone 1000 mg po daily and ABT-263 350 mg po daily\*
\* All patients at the 250 mg/day and 325 mg/day doses will start at 150 mg/day for the first 7 days (on Day -7) and escalated to their respective full dose on Day 1 if no DLT is observed and platelets are \>50,000/mm3.
NOTE: The dose escalation for ABT-263 combined with abiraterone was completed first prior to dose escalation with ABT-263 combined with hydroxychloroquine and abiraterone. Following both dose escalation portions of the trial, patients will then, and only then, be assigned to Arm A or Arm B of the phase II portion of the trial on a rotating basis of every other patient.
|
ARM B - Dose Escalation
Dose level 0: Abiraterone 1000 mg po daily, ABT-263 150 mg po daily, Hydroxychloroquine 200 mg po BID daily Dose level 1: Abiraterone 1000 mg po daily and ABT-263 250 mg po daily\*, Hydroxychloroquine 400 mg po BID daily Dose level 2 (maximum planned phase II dose): Abiraterone 1000 mg po daily and ABT-263 325 mg po daily\*, Hydroxychloroquine 400 mg po BID daily
\* All patients at the 250 mg/day and 325 mg/day doses will start at 150 mg/day for the first 7 days (on Day -7) and escalated to their respective full dose on Day 1 if no DLT is observed and platelets are \>50,000/mm3.
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
—
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=5 Participants
|
—
|
11 Participants
n=5 Participants
|
|
Age, Continuous
|
69 years
n=5 Participants
|
—
|
69 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
—
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
—
|
13 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 5 yearsPopulation: Study was terminated early and insufficient data was collected to assess this outcome measure.
Characterize "biochemical response" to ABT-263 and Abiraterone and to ABT-263 in combination with hydroxychloroquine and Abiraterone by looking at PSA levels.
Outcome measures
| Measure |
ARM A
n=13 Participants
Abiraterone with ABT-263
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
|
ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
Hydroxychloroquine: ARM B
|
|---|---|---|
|
Biochemical Response to ABT-263 and Abiraterone and to ABT-263 in Combination With Hydroxychloroquine and Abiraterone in Patients That Are Progressing on Abiraterone
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Study was terminated early and insufficient data were collected to assess this outcome measure.
Outcome measures
| Measure |
ARM A
Abiraterone with ABT-263
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
|
ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
Hydroxychloroquine: ARM B
|
|---|---|---|
|
Time to PSA Progression
|
0
|
0
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Study was terminated early and insufficient data were collected to assess this outcome measure.
Outcome measures
| Measure |
ARM A
Abiraterone with ABT-263
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
|
ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
Hydroxychloroquine: ARM B
|
|---|---|---|
|
Progression Free Survival
|
0
|
0
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Study was terminated early and insufficent data was collected to assess this outcome measure.
Outcome measures
| Measure |
ARM A
Abiraterone with ABT-263
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
|
ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
Hydroxychloroquine: ARM B
|
|---|---|---|
|
Measurable Tumor Response in Patients With Measurable Disease
|
0
|
0
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Study was terminated early and insufficient data was collected to assess this outcome measure.
Outcome measures
| Measure |
ARM A
Abiraterone with ABT-263
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
|
ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
Hydroxychloroquine: ARM B
|
|---|---|---|
|
Circulating Tumor Cells Pre-enrollment and During Therapy
|
0
|
0
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Study was terminated warly and insufficient data was collected to assess this outcome measure.
Outcome measures
| Measure |
ARM A
Abiraterone with ABT-263
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
|
ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
Hydroxychloroquine: ARM B
|
|---|---|---|
|
Bcl-2 Family Protein Expression (Bcl-2, Bcl-XL, MCL-1) in Paraffin Blocks When Available by Immunohistochemistry
|
0
|
0
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Study was terminated early and insufficient data was collected to assess this outcome measure.
Outcome measures
| Measure |
ARM A
Abiraterone with ABT-263
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
|
ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
Hydroxychloroquine: ARM B
|
|---|---|---|
|
Biomarkers of Autophagy Modulation by EM; and LC3, and/or p62 by Immunoblotting in PBMC and Tumor Tissue When Available
|
0
|
0
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Study was terminated early and insufficient data was collected to assess this outcome measure.
Outcome measures
| Measure |
ARM A
Abiraterone with ABT-263
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
|
ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Abiraterone: ARM A and ARM B
ABT-263: ARM A and ARM B
Hydroxychloroquine: ARM B
|
|---|---|---|
|
Overall Survival
|
0
|
0
|
Adverse Events
ARM A - Dose Escalation
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
ARM B - Dose Escalation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ARM A - Dose Escalation
n=13 participants at risk
Dose level 0: Abiraterone 1000 mg po daily and ABT-263 150 mg po daily Dose level 1: Abiraterone 1000 mg po daily and ABT-263 250 mg po daily\* Dose level 2 (maximum planned phase II dose): Abiraterone 1000 mg po daily and ABT-263 350 mg po daily\*
\* All patients at the 250 mg/day and 325 mg/day doses will start at 150 mg/day for the first 7 days (on Day -7) and escalated to their respective full dose on Day 1 if no DLT is observed and platelets are \>50,000/mm3.
NOTE: The dose escalation for ABT-263 combined with abiraterone was completed first prior to dose escalation with ABT-263 combined with hydroxychloroquine and abiraterone. Following both dose escalation portions of the trial, patients will then, and only then, be assigned to Arm A or Arm B of the phase II portion of the trial on a rotating basis of every other patient.
|
ARM B - Dose Escalation
Dose level 0: Abiraterone 1000 mg po daily, ABT-263 150 mg po daily, Hydroxychloroquine 200 mg po BID daily Dose level 1: Abiraterone 1000 mg po daily and ABT-263 250 mg po daily\*, Hydroxychloroquine 400 mg po BID daily Dose level 2 (maximum planned phase II dose): Abiraterone 1000 mg po daily and ABT-263 325 mg po daily\*, Hydroxychloroquine 400 mg po BID daily
\* All patients at the 250 mg/day and 325 mg/day doses will start at 150 mg/day for the first 7 days (on Day -7) and escalated to their respective full dose on Day 1 if no DLT is observed and platelets are \>50,000/mm3.
|
|---|---|---|
|
Metabolism and nutrition disorders
Hypokalemia
|
7.7%
1/13 • Number of events 1
|
—
0/0
|
Other adverse events
| Measure |
ARM A - Dose Escalation
n=13 participants at risk
Dose level 0: Abiraterone 1000 mg po daily and ABT-263 150 mg po daily Dose level 1: Abiraterone 1000 mg po daily and ABT-263 250 mg po daily\* Dose level 2 (maximum planned phase II dose): Abiraterone 1000 mg po daily and ABT-263 350 mg po daily\*
\* All patients at the 250 mg/day and 325 mg/day doses will start at 150 mg/day for the first 7 days (on Day -7) and escalated to their respective full dose on Day 1 if no DLT is observed and platelets are \>50,000/mm3.
NOTE: The dose escalation for ABT-263 combined with abiraterone was completed first prior to dose escalation with ABT-263 combined with hydroxychloroquine and abiraterone. Following both dose escalation portions of the trial, patients will then, and only then, be assigned to Arm A or Arm B of the phase II portion of the trial on a rotating basis of every other patient.
|
ARM B - Dose Escalation
Dose level 0: Abiraterone 1000 mg po daily, ABT-263 150 mg po daily, Hydroxychloroquine 200 mg po BID daily Dose level 1: Abiraterone 1000 mg po daily and ABT-263 250 mg po daily\*, Hydroxychloroquine 400 mg po BID daily Dose level 2 (maximum planned phase II dose): Abiraterone 1000 mg po daily and ABT-263 325 mg po daily\*, Hydroxychloroquine 400 mg po BID daily
\* All patients at the 250 mg/day and 325 mg/day doses will start at 150 mg/day for the first 7 days (on Day -7) and escalated to their respective full dose on Day 1 if no DLT is observed and platelets are \>50,000/mm3.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
23.1%
3/13 • Number of events 4
|
—
0/0
|
|
Gastrointestinal disorders
Diarrhea
|
23.1%
3/13 • Number of events 13
|
—
0/0
|
|
Investigations
Platelet count decreased
|
84.6%
11/13 • Number of events 27
|
—
0/0
|
|
Investigations
Neutrophil count decreased
|
46.2%
6/13 • Number of events 19
|
—
0/0
|
|
Blood and lymphatic system disorders
Anemia
|
23.1%
3/13 • Number of events 5
|
—
0/0
|
|
General disorders
Fatigue
|
61.5%
8/13 • Number of events 12
|
—
0/0
|
|
Metabolism and nutrition disorders
Anorexia
|
46.2%
6/13 • Number of events 9
|
—
0/0
|
|
Gastrointestinal disorders
Constipation
|
7.7%
1/13 • Number of events 1
|
—
0/0
|
|
Infections and infestations
Rash pustular
|
15.4%
2/13 • Number of events 2
|
—
0/0
|
|
Gastrointestinal disorders
Flatulence
|
15.4%
2/13 • Number of events 2
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
7.7%
1/13 • Number of events 1
|
—
0/0
|
|
Metabolism and nutrition disorders
Hyponatremia
|
7.7%
1/13 • Number of events 1
|
—
0/0
|
|
Investigations
Aspartate aminotransferase increased
|
23.1%
3/13 • Number of events 3
|
—
0/0
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.7%
1/13 • Number of events 1
|
—
0/0
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
15.4%
2/13 • Number of events 2
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
1/13 • Number of events 1
|
—
0/0
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.7%
1/13 • Number of events 1
|
—
0/0
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place