Trial Outcomes & Findings for Carboplatin, Everolimus, and Prednisone in Treating Patients With Metastatic Prostate Cancer That Progressed After Docetaxel (NCT NCT01051570)
NCT ID: NCT01051570
Last Updated: 2020-12-01
Results Overview
Progression defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
Up to 63 days while on treatment, then up 90 days thereafter. From date of registration to date of progressive disease.
Results posted on
2020-12-01
Participant Flow
Participant milestones
| Measure |
Carboplatin, RAD 001 & Prednisone
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Carboplatin, Everolimus, and Prednisone in Treating Patients With Metastatic Prostate Cancer That Progressed After Docetaxel
Baseline characteristics by cohort
| Measure |
Carboplatin, RAD 001 & Prednisone
n=26 Participants
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Age, Continuous
|
69 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 63 days while on treatment, then up 90 days thereafter. From date of registration to date of progressive disease.Progression defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Outcome measures
| Measure |
Carboplatin, RAD 001 & Prednisone
n=26 Participants
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Time to Progression (TTP)
|
2.5 months
Interval 1.8 to 4.3
|
SECONDARY outcome
Timeframe: Day 1 of each cycle (every 21 days), through study completion, an average of 6 monthsNumber of Participants with Grade 3/4 Toxicity as measured by NCI CTCAE v3.0 criteria
Outcome measures
| Measure |
Carboplatin, RAD 001 & Prednisone
n=26 Participants
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Anemia
|
10 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Thrombocytopenia
|
9 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Lymphopenia
|
6 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Leukopenia
|
4 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Infection without neutropenia
|
4 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Hypophosphatemia
|
4 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Neutropenia
|
3 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Dehydration
|
3 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Hyperglycemia
|
3 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Hyponatremia
|
3 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Pulmonary embolism
|
2 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Fatigue
|
2 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Hypercholesterolemia
|
1 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Rash
|
1 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
AST
|
1 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Hypomagnesemia
|
1 Participants
|
|
Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
Hypokalemia
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 of each cycle (every 21 days), through study completion, an average of 6 monthsPSA response rate with response defined as =\> a 30% reduction in PSA
Outcome measures
| Measure |
Carboplatin, RAD 001 & Prednisone
n=26 Participants
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
PSA Response Rate
|
15 percentage of participants
Interval 7.0 to 30.0
|
SECONDARY outcome
Timeframe: Archival tissue will be collected if available. Optional biopsies pre-treatment and 24 hours after first everolimus and carboplatin dosePopulation: There were only 2 responders of the 10 participants who were measured for mTOR, pAKT, and p70S6.
PSA response defined as a decrease of 30% or more will be tabled against mTOR, pAKT, and p70S6 (1+, 2+, 3+ vs ND)
Outcome measures
| Measure |
Carboplatin, RAD 001 & Prednisone
n=2 Participants
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Association of PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6)
pAKT(ND) vs Responder
|
1 participants
|
|
Association of PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6)
mTOR(ND) vs Responder
|
0 participants
|
|
Association of PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6)
p70S6(ND) vs Responder
|
1 participants
|
SECONDARY outcome
Timeframe: Samples were collected Cycle 2, Day 1Population: Limited PK sampling for carboplatin were obtained at 2.75 and 24 h after the end of infusion from 8 patients.
Using a limited sampling model (i.e., AUC = 0.52 × C2.75h + 0.92) (Sorensen et al., 1993), observed carboplatin AUC was estimated based on the concentration in the 2.75-h sample.
Outcome measures
| Measure |
Carboplatin, RAD 001 & Prednisone
n=8 Participants
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Pharmacokinetics: Observed Carboplatin AUC Was Estimated Based on the Concentration in the 2.75-h Sample.
|
5.8 mg/ml*min
Interval 4.1 to 11.0
|
SECONDARY outcome
Timeframe: After treatment, participants will be contacted every 3 months up to 4 yearsOverall Survival as measured by the Kaplan-Meier method
Outcome measures
| Measure |
Carboplatin, RAD 001 & Prednisone
n=26 Participants
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Overall Survival
|
12.5 months
Interval 7.7 to 18.7
|
Adverse Events
Carboplatin, RAD 001 & Prednisone
Serious events: 10 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Carboplatin, RAD 001 & Prednisone
n=26 participants at risk
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
15.4%
4/26 • Number of events 4
|
|
Blood and lymphatic system disorders
Neutropenia
|
11.5%
3/26 • Number of events 3
|
|
Blood and lymphatic system disorders
Anemia
|
38.5%
10/26 • Number of events 10
|
|
Gastrointestinal disorders
Dehydration
|
11.5%
3/26 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
11.5%
3/26 • Number of events 3
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
34.6%
9/26 • Number of events 9
|
|
General disorders
Fatigue
|
7.7%
2/26 • Number of events 2
|
|
Vascular disorders
Thrombosis_PE
|
7.7%
2/26 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypokalemia
|
3.8%
1/26 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatremia
|
11.5%
3/26 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
15.4%
4/26 • Number of events 4
|
|
Metabolism and nutrition disorders
hypomagnesemia
|
3.8%
1/26 • Number of events 1
|
|
Blood and lymphatic system disorders
AST
|
3.8%
1/26 • Number of events 1
|
|
Blood and lymphatic system disorders
Lymphopenia
|
23.1%
6/26 • Number of events 6
|
|
Metabolism and nutrition disorders
Hypercholesterolemia
|
3.8%
1/26 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
1/26 • Number of events 1
|
|
Blood and lymphatic system disorders
Inf_wo_neutropenia
|
15.4%
4/26 • Number of events 4
|
Other adverse events
| Measure |
Carboplatin, RAD 001 & Prednisone
n=26 participants at risk
Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle
RAD 001: 5 mg Orally daily, starting from Day 2 continuously
Prednisone 5 mg Orally twice daily, continuously
carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
RAD 001: 5 mg orally starting on Day 2 then continuous
prednisone: 5 mg orally twice a day starting on Day 1 then continuous
laboratory biomarker analysis: Samples will be collected from archival tissue.
pharmacological study: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
19.2%
5/26 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
15.4%
4/26 • Number of events 4
|
|
Gastrointestinal disorders
Diarrhea
|
11.5%
3/26 • Number of events 3
|
|
Blood and lymphatic system disorders
Leukopenia
|
61.5%
16/26 • Number of events 16
|
|
Blood and lymphatic system disorders
Neutropenia
|
42.3%
11/26 • Number of events 11
|
|
Blood and lymphatic system disorders
Anemia
|
34.6%
9/26 • Number of events 9
|
|
Blood and lymphatic system disorders
Edema
|
11.5%
3/26 • Number of events 3
|
|
Gastrointestinal disorders
Dehydration
|
11.5%
3/26 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
34.6%
9/26 • Number of events 9
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
46.2%
12/26 • Number of events 12
|
|
Metabolism and nutrition disorders
Proteinuria
|
42.3%
11/26 • Number of events 11
|
|
General disorders
Fatigue
|
46.2%
12/26 • Number of events 12
|
|
Metabolism and nutrition disorders
Hypokalemia
|
34.6%
9/26 • Number of events 9
|
|
Metabolism and nutrition disorders
Hyponatremia
|
11.5%
3/26 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
7.7%
2/26 • Number of events 2
|
|
Metabolism and nutrition disorders
hypomagnesemia
|
26.9%
7/26 • Number of events 7
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
7.7%
2/26 • Number of events 2
|
|
Blood and lymphatic system disorders
AST
|
26.9%
7/26 • Number of events 7
|
|
Metabolism and nutrition disorders
Creatinine
|
23.1%
6/26 • Number of events 6
|
|
Nervous system disorders
Sensory_Neuropathy
|
7.7%
2/26 • Number of events 2
|
|
Blood and lymphatic system disorders
Lymphopenia
|
53.8%
14/26 • Number of events 14
|
|
Metabolism and nutrition disorders
Hypercholesterolemia
|
65.4%
17/26 • Number of events 17
|
|
Gastrointestinal disorders
Dyspepsia
|
7.7%
2/26 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.7%
2/26 • Number of events 2
|
|
Gastrointestinal disorders
Anorexia
|
19.2%
5/26 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
46.2%
12/26 • Number of events 12
|
|
Blood and lymphatic system disorders
Inf_wo_neutropenia
|
7.7%
2/26 • Number of events 2
|
|
Renal and urinary disorders
Hematuria
|
15.4%
4/26 • Number of events 4
|
Additional Information
Elisabeth I. Heath M.D.
Barbara Ann Karmanos Cancer Institute
Phone: 313-576-8717
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place