Trial Outcomes & Findings for The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer (NCT NCT00459186)
NCT ID: NCT00459186
Last Updated: 2016-05-16
Results Overview
A dose limiting toxicity was defined as an adverse event or laboratory abnormality that occurs to patients on the Phase I portion of the trial, during the first 21 days following the first dose of RAD001/docetaxel during cycle 1, judged to be related to RAD001/docetaxel and meeting any of the following criteria: Hematologic Toxicity: CTCAE grade 4 neutropenia \> 7 days or any Grade 3 or 4 neutropenia with fever Or CTCAE grade 3 or 4 thrombocytopenia \> 7 days Non-hematologic toxicity: The occurrence of non-hematologic CTCAE grade 3 or 4 adverse events will be considered dose limiting, except for the following: 1. CTCAE grade 3 nausea or grade 3 or 4 vomiting CTCAE grade 3 or 4 vomiting will only be considered dose limiting if it occurs despite the use of standard anti-emetics. 2. CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor) 3. CTCAE grade 3 or 4 alkaline phosphatase.
COMPLETED
PHASE1/PHASE2
19 participants
21 days
2016-05-16
Participant Flow
Patients were recruited from the Genitourinary Oncology clinics of Dana-Farber Cancer Institute and the Knight Cancer Institute at Oregon Health and Science University between November, 2005 and October, 2008
Participant milestones
| Measure |
RAD001 Followed by RAD001 + Docetaxel
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
|
|---|---|
|
Single Agent RAD001
STARTED
|
19
|
|
Single Agent RAD001
COMPLETED
|
18
|
|
Single Agent RAD001
NOT COMPLETED
|
1
|
|
PET Imaging and Assessment
STARTED
|
18
|
|
PET Imaging and Assessment
COMPLETED
|
15
|
|
PET Imaging and Assessment
NOT COMPLETED
|
3
|
|
Combination RAD001 + Docetaxel
STARTED
|
15
|
|
Combination RAD001 + Docetaxel
COMPLETED
|
15
|
|
Combination RAD001 + Docetaxel
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
RAD001 Followed by RAD001 + Docetaxel
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
|
|---|---|
|
Single Agent RAD001
Withdrawal by Subject
|
1
|
|
PET Imaging and Assessment
Adverse Event
|
3
|
Baseline Characteristics
The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer
Baseline characteristics by cohort
| Measure |
RAD001 Followed by RAD001 + Docetaxel
n=18 Participants
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
|
|---|---|
|
Age, Continuous
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 21 daysPopulation: Patients who received combination treatment with RAD001 + Docetaxel
A dose limiting toxicity was defined as an adverse event or laboratory abnormality that occurs to patients on the Phase I portion of the trial, during the first 21 days following the first dose of RAD001/docetaxel during cycle 1, judged to be related to RAD001/docetaxel and meeting any of the following criteria: Hematologic Toxicity: CTCAE grade 4 neutropenia \> 7 days or any Grade 3 or 4 neutropenia with fever Or CTCAE grade 3 or 4 thrombocytopenia \> 7 days Non-hematologic toxicity: The occurrence of non-hematologic CTCAE grade 3 or 4 adverse events will be considered dose limiting, except for the following: 1. CTCAE grade 3 nausea or grade 3 or 4 vomiting CTCAE grade 3 or 4 vomiting will only be considered dose limiting if it occurs despite the use of standard anti-emetics. 2. CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor) 3. CTCAE grade 3 or 4 alkaline phosphatase.
Outcome measures
| Measure |
RAD001 Followed by RAD001 + Docetaxel
n=15 Participants
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
|
|---|---|
|
Number of Patients Free of Dose Limiting Toxicity
|
14 participants
|
SECONDARY outcome
Timeframe: 10 to 14 days after study entryPopulation: All patients receiving at least one dose of RAD001
Patients were scanned using Positron Emission Tomography (PET) before and after receiving single agent RAD001. Patients were classified as having partial metabolic response, stable metabolic disease, or progressive metabolic disease based on changes in PET imaging from baseline to post-treatment. A positive FDG-PET for the purposes of this study consisted of a visualized area of abnormal increased FDG uptake that matched the anatomic location of an abnormality seen on bone scan or CT. Metabolic response was assessed for percent change in SUVmax according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC) : partial metabolic response (PMR) ≤ -25%; stable metabolic disease (SMD) -25% + 25%; progressive metabolic disease (PMD) \> 25%.
Outcome measures
| Measure |
RAD001 Followed by RAD001 + Docetaxel
n=18 Participants
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
|
|---|---|
|
Response Based on PET Scan
Partial Metabolic Response
|
22 percentage of participants
Interval 8.0 to 44.0
|
|
Response Based on PET Scan
Stable Metabolic Disease
|
67 percentage of participants
Interval 45.0 to 84.0
|
|
Response Based on PET Scan
Progressive Metabolic Disease
|
11 percentage of participants
Interval 2.0 to 31.0
|
Adverse Events
RAD001 Followed by RAD001 + Docetaxel
Serious adverse events
| Measure |
RAD001 Followed by RAD001 + Docetaxel
n=18 participants at risk
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
5.6%
1/18
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
16.7%
3/18
|
|
Hepatobiliary disorders
Cholecystitis
|
5.6%
1/18
|
|
Infections and infestations
Infection with Grade 3-4 neutrophils - lung
|
5.6%
1/18
|
|
Infections and infestations
Infection with Grade 0-2 neutrophils - lung
|
5.6%
1/18
|
|
Investigations
Leukopenia
|
33.3%
6/18
|
|
Investigations
Neutropenia
|
44.4%
8/18
|
|
Investigations
Thrombocytopenia
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
11.1%
2/18
|
|
Metabolism and nutrition disorders
Hypokalemia
|
5.6%
1/18
|
|
Vascular disorders
Hypertension
|
5.6%
1/18
|
Other adverse events
| Measure |
RAD001 Followed by RAD001 + Docetaxel
n=18 participants at risk
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
5.6%
1/18
|
|
Gastrointestinal disorders
Diarrhea w/o prior colostomy
|
44.4%
8/18
|
|
Gastrointestinal disorders
Hemorrhoids
|
5.6%
1/18
|
|
Gastrointestinal disorders
Muco/stomatitis by exam - oral cavity
|
22.2%
4/18
|
|
Gastrointestinal disorders
Muco/stomatitis (symptom) oral cavity
|
5.6%
1/18
|
|
Gastrointestinal disorders
Nausea
|
22.2%
4/18
|
|
Gastrointestinal disorders
GI-other
|
5.6%
1/18
|
|
Gastrointestinal disorders
Abdomen - pain
|
5.6%
1/18
|
|
General disorders
Fatigue
|
44.4%
8/18
|
|
General disorders
Fever w/o neutropenia
|
11.1%
2/18
|
|
General disorders
Rigors/chills
|
5.6%
1/18
|
|
General disorders
Edema limb
|
11.1%
2/18
|
|
Infections and infestations
Infection with Grade 0-2 neutrophils - upper airway
|
11.1%
2/18
|
|
Investigations
Weight loss
|
5.6%
1/18
|
|
Investigations
Elevated AST/SGOT
|
22.2%
4/18
|
|
Investigations
Hypercholesterolemia
|
27.8%
5/18
|
|
Metabolism and nutrition disorders
Anorexia
|
11.1%
2/18
|
|
Metabolism and nutrition disorders
Hypernatremia
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
5.6%
1/18
|
|
Musculoskeletal and connective tissue disorders
Extremity-limb - pain
|
5.6%
1/18
|
|
Musculoskeletal and connective tissue disorders
Joint - pain
|
5.6%
1/18
|
|
Musculoskeletal and connective tissue disorders
Muscle - pain
|
5.6%
1/18
|
|
Nervous system disorders
Taste disturbance
|
11.1%
2/18
|
|
Nervous system disorders
Dizziness
|
5.6%
1/18
|
|
Nervous system disorders
Neuropathy-sensory
|
16.7%
3/18
|
|
Psychiatric disorders
Depression
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Nose - hemorrhage
|
16.7%
3/18
|
|
Respiratory, thoracic and mediastinal disorders
Throat/pharynx/larynx - pain
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
3/18
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
22.2%
4/18
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
11.1%
2/18
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
3/18
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
11.1%
2/18
|
|
Skin and subcutaneous tissue disorders
Hand-foot reaction
|
5.6%
1/18
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place