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Trial record 26 of 2026 for:    doxil

Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma

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ClinicalTrials.gov Identifier: NCT00949325
Recruitment Status : Completed
First Posted : July 30, 2009
Results First Posted : March 11, 2019
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Sarcoma
Intervention Drug: temsirolimus plus liposomal doxorubicin
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1, Dose Level 3 Cohort 2, Dose Level 4 Cohort 3, Dose Level 5
Hide Arm/Group Description Temsirolimus 15 mg/m^2 Temsirolimus 20 mg/m^2; Temsirolimus 27mg/m^2
Period Title: Overall Study
Started 3 18 3
Completed 3 16 3
Not Completed 0 2 0
Reason Not Completed
Adverse Event             0             2             0
Arm/Group Title Temsirolimus Plus Liposomal Doxorubicin
Hide Arm/Group Description

Single arm consists of temsirolimus (Torisel) plus liposomal doxorubicin (Doxil). Temsirolimus is administered IV in sequentially escalating cohorts at doses between 15 and 50 mg/M2 (body surface area), once weekly. Liposomal doxorubicin is administered IV at 30 mg per M2 (body surface area) once every 28 days. Treatment may continue with both drugs for 2 years. Temsirolimus may continue beyond 2 years.

temsirolimus plus liposomal doxorubicin: Patients will be treated with temsirolimus (Torisel) temsirolimus weekly by iv and with liposomal doxorubicin (Doxil) (standard dose) by iv once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until maximally tolerated dose (MTD) is reached. Once MTD (standard dose) is achieved, dosing will be with standard doses for each drug, but dosing will be modified based on toxicity.

Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
<=18 years
5
  20.8%
Between 18 and 65 years
17
  70.8%
>=65 years
2
   8.3%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 24 participants
39.5
(9 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
14
  58.3%
Male
10
  41.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
1.Primary Outcome
Title Part 1: Incidence of Dose Limiting Toxicities
Hide Description Dose limiting toxicities in each dose cohort.
Time Frame End of second 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Number of Subjects Who Experienced Dose-Limiting Toxicities
Hide Arm/Group Description:

Single arm consists of temsirolimus (Torisel) plus liposomal doxorubicin (Doxil). Temsirolimus is administered IV in sequentially escalating cohorts at doses between 15 and 50 mg/M2 (body surface area), once weekly. Liposomal doxorubicin is administered IV at 30 mg per M2 (body surface area) once every 28 days. Treatment may continue with both drugs for 2 years. Temsirolimus may continue beyond 2 years.

temsirolimus plus liposomal doxorubicin: Patients will be treated with temsirolimus (Torisel) temsirolimus weekly by iv and with liposomal doxorubicin (Doxil) (standard dose) by iv once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until maximally tolerated dose (MTD) is reached. Once MTD (standard dose) is achieved, dosing will be with standard doses for each drug, but dosing will be modified based on toxicity.

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
Temsirolimus 15 mg/m^2 1
Temsirolimus 20 mg/m^2 4
Temsirolimus 27 mg/m^2 3
2.Primary Outcome
Title Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Description Number of days from day 1 of treatment until date of death from any cause.
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed participants does not include the 2 participants treated at the MTD who stopped treatment for early disease-related adverse events.
Arm/Group Title Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Arm/Group Description:
Subjects who received Temsirolimus MTD, 20 mg/m^2 in Phase I of the study and all subjects in the Phase II study were included. from both Phase I and Phase II of the study are included.
Overall Number of Participants Analyzed 16
Median (Full Range)
Unit of Measure: days
254
(50 to 1532)
3.Secondary Outcome
Title Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Description Interval from Date of start of treatment to date of disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression.
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed participants does not include the 2 participants treated at the MTD who stopped treatment for early disease-related adverse events.
Arm/Group Title Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Arm/Group Description:
Subjects who received Temsirolimus MTD, 20 mg/m^2 in Phase I of the study and all subjects in the Phase II study were included from both Phase I and Phase II of the study who were not taken off study for early toxicity were included. Two of the eighteen subjects who were treated at the MTD were excluded.
Overall Number of Participants Analyzed 16
Median (Full Range)
Unit of Measure: days
74
(7 to 797)
4.Secondary Outcome
Title Objective Response Rate
Hide Description Number of participants who completed at least 2 treatment cycles with evidence of response. Response is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants who completed at least 2 treatment cycles (14/18 participants) were included to assess this outcome measure.
Arm/Group Title Temsirolimus 20 mg/m^2 and 27 mg/m^2
Hide Arm/Group Description:
Subjects who completed at least 2 cycles of treatment with temsirolimus dose of 20 mg/m^2 or 27 mg/m^2 were assessed for radiologic response.
Overall Number of Participants Analyzed 14
Measure Type: Count of Participants
Unit of Measure: Participants
CR
0
   0.0%
PR
1
   7.1%
SD
8
  57.1%
PD
5
  35.7%
5.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS
Time Frame Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
Hide Outcome Measure Data
Hide Analysis Population Description
Seven subjects had complete series of blood samples available for evaluation for both Temsirolimus, the parent drug and Sirolimus, the active metabolite. The number (N) evaluable participants is less than the number of participants from whom samples were collected due to inadvertent processing mishaps.
Arm/Group Title Temsirolimus- Parent Drug Sirolimus- Active Metabolite
Hide Arm/Group Description:
Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS
Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. Cmax of Sirolimus was calculated using a non-compartmental model.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: mg/mL
346.2  (250) 69.6  (23.2)
6.Secondary Outcome
Title Area Under the Curve (AUC)
Hide Description AUC was calculated using a single compartment model.
Time Frame Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
Hide Outcome Measure Data
Hide Analysis Population Description
Seven subjects had complete series of blood samples available for evaluation for both Temsirolimus, the parent drug and Sirolimus, the active metabolite. The analysis was per protocol. The number (N) evaluable samples is less than the number of collected samples due to inadvertent processing mishaps.
Arm/Group Title Temsirolimus- Parent Drug Sirolimus- Active Metabolite
Hide Arm/Group Description:
Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. AUC was calculated using a single compartment model.
Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. AUC was calculated using a single non- compartment model.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
1210  (340) 7499  (4591.1)
7.Secondary Outcome
Title Drug Clearance
Hide Description Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS.
Time Frame Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Temsirolimus- Parent Drug Sirolimus- Active Metabolite
Hide Arm/Group Description:
Clearance was calculated using a single compartment model.
[Not Specified]
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: L/hr/m2
17.8  (7.1) NA [1]   (NA)
[1]
Values are not available. Drug clearance was not assessed in the Sirolimus-Active Metabolite arm.
8.Secondary Outcome
Title Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Description Interval from start of treatment to disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Subjects Who Received Temsirolimus MTD, 20 mg/m^2
Hide Arm/Group Description:
All subjects who received at least one dose of temsirolimus at the MTD, 20 mg/M^2 plus liposomal doxorubicin were included.
Overall Number of Participants Analyzed 16
Mean (Full Range)
Unit of Measure: Days
195
(7 to 797)
9.Secondary Outcome
Title Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Description [Not Specified]
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who received Temsirolimus MTD, 20 mg/m^2 in Phase I of the study and all subjects in the Phase II study were included from both Phase I and Phase II of the study are included.
Arm/Group Title Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Arm/Group Description:
All subjects who received at least one dose of temsirolimus at the MTD, 20 mg/M^2 plus liposomal doxorubicin were included.
Overall Number of Participants Analyzed 16
Mean (Full Range)
Unit of Measure: Days
632
(50 to 1532)
10.Secondary Outcome
Title Time to Response
Hide Description Number of days after 2 cycles of treatment, until maximal response is observed.
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Although the original protocol specified that “time to maximal response” would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.
Arm/Group Title Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Duration of Response
Hide Description Number of days until documentation of disease progression or date of death from other cause
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Although the original protocol specified that “duration of response” would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.
Arm/Group Title Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Clinical Benefit Rate
Hide Description Number of days from documented improvement to disease progression.
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Although the original protocol specified that “clinical benefit rate” would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.
Arm/Group Title Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Temsirolimus Plus Liposomal Doxorubicin
Hide Arm/Group Description

Single arm consists of temsirolimus (Torisel) plus liposomal doxorubicin (Doxil). Temsirolimus is administered IV in sequentially escalating cohorts at doses between 15 and 50 mg/M2 (body surface area), once weekly. Liposomal doxorubicin is administered IV at 30 mg per M2 (body surface area) once every 28 days. Treatment may continue with both drugs for 2 years. Temsirolimus may continue beyond 2 years.

temsirolimus plus liposomal doxorubicin: Patients will be treated with temsirolimus (Torisel) temsirolimus weekly by iv and with liposomal doxorubicin (Doxil) (standard dose) by iv once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until maximally tolerated dose (MTD) is reached. Once MTD (standard dose) is achieved, dosing will be with standard doses for each drug, but dosing will be modified based on toxicity.

All-Cause Mortality
Temsirolimus Plus Liposomal Doxorubicin
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Temsirolimus Plus Liposomal Doxorubicin
Affected / at Risk (%) # Events
Total   7/24 (29.17%)    
Gastrointestinal disorders   
Anorexia  [1]  1/24 (4.17%)  1
General disorders   
Respiratory failure [2]  2/24 (8.33%)  2
Infections and infestations   
Fever and chills  [3]  1/24 (4.17%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea  [4]  2/24 (8.33%)  2
pneumothorax  [4]  1/24 (4.17%)  1
Plural effusion  [4]  2/24 (8.33%)  2
Indicates events were collected by systematic assessment
[1]
Required hospitalization/feeding tube
[2]
death within 30 days of ending treatment x 2 subjects
[3]
required hospitalization less than 30 days post treatment.
[4]
Required hospitalization.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Temsirolimus Plus Liposomal Doxorubicin
Affected / at Risk (%) # Events
Total   13/24 (54.17%)    
Blood and lymphatic system disorders   
Neutropenia   5/24 (20.83%)  5
anemia   1/24 (4.17%)  1
Thrombocytopenia   2/24 (8.33%)  2
Gastrointestinal disorders   
Stomatitis   2/24 (8.33%)  2
Hepatobiliary disorders   
Elevated transaminases   2/24 (8.33%)  2
Pancreatitis   1/24 (4.17%)  1
Metabolism and nutrition disorders   
Hypokalemia   2/24 (8.33%)  2
Hypocalcemia   1/24 (4.17%)  1
Hyperlipedemia   1/24 (4.17%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David M. Loeb, M.D., Ph.D.
Organization: Johns Hopkins University
Phone: 410-502-7247
EMail: loebda@jhmi.edu
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00949325     History of Changes
Other Study ID Numbers: J0963
NA_00028490 ( Other Identifier: JHMI-IRB )
First Submitted: July 28, 2009
First Posted: July 30, 2009
Results First Submitted: May 7, 2015
Results First Posted: March 11, 2019
Last Update Posted: March 11, 2019