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| ID | Type | Description | Link |
|---|---|---|---|
| NA_00028490 | Other Identifier | JHMI-IRB |
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| Name | Class |
|---|---|
| National Comprehensive Cancer Network | NETWORK |
| Wyeth is now a wholly owned subsidiary of Pfizer | INDUSTRY |
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The purpose of this study is to identify a safe dosing regimen for the combination of Torisel and liposomal doxorubicin in patients with recurrent sarcoma. A secondary purpose of the study is to determine how effective this combination is for the treatment of recurrent sarcoma.
The effectiveness of treatments for recurrent sarcomas is quite limited. One hypothesis to explain the refractory nature of recurrent sarcomas is the existence of chemotherapy-resistant sarcoma stem cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| temsirolimus plus liposomal doxorubicin | Experimental | Single arm study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| temsirolimus plus liposomal doxorubicin | Drug | Patients were treated with temsirolimus (Torisel) 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 dose limiting toxicity (DLT) occurred and the maximally tolerated dose (MTD) was identified. The MTD dose was the standard dose of temsirolimus used for the remainder of the study. Dose modifications were based on protocol parameters for toxicities. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Incidence of Dose Limiting Toxicities | Dose limiting toxicities in each dose cohort. | End of second 28-day cycle |
| Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 | Number of days from day 1 of treatment until date of death from any cause. | up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David M Loeb, MD, PhD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Baltimore | Maryland | 21231 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23382028 | Result | Thornton KA, Chen AR, Trucco MM, Shah P, Wilky BA, Gul N, Carrera-Haro MA, Ferreira MF, Shafique U, Powell JD, Meyer CF, Loeb DM. A dose-finding study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcoma. Int J Cancer. 2013 Aug 15;133(4):997-1005. doi: 10.1002/ijc.28083. Epub 2013 Mar 4. | |
| 30410720 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1, Dose Level 3 | Temsirolimus 15 mg/m^2 |
| FG001 | Cohort 2, Dose Level 4 | Temsirolimus 20 mg/m^2; |
| FG002 | Cohort 3, Dose Level 5 | Temsirolimus 27mg/m^2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Temsirolimus Plus Liposomal Doxorubicin | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part 1: Incidence of Dose Limiting Toxicities | Dose limiting toxicities in each dose cohort. | Posted | Number | participants | End of second 28-day cycle |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Temsirolimus Plus Liposomal Doxorubicin | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Required hospitalization. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David M. Loeb, M.D., Ph.D. | Johns Hopkins University | 410-502-7247 | loebda@jhmi.edu |
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| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D012516 | Osteosarcoma |
| D012208 | Rhabdomyosarcoma |
| D007890 | Leiomyosarcoma |
| D012512 | Sarcoma, Ewing |
| D002813 | Chondrosarcoma |
| D008080 | Liposarcoma |
| D051677 | Histiocytoma, Malignant Fibrous |
| D018319 | Neurofibrosarcoma |
| D013584 | Sarcoma, Synovial |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018213 | Neoplasms, Bone Tissue |
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| ID | Term |
|---|---|
| C401859 | temsirolimus |
| C506643 | liposomal doxorubicin |
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|
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| up to 3 years |
| Objective Response Rate | 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 | up to 5 years |
| Maximum Observed Plasma Concentration (Cmax) | Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS | 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. |
| Area Under the Curve (AUC) | AUC was calculated using a single compartment model. | 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. |
| Drug Clearance | Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. | 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. |
| Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 | 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 | up to 3 years |
| Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 | up to 5 years |
| Time to Response | Number of days after 2 cycles of treatment, until maximal response is observed. | up to 5 years |
| Duration of Response | Number of days until documentation of disease progression or date of death from other cause | up to 5 years |
| Clinical Benefit Rate | Number of days from documented improvement to disease progression. | up to 5 years |
| Trucco MM, Meyer CF, Thornton KA, Shah P, Chen AR, Wilky BA, Carrera-Haro MA, Boyer LC, Ferreira MF, Shafique U, Powell JD, Loeb DM. A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas. Clin Sarcoma Res. 2018 Nov 5;8:21. doi: 10.1186/s13569-018-0107-9. eCollection 2018. |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
|
|
| Primary | Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 | Number of days from day 1 of treatment until date of death from any cause. | The number of analyzed participants does not include the 2 participants treated at the MTD who stopped treatment for early disease-related adverse events. | Posted | Median | Full Range | days | up to 5 years |
|
|
|
| Secondary | Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 | 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. | The number of analyzed participants does not include the 2 participants treated at the MTD who stopped treatment for early disease-related adverse events. | Posted | Median | Full Range | days | up to 3 years |
|
|
|
| Secondary | Objective Response Rate | 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 | Only participants who completed at least 2 treatment cycles (14/18 participants) were included to assess this outcome measure. | Posted | Count of Participants | Participants | up to 5 years |
|
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) | Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS | 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. | Posted | Mean | Standard Deviation | mg/mL | 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. |
|
|
|
| Secondary | Area Under the Curve (AUC) | AUC was calculated using a single compartment model. | 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. | Posted | Mean | Standard Deviation | ng*hr/ml | 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. |
|
|
|
| Secondary | Drug Clearance | Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. | Posted | Mean | Standard Deviation | L/hr/m2 | 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. |
|
|
|
| Secondary | Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 | 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 | Posted | Mean | Full Range | Days | up to 3 years |
|
|
|
| Secondary | Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 | 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. | Posted | Mean | Full Range | Days | up to 5 years |
|
|
|
| Secondary | Time to Response | Number of days after 2 cycles of treatment, until maximal response is observed. | 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. | Posted | up to 5 years |
|
|
| Secondary | Duration of Response | Number of days until documentation of disease progression or date of death from other cause | 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. | Posted | up to 5 years |
|
|
| Secondary | Clinical Benefit Rate | Number of days from documented improvement to disease progression. | 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. | Posted | up to 5 years |
|
|
| 7 |
| 24 |
| 13 |
| 24 |
|
| pneumothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Required hospitalization. |
|
| Plural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Required hospitalization. |
|
| Respiratory failure | General disorders | death within 30 days of ending treatment x 2 subjects |
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| Anorexia | Gastrointestinal disorders | Systematic Assessment | Required hospitalization/feeding tube |
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| Fever and chills | Infections and infestations | Systematic Assessment | required hospitalization less than 30 days post treatment. |
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| anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Elevated transaminases | Hepatobiliary disorders | Systematic Assessment |
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| Hyperlipedemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | Systematic Assessment |
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| Pancreatitis | Hepatobiliary disorders | Systematic Assessment |
|
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| D009372 | Neoplasms, Connective Tissue |
| D009217 | Myosarcoma |
| D009379 | Neoplasms, Muscle Tissue |
| D018205 | Neoplasms, Adipose Tissue |
| D051642 | Histiocytoma |
| D018218 | Neoplasms, Fibrous Tissue |
| D005354 | Fibrosarcoma |
| D009455 | Neurofibroma |
| D018317 | Nerve Sheath Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D010524 | Peripheral Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009422 | Nervous System Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| Title | Measurements |
|---|
|
| PD |
|