Soft Tissue Sarcoma
Conditions
Brief summary
The purpose of this study is to evaluate the therapeutic activity and safety of E7389 in patients with advanced/metastatic soft tissue sarcoma who have failed standard chemotherapy.
Interventions
DRUGE7389
1.4 mg/m\^2 administered as an intravenous (I.V.) bolus infusion on Days 1 and 8 of every 21 days.
Sponsors
Eisai Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically proven advanced and/or metastatic malignant soft tissue sarcoma of high or intermediate grade, and of one of the following histologies (World Health Organization (WHO) classification 2002): * Leiomyosarcoma * Adipocytic (liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type not otherwise specified) * Synovial sarcoma * Other types of sarcoma, including: * Fibroblastic (adult fibrosarcoma, myxofibrosarcoma, sclerosing epithelioid fibrosarcoma). * So-called fibrohistiocytic (pleomorphic Malignant Fibrous Histiocytoma (MFH), giant cell MFH, inflammatory MFH) * Malignant glomus tumors. * Skeletal muscles (rhabdomyosarcoma, alveolar or pleomorphic) excluding embryonal rhabdomyosarcoma. * Vascular (epithelioid haemangioendothelioma, angiosarcoma). * Uncertain differentiation (synovial, epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, extra-renal rhabdoid, malignant mesenchymoma, perivascular epithelioid cell tumor (PEComa), intimal sarcoma) excluding chondrosarcoma, Ewing tumors / Primitive neuroectodermal tumor (PNET) * Malignant peripheral nerve sheath tumors. * Malignant solitary fibrous tumors. * Undifferentiated soft tissue sarcomas not otherwise specified. * Other types of sarcoma (not listed as not eligible), if approved by the Study Coordinator (written or e-mail approval needed prior to registration). * The following tumor types are not eligible: * Embryonal rhabdomyosarcoma * Chondrosarcoma * Osteosarcoma * Ewing tumors / PNET * Gastro-intestinal stromal tumors (GIST) * Dermatofibrosarcoma protuberans * Inflammatory myofibroblastic sarcoma * Neuroblastoma * Malignant mesothelioma * Mixed mesodermal tumors of the uterus 2. Formalin fixed paraffin embedded tumor blocks and representative H/E (hematoxylin/eosin) slides must be available for histological central review. Histological central review is not required before treatment start but is mandatory within 10 days of registration. Local histopathological diagnosis will be accepted for entry into the study. 3. Relapsed, refractory and/or metastatic disease incurable by surgery or radiotherapy. 4. Evidence of objective progression within the last 6 months (RECIST) documented by measurements of disease, i.e. appearance of new lesions, increase of 20% in the sum of the diameters of measurable lesions, or progression of non measurable lesions to be confirmed by an external review, without other specific treatment since objective documentation of progression. 5. Presence of measurable disease, as defined by RECIST. 6. Patients must have received no more than one combination or two single agent chemotherapy regimens for advanced disease; (neo)adjuvant therapy is not counted towards this requirement. 7. No major surgery, hormonal therapy (other than replacement), chemotherapy or radiotherapy, immunotherapy or other investigational agent within the last 28 days and/or not recovered from prior therapy within the last 28 days. Use of erythropoietin is considered supportive care and is permitted. 8. Absence of brain or subdural metastases, unless patient has completed local therapy and has discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment with E7389. Any signs (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks. 9. Absence of pre-existing neuropathy \> Grade 2 10. At least 18 years of age. 11. WHO performance status 0 or 1. 12. Adequate bone marrow function (absolute neutrophil count \>1.5 x 109/L, platelets \>100 x 109/L) 13. Adequate hepatic function (bilirubin \< 1.5 mg/mL or 25 µmol/L, SGOT/AST and SGPT/ALT \<= 3 x UNL or \< 5 x UNL in patients with liver metastases). 14. Adequate renal function: serum creatinine \< 2.0 mg/dl or 177 µmol/l or calculated (Cockcroft and Gault formula) creatinine clearance \> 40 ml/min. 15. Women should either not be of childbearing potential (having had a hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be post-menopausal with a total cessation of menses of \>1 year), or not be pregnant (negative serum pregnancy test at entry), should not be lactating, should agree to use contraceptive methods (with a documented failure rate \< 1%, vasectomized partner sterile prior to trial entry and sole sexual partner or double-barrier contraception) while on treatment and during a period of 3 months after the end of treatment. Sexually active male participants must use barrier methods of contraception. 16. Before patient registration/randomization, written informed consent must be given according to International Conference on Harmonization/Good Clinical Practice (ICH/GCP), and national/local regulations.
Exclusion criteria
1. Prior history of malignancies other than sarcoma (except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or the patient has been free of any other malignancies for \> 3 years). 2. Significant cardiovascular impairment (history of congestive heart failure \> New York Heart Association (NYHA) grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia). 3. Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency, and cannot be changed to heparin-based therapy, are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT) / international normalized ratio (INR) must be closely monitored. 4. Severe/uncontrolled intercurrent illness/infection. 5. Patients with a known hypersensitivity to halichondrin B and/or halichondrin B chemical derivative. 6. Patients who participated in a prior E7389 clinical trial. 7. Patients without freedom (by the law or administrative decision), hospitalized without their consent (mental disability, upon legal request), admitted in medical or social establishment for other reasons than clinical research, with any psychological, familial, sociological, geographical condition potentially hampering compliance with the study protocol and follow-up schedule ; those conditions should be assessed with the patient before registration in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) at 12 Weeks | Week 12 | PFS was determined from the Week 12 visit tumor scan and the participant's date of death. Progression was defined as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), early death from any cause, or not assessable according to Response Evaluation Criteria In Solid Tumors (RECIST). CR defined as the loss of all target lesions. PR defined as ≥ 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. PD defined as ≥ 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or the appearance of new lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since treatment started. The number and percentage of successes were summarized by stratum and overall, together with 95% 2-sided confidence intervals (CIs) for the percentage of successes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Date of first dose of study drug until documentation of CR or PR, or up to data cutoff 28 Jun 2012, up to approximately 5.5 years | ORR was defined as the percentage of participants in the analysis set who had a BOR of CR or PR based on RECIST v. 1.0 for target lesions. Tumors were assessed using x-rays, magnetic resonance imaging (MRI), or computed tomography (CT) scans, or both, as appropriate. ORR was documented and confirmed by two measurements taken at least 4 weeks apart. CR was defined as the disappearance of all target lesions. PR defined as ≥ 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Best overall response was derived using the same hierarchy as used when determining the PFS status at Week 12. No adjustments were made for participants who started further anticancer therapy prior to disease progression. 95% CIs were calculated using the exact method of binomial distribution. ORR = CR + PR |
| Clinical Response Benefit (CRB) | Date of first dose of study drug to documentation of CR, PR, or SD, or until data cutoff date 28 Jun 2012, up to approximately 5.5 years | CRB was defined as the percentage of participants with a BOR of CR or PR or SD as defined by RECIST, described previously. BOR was derived using the same hierarchy as used when determining the status at Week 12. No adjustments were made for participants who started further anticancer therapy prior to disease progression. 95% CIs were calculated using the exact method of binomial distribution. CRB = CR + PR + SD |
| Time to Onset of Response | Date of first dose of study drug to date of first documented CR or PR, or until data cutoff date 28 Jun 2012, up to approximately 5.5 years | Time to onset of response could be calculated only if a participant achieved an objective response (BOR of CR or PR as defined previously). Participants who never achieved CR or PR were not included in the Kaplan-Meier survival estimates for the time to onset of response by strata. Given the small number of participants with these responses and the large variation in time to onset of response between participants, no comparison could be made among the strata. |
| Overall Progression Free Survival | First dose of study drug to the date of disease progression or date of death, whichever occurs first, or date of study cut-off 28 Jun 2012, up to 5.5 years | Overall PFS was determined from any evidence that the participant had progressed, along with whether or not the participant was still alive at the end of the study. Tumors were evaluated every 6 weeks during treatment, and at least 4 weeks after the first observation of a complete or partial response. After discontinuation of study drug, participants without PD were re-evaluated every 12 weeks, unless a new anticancer therapy was started. Participants were considered as having progressed if they were classed as PD at Week 12, or had a best overall response (BOR) of PD, or had a date of progression, if they discontinued due to PD, died due to PD, or if the PI had recorded a date of progression. A participant was determined progression free if they were alive without PD at the time of study cut-off. The number and percentage of successes were summarized by stratum and overall, together with 95% 2-sided CIs for the percentage of successes. |
| Overall Survival (OS) | Date of first dose of study drug to date of death from any cause, or up to cut-off date of 28 Jun 2012, up to approximately 5.5 years | Participants still alive at the end of the study had their time to event censored at the day last known to be alive. Participants lost to follow-up were also censored at the date last known to be alive. 95% CIs for the percentage of participants still alive at the end of the study were presented as described for the primary endpoint, PFS at Week 12. |
| Summary of Adverse Events (AEs) | Day 1 of study treatment until progressive disease, or up to cut-off date of 28 Jun 2012, up to approximately 5.5 years | Treatment-emergent adverse events (TEAEs) and serious adverse events were reported. TEAEs are defined as an adverse event (AE) that emerged during treatment, having been absent at baseline or: reemerged during treatment, having been present at pretreatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. All AEs and SAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A participant was counted only once within a System Organ Class (SOC) and preferred term (PT), even if the participant experienced more than one TEAE with a specific SOC and PT. Participants were summarized by treatment group according to the worst CTCAE grade assigned for each PT. Treatment-related TEAEs included TEAEs that were considered by the investigator to be possibly or probably related to study drug or TEAEs with a missing relationship. |
| Duration of Response | Date of first documented CR or PR until the date of first document disease progression (or death), or up to data cutoff 28 Jun 2012, up to approximately 5.5 years | Duration of response could be calculated only if a participant achieved a BOR of CR or PR, as defined previously. For consistency with the formula used by the European Organization for Research and Treatment of Cancer (EORTC), the duration was derived as day of event minus day of first documented CR or PR (one was not added to the calculation). Participants who were alive without documented progression had their duration of response censored at the day of last follow-up for progression. Participants who never achieved CR or PR were not included in the Kaplan-Meier survival estimates for the duration of response by strata. No adjustment was made for participants who started further anticancer therapy prior to disease progression. |
Countries
Belgium, Denmark, France, Germany, Poland
Participant flow
Pre-assignment details
A total of 128 participants were enrolled. Of these 128 participants115 were eligible to continue in the study following reassessment of study eligibility in which 12 participants previously found eligible and began treatment, were then assessed as ineligible. One participant was not treated.
Participants by arm
| Arm | Count |
|---|---|
| Adipocyte Tumors (ADI) Participants were administered 1.4 mg/m\^2 eribulin mesilate by intravenous (IV) bolus infusion over 2 to 5 minutes on Days 1 and 8 every 21 days (21 Days = 1 Cycle) for as long as clinical benefit was sustained. The dose of study drug could have been reduced or discontinued during any treatment period, in accordance with toxicity modifications. Once the dose was reduced, it could not be increased at a later date. | 37 |
| Leiomyosarcoma (LMS) Participants were administered 1.4 mg/m\^2 eribulin mesilate by intravenous (IV) bolus infusion over 2 to 5 minutes on Days 1 and 8 every 21 days (21 Days = 1 Cycle) for as long as clinical benefit was sustained. The dose of study drug could have been reduced or discontinued during any treatmeDnt period, in accordance with toxicity modifications. Once the dose was reduced, it could not be increased at a later date. | 40 |
| Synovial Sarcoma (SYN) Participants were administered 1.4 mg/m\^2 eribulin mesilate by intravenous (IV) bolus infusion over 2 to 5 minutes on Days 1 and 8 every 21 days (21 Days = 1 Cycle) for as long as clinical benefit was sustained. The dose of study drug could have been reduced or discontinued during any treatmeDnt period, in accordance with toxicity modifications. Once the dose was reduced, it could not be increased at a later date. | 19 |
| Other Types of Sarcoma (OTH) Participants were administered 1.4 mg/m\^2 eribulin mesilate by intravenous (IV) bolus infusion over 2 to 5 minutes on Days 1 and 8 every 21 days (21 Days = 1 Cycle) for as long as clinical benefit was sustained. The dose of study drug could have been reduced or discontinued during any treatmeDnt period, in accordance with toxicity modifications. Once the dose was reduced, it could not be increased at a later date. | 31 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Disease progression | 26 | 31 | 16 | 25 |
| Overall Study | Intercurrent death | 0 | 1 | 0 | 0 |
| Overall Study | Intercurrent illness | 0 | 0 | 0 | 1 |
| Overall Study | Not treated | 0 | 0 | 0 | 1 |
| Overall Study | Other | 5 | 1 | 1 | 2 |
| Overall Study | Toxicity | 3 | 2 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 5 | 0 | 1 |
Baseline characteristics
| Characteristic | Adipocyte Tumors (ADI) | Leiomyosarcoma (LMS) | Synovial Sarcoma (SYN) | Other Types of Sarcoma (OTH) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.1 Years STANDARD_DEVIATION 11.35 | 59.9 Years STANDARD_DEVIATION 12.69 | 43.7 Years STANDARD_DEVIATION 17.92 | 53.1 Years STANDARD_DEVIATION 15.21 | 54.4 Years STANDARD_DEVIATION 14.66 |
| Sex: Female, Male Female | 11 Participants | 32 Participants | 5 Participants | 18 Participants | 66 Participants |
| Sex: Female, Male Male | 26 Participants | 8 Participants | 14 Participants | 13 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 37 | 38 / 40 | 19 / 19 | 31 / 31 |
| serious Total, serious adverse events | 14 / 37 | 12 / 40 | 7 / 19 | 14 / 31 |
Outcome results
Primary
Progression Free Survival (PFS) at 12 Weeks
PFS was determined from the Week 12 visit tumor scan and the participant's date of death. Progression was defined as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), early death from any cause, or not assessable according to Response Evaluation Criteria In Solid Tumors (RECIST). CR defined as the loss of all target lesions. PR defined as ≥ 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. PD defined as ≥ 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or the appearance of new lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since treatment started. The number and percentage of successes were summarized by stratum and overall, together with 95% 2-sided confidence intervals (CIs) for the percentage of successes.
Time frame: Week 12
Population: Efficacy evaluable set (EES) consisted of all registered, eligible subjects who had received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adipocyte Tumors (ADI) | Progression Free Survival (PFS) at 12 Weeks | 46.9 Percentage of participants |
| Leiomyosarcoma (LMS) | Progression Free Survival (PFS) at 12 Weeks | 31.6 Percentage of participants |
| Synovial Sarcoma (SYN) | Progression Free Survival (PFS) at 12 Weeks | 21.1 Percentage of participants |
| Other Types of Sarcoma (OTH) | Progression Free Survival (PFS) at 12 Weeks | 19.2 Percentage of participants |
Secondary
Clinical Response Benefit (CRB)
CRB was defined as the percentage of participants with a BOR of CR or PR or SD as defined by RECIST, described previously. BOR was derived using the same hierarchy as used when determining the status at Week 12. No adjustments were made for participants who started further anticancer therapy prior to disease progression. 95% CIs were calculated using the exact method of binomial distribution. CRB = CR + PR + SD
Time frame: Date of first dose of study drug to documentation of CR, PR, or SD, or until data cutoff date 28 Jun 2012, up to approximately 5.5 years
Population: EES
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adipocyte Tumors (ADI) | Clinical Response Benefit (CRB) | 59.4 Percentage of participants |
| Leiomyosarcoma (LMS) | Clinical Response Benefit (CRB) | 57.9 Percentage of participants |
| Synovial Sarcoma (SYN) | Clinical Response Benefit (CRB) | 47.4 Percentage of participants |
| Other Types of Sarcoma (OTH) | Clinical Response Benefit (CRB) | 46.2 Percentage of participants |
Secondary
Duration of Response
Duration of response could be calculated only if a participant achieved a BOR of CR or PR, as defined previously. For consistency with the formula used by the European Organization for Research and Treatment of Cancer (EORTC), the duration was derived as day of event minus day of first documented CR or PR (one was not added to the calculation). Participants who were alive without documented progression had their duration of response censored at the day of last follow-up for progression. Participants who never achieved CR or PR were not included in the Kaplan-Meier survival estimates for the duration of response by strata. No adjustment was made for participants who started further anticancer therapy prior to disease progression.
Time frame: Date of first documented CR or PR until the date of first document disease progression (or death), or up to data cutoff 28 Jun 2012, up to approximately 5.5 years
Population: EES
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adipocyte Tumors (ADI) | Duration of Response | 418 Days |
| Leiomyosarcoma (LMS) | Duration of Response | 129 Days |
| Synovial Sarcoma (SYN) | Duration of Response | 102 Days |
| Other Types of Sarcoma (OTH) | Duration of Response | 85 Days |
Secondary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants in the analysis set who had a BOR of CR or PR based on RECIST v. 1.0 for target lesions. Tumors were assessed using x-rays, magnetic resonance imaging (MRI), or computed tomography (CT) scans, or both, as appropriate. ORR was documented and confirmed by two measurements taken at least 4 weeks apart. CR was defined as the disappearance of all target lesions. PR defined as ≥ 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Best overall response was derived using the same hierarchy as used when determining the PFS status at Week 12. No adjustments were made for participants who started further anticancer therapy prior to disease progression. 95% CIs were calculated using the exact method of binomial distribution. ORR = CR + PR
Time frame: Date of first dose of study drug until documentation of CR or PR, or up to data cutoff 28 Jun 2012, up to approximately 5.5 years
Population: EES
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adipocyte Tumors (ADI) | Objective Response Rate (ORR) | 3.1 Percentage of participants |
| Leiomyosarcoma (LMS) | Objective Response Rate (ORR) | 5.3 Percentage of participants |
| Synovial Sarcoma (SYN) | Objective Response Rate (ORR) | 5.3 Percentage of participants |
| Other Types of Sarcoma (OTH) | Objective Response Rate (ORR) | 3.8 Percentage of participants |
Secondary
Overall Progression Free Survival
Overall PFS was determined from any evidence that the participant had progressed, along with whether or not the participant was still alive at the end of the study. Tumors were evaluated every 6 weeks during treatment, and at least 4 weeks after the first observation of a complete or partial response. After discontinuation of study drug, participants without PD were re-evaluated every 12 weeks, unless a new anticancer therapy was started. Participants were considered as having progressed if they were classed as PD at Week 12, or had a best overall response (BOR) of PD, or had a date of progression, if they discontinued due to PD, died due to PD, or if the PI had recorded a date of progression. A participant was determined progression free if they were alive without PD at the time of study cut-off. The number and percentage of successes were summarized by stratum and overall, together with 95% 2-sided CIs for the percentage of successes.
Time frame: First dose of study drug to the date of disease progression or date of death, whichever occurs first, or date of study cut-off 28 Jun 2012, up to 5.5 years
Population: EES
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adipocyte Tumors (ADI) | Overall Progression Free Survival | 82 Days |
| Leiomyosarcoma (LMS) | Overall Progression Free Survival | 88 Days |
| Synovial Sarcoma (SYN) | Overall Progression Free Survival | 81 Days |
| Other Types of Sarcoma (OTH) | Overall Progression Free Survival | 72 Days |
Secondary
Overall Survival (OS)
Participants still alive at the end of the study had their time to event censored at the day last known to be alive. Participants lost to follow-up were also censored at the date last known to be alive. 95% CIs for the percentage of participants still alive at the end of the study were presented as described for the primary endpoint, PFS at Week 12.
Time frame: Date of first dose of study drug to date of death from any cause, or up to cut-off date of 28 Jun 2012, up to approximately 5.5 years
Population: EES
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adipocyte Tumors (ADI) | Overall Survival (OS) | 363 Days |
| Leiomyosarcoma (LMS) | Overall Survival (OS) | 466 Days |
| Synovial Sarcoma (SYN) | Overall Survival (OS) | 293 Days |
| Other Types of Sarcoma (OTH) | Overall Survival (OS) | 204 Days |
Secondary
Summary of Adverse Events (AEs)
Treatment-emergent adverse events (TEAEs) and serious adverse events were reported. TEAEs are defined as an adverse event (AE) that emerged during treatment, having been absent at baseline or: reemerged during treatment, having been present at pretreatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. All AEs and SAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A participant was counted only once within a System Organ Class (SOC) and preferred term (PT), even if the participant experienced more than one TEAE with a specific SOC and PT. Participants were summarized by treatment group according to the worst CTCAE grade assigned for each PT. Treatment-related TEAEs included TEAEs that were considered by the investigator to be possibly or probably related to study drug or TEAEs with a missing relationship.
Time frame: Day 1 of study treatment until progressive disease, or up to cut-off date of 28 Jun 2012, up to approximately 5.5 years
Population: Safety analysis set included all participants who received at least one dose of study drug, regardless of their eligibility to enter the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adipocyte Tumors (ADI) | Summary of Adverse Events (AEs) | Serious TEAEs | 37.8 Percentage of participants |
| Adipocyte Tumors (ADI) | Summary of Adverse Events (AEs) | Treatment-related TEAEs | 94.6 Percentage of participants |
| Adipocyte Tumors (ADI) | Summary of Adverse Events (AEs) | TEAEs leading to death | 2.7 Percentage of participants |
| Adipocyte Tumors (ADI) | Summary of Adverse Events (AEs) | TEAEs with CTCAE Grade 3 or 4 | 54.1 Percentage of participants |
| Adipocyte Tumors (ADI) | Summary of Adverse Events (AEs) | TEAEs | 97.3 Percentage of participants |
| Leiomyosarcoma (LMS) | Summary of Adverse Events (AEs) | Serious TEAEs | 30.0 Percentage of participants |
| Leiomyosarcoma (LMS) | Summary of Adverse Events (AEs) | TEAEs with CTCAE Grade 3 or 4 | 45.0 Percentage of participants |
| Leiomyosarcoma (LMS) | Summary of Adverse Events (AEs) | TEAEs leading to death | 5.0 Percentage of participants |
| Leiomyosarcoma (LMS) | Summary of Adverse Events (AEs) | Treatment-related TEAEs | 87.5 Percentage of participants |
| Leiomyosarcoma (LMS) | Summary of Adverse Events (AEs) | TEAEs | 95.0 Percentage of participants |
| Synovial Sarcoma (SYN) | Summary of Adverse Events (AEs) | TEAEs | 100.0 Percentage of participants |
| Synovial Sarcoma (SYN) | Summary of Adverse Events (AEs) | Treatment-related TEAEs | 94.7 Percentage of participants |
| Synovial Sarcoma (SYN) | Summary of Adverse Events (AEs) | TEAEs with CTCAE Grade 3 or 4 | 47.4 Percentage of participants |
| Synovial Sarcoma (SYN) | Summary of Adverse Events (AEs) | Serious TEAEs | 36.8 Percentage of participants |
| Synovial Sarcoma (SYN) | Summary of Adverse Events (AEs) | TEAEs leading to death | 0 Percentage of participants |
| Other Types of Sarcoma (OTH) | Summary of Adverse Events (AEs) | TEAEs | 100.0 Percentage of participants |
| Other Types of Sarcoma (OTH) | Summary of Adverse Events (AEs) | TEAEs leading to death | 0 Percentage of participants |
| Other Types of Sarcoma (OTH) | Summary of Adverse Events (AEs) | TEAEs with CTCAE Grade 3 or 4 | 58.1 Percentage of participants |
| Other Types of Sarcoma (OTH) | Summary of Adverse Events (AEs) | Treatment-related TEAEs | 83.9 Percentage of participants |
| Other Types of Sarcoma (OTH) | Summary of Adverse Events (AEs) | Serious TEAEs | 45.2 Percentage of participants |
Secondary
Time to Onset of Response
Time to onset of response could be calculated only if a participant achieved an objective response (BOR of CR or PR as defined previously). Participants who never achieved CR or PR were not included in the Kaplan-Meier survival estimates for the time to onset of response by strata. Given the small number of participants with these responses and the large variation in time to onset of response between participants, no comparison could be made among the strata.
Time frame: Date of first dose of study drug to date of first documented CR or PR, or until data cutoff date 28 Jun 2012, up to approximately 5.5 years
Population: EES
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adipocyte Tumors (ADI) | Time to Onset of Response | 86 Days |
| Leiomyosarcoma (LMS) | Time to Onset of Response | 166 Days |
| Synovial Sarcoma (SYN) | Time to Onset of Response | 77 Days |
| Other Types of Sarcoma (OTH) | Time to Onset of Response | 42 Days |