This is a Phase 2, single-arm, Japanese multicenter trial to evaluate the safety, tolerability, and efficacy of TH-302 in combination with doxorubicin in subjects with locally advanced unresectable or metastatic soft tissue sarcoma (STS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
TH-302 will be administered at a dose of 300 milligram per square meter (mg/m\^2) by intravenous infusion over 30 minutes on Days 1 and 8 of every 21-day cycle until the evidence of significant treatment-related toxicity or progressive disease.
Doxorubicin will be administered at a dose of 75 mg/m\^2 by intravenous injection (over at least 5 minutes) or by intravenous infusion over 6-96 hours on Day 1 of every 21-day cycle starting 2 to 4 hours after completion of TH-302 administration until the evidence of significant treatment-related toxicity or progressive disease.
Research Site
Kashiwa, Japan
Research Site
Tokyo, Japan
Progression Free Survival (PFS) by Independent Central Review (Phase II Treatment Period)
PFS was planned to assess as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive Disease is defined as at least a 20 percent (%) increase in the Sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first dose of study drug administration until PD or death, evaluated at 6 months
Progression Free Survival (PFS) by Investigator Review (Phase II Treatment Period)
PFS was planned to assess as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive Disease (PD) is defined as at least a 20 percent (%) increase in the Sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first dose of study drug administration until PD or death, evaluated at 6 months
Progression-free Survival (PFS) by Investigator and Independent Central Review (Phase II Treatment Period)
PFS was planned to assess as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive Disease (PD) is defined as at least a 20 percent (%) increase in the Sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first dose of study drug administration until PD or death, evaluated at 3 months and 9 months
Progression-free Survival (PFS) (Phase II Treatment Period)
PFS was planned to assess as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive Disease (PD) is defined as at least a 20 percent (%) increase in the Sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first dose of study drug administration until PD or death, assessed up to 12 months
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Best Overall Response (BOR) by Independent Central Review (Phase II Treatment Period)
BOR was planned to be determine according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as adjudicated by an Independent Central Review. BOR is defined as the best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression or recurrence (taking the smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 millimeter (mm). PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions.
Time frame: From first dose of study drug administration until PD or death, assessed up to 12 months
Best Overall Response (BOR) by Investigator (Phase II Treatment Period)
BOR was planned to be determine according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as adjudicated by an Independent Central Review. BOR is defined as the best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression or recurrence (taking the smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 millimeter (mm). PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions.
Time frame: From first dose of study drug administration until PD or death, assessed up to 12 months
Duration of Response (Phase II Treatment Period)
Duration of response according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) is defined as the time from the first assessment of complete response (CR) or partial response (PR) until the date of the first occurrence of progressive disease (PD), or until the date of death. CR: Disappearance of all evidence of target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to less than (\<) 10 millimeter (mm). PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first dose of study drug administration until PD or death, assessed up to 12 months
Overall Survival (OS) (Phase II Treatment Period)
OS is defined as the time from first dose to death due to any cause.
Time frame: From first dose of study drug administration until the last subject completes the survival follow-up, assessed up to 12 months
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) (Safety Run-In Phase)
An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the stud drug.
Time frame: From baseline until end of trial, assessed up to Day 210