Trial Outcomes & Findings for A Japanese Trial of TH-302 in Subjects With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma (NCT NCT02255110)

Last Updated: 2018-12-14

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

From first dose of study drug administration until PD or death, evaluated at 6 months

Results posted on

2018-12-14

Participant Flow

First/Last subject (informed consent): 10 December 2014/02 November 2015. Study completion date: 12 January 2016. Clinical data cut-off: 31 March 2016.

The study was planned to include a combination therapy period (including an initial Safety Run-In Phase followed by Phase II treatment period) and a TH-302 monotherapy period. However, due to early termination, only Safety Run-In Phase was conducted; thus, all the analyses are limited to Safety Run-In Phase.

Participant milestones

Participant milestones
Measure	TH-302 and Doxorubicin Subjects received TH-302 at a dose of 300 milligram per square meter (mg/m\^2) by intravenous infusion over 30 minutes on Day 1 and 8 of every 21-day cycle and Doxorubicin 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.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Japanese Trial of TH-302 in Subjects With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TH-302 and Doxorubicin n=6 Participants Subjects received TH-302 at a dose of 300 milligram per square meter (mg/m\^2) by intravenous infusion over 30 minutes on Day 1 and 8 of every 21-day cycle and Doxorubicin 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.
Age, Continuous	52.7 years STANDARD_DEVIATION 10.46 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose of study drug administration until PD or death, evaluated at 6 months

Population: As the study was terminated early following the discontinuation of the TH-302 clinical development program, it was decided as per Statistical Analysis Plan not to collect and evaluate the efficacy data for this study

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug administration until PD or death, evaluated at 6 months

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug administration until PD or death, evaluated at 3 months and 9 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug administration until PD or death, assessed up to 12 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug administration until PD or death, assessed up to 12 months

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug administration until PD or death, assessed up to 12 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug administration until PD or death, assessed up to 12 months

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug administration until the last subject completes the survival follow-up, assessed up to 12 months

OS is defined as the time from first dose to death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline until end of trial, assessed up to Day 210

Population: The SAF Analysis Set included all subjects who received at least 1 dose of either TH-302 or doxorubicin.

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.

Outcome measures

Outcome measures
Measure	TH-302 and Doxorubicin n=6 Participants Subjects received TH-302 at a dose of 300 milligram per square meter (mg/m\^2) by intravenous infusion over 30 minutes on Day 1 and 8 of every 21-day cycle and Doxorubicin 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.
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) (Safety Run-In Phase) TEAEs	6 Subjects
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) (Safety Run-In Phase) Serious TEAEs	4 Subjects

Adverse Events

TH-302 and Doxorubicin

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TH-302 and Doxorubicin n=6 participants at risk Subjects received TH-302 at a dose of 300 milligram per square meter (mg/m\^2) by intravenous infusion over 30 minutes on Day 1 and 8 of every 21-day cycle and Doxorubicin 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.
Infections and infestations Pneumonia	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Gastrointestinal disorders Nausea	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)

Other adverse events

Other adverse events
Measure	TH-302 and Doxorubicin n=6 participants at risk Subjects received TH-302 at a dose of 300 milligram per square meter (mg/m\^2) by intravenous infusion over 30 minutes on Day 1 and 8 of every 21-day cycle and Doxorubicin 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.
Infections and infestations Infection	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Infections and infestations Lymph gland infection	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Blood and lymphatic system disorders Anaemia	50.0% 3/6 • Baseline up to Day 210 (Safety Run-In Phase)
Blood and lymphatic system disorders Febrile neutropenia	33.3% 2/6 • Baseline up to Day 210 (Safety Run-In Phase)
Metabolism and nutrition disorders Decreased appetite	83.3% 5/6 • Baseline up to Day 210 (Safety Run-In Phase)
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 2/6 • Baseline up to Day 210 (Safety Run-In Phase)
Metabolism and nutrition disorders Hyponatraemia	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Metabolism and nutrition disorders Hypophosphataemia	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Nervous system disorders Dysgeusia	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Respiratory, thoracic and mediastinal disorders Dysphonia	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Gastrointestinal disorders Constipation	50.0% 3/6 • Baseline up to Day 210 (Safety Run-In Phase)
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Gastrointestinal disorders Nausea	83.3% 5/6 • Baseline up to Day 210 (Safety Run-In Phase)
Gastrointestinal disorders Stomatitis	50.0% 3/6 • Baseline up to Day 210 (Safety Run-In Phase)
Gastrointestinal disorders Vomiting	50.0% 3/6 • Baseline up to Day 210 (Safety Run-In Phase)
Skin and subcutaneous tissue disorders Alopecia	66.7% 4/6 • Baseline up to Day 210 (Safety Run-In Phase)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Skin and subcutaneous tissue disorders Pruritus	33.3% 2/6 • Baseline up to Day 210 (Safety Run-In Phase)
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Renal and urinary disorders Proteinuria	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
General disorders Fatigue	33.3% 2/6 • Baseline up to Day 210 (Safety Run-In Phase)
General disorders Infusion site reaction	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
General disorders Pyrexia	66.7% 4/6 • Baseline up to Day 210 (Safety Run-In Phase)
Investigations Blood alkaline phosphatase increased	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Investigations C-reactive protein increased	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Investigations Electrocardiogram QT prolonged	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Investigations Gamma-glutamyltransferase increased	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Investigations Lymphocyte count decreased	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Investigations Neutrophil count decreased	33.3% 2/6 • Baseline up to Day 210 (Safety Run-In Phase)
Investigations Platelet count decreased	50.0% 3/6 • Baseline up to Day 210 (Safety Run-In Phase)
Investigations White blood cell count decreased	50.0% 3/6 • Baseline up to Day 210 (Safety Run-In Phase)
Injury, poisoning and procedural complications Incorrect dosage administered	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)
Injury, poisoning and procedural complications Infusion related reaction	16.7% 1/6 • Baseline up to Day 210 (Safety Run-In Phase)

Additional Information

Merck KGaA Communication Center

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER