Progression-free Survival, Overall Survival, Toxicity
Conditions
Keywords
soft tissue sarcoma, pegylated liposomal doxorubicin, pirarubicin, toxicity for heart, cumulative dose
Brief summary
Advanced soft tissue sarcoma patients who have previously recieved anthracyclines might still benefit from doxorubicin, ifosfamide and dacarbazine. However doxorubicin might be stopped using because of chronic cumulative heart toxicity. Several efforts have been made to improve the toxicity profile of conventional anthracyclines, including the use of liposomal encapsulation technology and the development of novel anthracycline analogs,such as pegylated liposomal doxorubicin and pirarubicin. However their actual effectiveness and toxicity have not been studied in prospective trial. The purpose of the study is to investigate whether they are available for this group of patients.
Detailed description
We design this multicentre, open-label, randomised, phase 2 trial at 5 academic hospitals in China. Eligible patients need to be aged 16 years or older with a diagnosis of an advanced unresectable or metastatic soft-tissue sarcoma, of intermediate or high grade, for which no standard curative therapy will be available, an Eastern Cooperative Oncology Group performance status of 0-1, and measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1. Participants will be randomly assigned (1:1) to receive pegylated liposomal doxorubicin (60 mg/m² via continuous intravenous infusion for 4-6 h on day 1 of every 21-day cycle for up to six cycles) or pirarubicin (30 mg/m2/d continuous intravenous infusion for 3h on day 1 and 2 of every 21-day cycle for up to six cycles) plus ifosfamide ( 2 g/m²/d intravenously for 2h on day 2,3 and 4 of every 21-day cycle for up to six cycles), dacarbazine (300 mg/m²/d intravenously for 2h on day 2,3 and 4 of every 21-day cycle for up to six cycles ).After six cycles of treatment, patients will be followed up expectantly whereas patients with stable or responsive disease are allowed to continue with ifosfamide and dacarbzine until documented disease progression. A web-based central randomisation with block sizes of two and four was stratified by extent of disease, drug administration method, and previous systemic therapy. Patients and investigators will not be masked to treatment assignment. The primary endpoint is progression survival, analysed in the intention-to-treat population. Safety analyses will be done in all patients who receive any amount of study drug.
Interventions
DRUGpegylated liposomal doxorubicin
Several efforts have been made to improve the toxicity profile of conventional anthracyclines, including the use of liposomal encapsulation technology,such as pegylated liposomal doxorubicin.
DRUGpirarubicin
Another effort has been made to improve the toxicity profile of conventional anthracyclines is the development of novel anthracycline analogs,such as pirarubicin.
Sponsors
Peking University Shougang Hospital
Chinese PLA General Hospital
Beijing Jishuitan Hospital
Xijing Hospital
Peking Union Medical College Hospital
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
A web-based central randomisation with block sizes of two and four was stratified by extent of disease,anthracycline administration method, and previous systemic therapy. Participants and investigators will not be masked to treatment assignment. The primary endpoint will be assessed in the intention-to-treat population. The outcome assessors will be masked to the two research groups.
Intervention model description
Patients will be randomly assigned (1:1) to receive pegylated liposomal doxorubicin (50 mg/m² on day 1 of every 21-day cycle for up to six cycles) or pirarubicin (60 mg/m² on day 1 of every 21-day cycle for up to six cycles) plus ifosfamide (2 g/m²/d d2-4 of every 21-day cycle for up to six cycles) and dacarbazine (300 mg/m²/d d2-4 of every 21-day cycle for up to six cycles).
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 16 years or older; * diagnosis of an advanced unresectable or metastatic soft tissue sarcoma, of intermediate or high grade, for which no standard curative therapy is available; * cumulative dose of anthracycline antibiotic ≥ 300mg/m2; * stable or responsive to doxorubicin, potential beneficiary; * an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, a life expectancy of at least 3 months; * measurable disease according to RECIST 1.1; * adequate end-organ and haemopoietic function.
Exclusion criteria
* progress over doxorubicin; * previous mediastinal or cardiac radiotherapy; * a low-grade tumour according to standard grading systems (eg, American Joint Committee on Cancer grade 1 and 2 or Fédération Nationale des Centres de Lutte Contre le Cancer grade 1); * significant cardiac dysfunction; * severe chronic obstructive pulmonary disease; * a known infection with HIV or active infection with hepatitis B or hepatitis C; * known brain metastases unless previously treated and well controlled for a period of 3 months or longer; * combination with other anti-tumor therapy; * pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| progression-free survival | 12 weeks | Progression-free survival is defined as time from randomisation to the first occurrence of progression of disease or death from any cause within 63 days of last response assessment or randomisation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate, ORR | 12 weeks | objective response rate includes complete and partial responses as defined by RECIST version 1.1. |
| left ventricular ejection fraction function | 12 months | We use ultrasound to routinely estimate the left ventricular ejection fraction function. |
| overall survival | 12 months | overall survival is defined as the duration from date of randomisation to the date of death from any cause. |
Countries
China
Outcome results
None listed