Endostar + GT in Pulmonary Metastases of Soft Tissue Sarcoma

An Open-label, Single-arm, Phase II Study to Assess the Efficacy and Safety of Endostar® (Recombinant Human Endostatin Injection) Plus Gemcitabine and Docetaxel in Treatment of Soft Tissue Sarcoma Patients With Pulmonary Metastases

The purpose of this exploratory phase II study is to assess the effectiveness and safety profile of Endostar®(Recombinant Human Endostatin Injection) plus Gemcitabine and Docetaxel in treatment of soft tissue sarcoma patients with pulmonary metastases.

Study Overview

• Status: Unknown
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Endostar; Drug: Gemcitabine; Drug: Docetaxel

Detailed Description

Anticipated 30 subjects will be enrolled to receive Endostar, Gemcitabine and Docetaxel. Endostar at a dosage of 7.5 mg/m2 will be administered on Day 1-14 of each cycle. Gemcitabine (1000 mg/m2) will be administered on Day 1 and Day 8 of each cycle. Docetaxel (75 mg/m2) will be administered on Day 2 of each cycle. An individual cycle of therapy will be defined as a 3-week (21-day) period. Cycles will be repeated every 3 weeks. Multiple cycles may be administered until the subject is PD or until a maximum of 6 cycles. Time-to-progression (TTP) will be assessed using the Kaplan Meier method. Overall response rate (ORR) as well as individual categories of response (CR, PR, SD, and PD) will be determined using RECIST (v1.1). Evaluation of 1- and 2-year overall survival will also be performed. Safety measures will be recorded using the NCI-CTCAE (v4.0).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Yuan, MD; Phone Number: 86-10-8778-8114; Email: yuanpeng01@hotmail.com

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • Contact: Peng Yuan, MD; Phone Number: 86-10-8778-8114; Email: yuanpeng01@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18-70 years, male or female.
• ECOG performance status <=2.
• Life expectancy >= 3 months.
• Histologically or cytologically confirmed soft tissue sarcoma (GIST excluded).
• Patients must have had a prior anthracycline and/or ifosfamide in either the adjuvant or metastatic setting but not more than one regimen.
• At least one measurable pulmonary metastasis tumor lesions according to RECIST 1.1 criteria.
• Laboratory values: Hemoglobin (Hb) >= 90 g/L and no blood transfusion within 14 days, Absolute neutrophil count (ANC) >= 1.5 x 10^9/L, Platelet (Plt)>= 80 x 10^9/L, Total Bilirubin (Tbil)=< 1.5 x upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN or =< 5 x ULN if liver metastases are present, Serum creatinine (Cr) =< 1.0 x ULN, Endogenous creatinine clearance (Ccr)> 50 mL/min (Cockcroft-Gault).
• Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days before enrollment and be willing to use effective contraception during study and for 8 weeks after last IMP administration.
• Willingness to participate in study and sign informed consent form.

Exclusion Criteria:

• Females who are pregnant or breastfeeding or have Childbearing potential unwilling to use effective contraception.
• Prior therapy with Gemcitabine, Docetaxel and Endostar.
• Subjects participating in other clinical trials within 4 weeks before enrollment.
• Accompanied by rapid progress of organ invasions, e.g.lesion areas are great than one half of liver or lung or have liver dysfunction.
• Uncontrolled central nervous system disorder or psychiatric illness.
• Current, serious, clinically significant cardiac arrhythmias, symptomatic congestive heart failure, myocardial infarction before enrollment.
• Patients with abnormal bone marrow function: ANC < 1.5 x 10^9/L, Plt < 75 x 10^9/L, Hb < 90g/L.
• Patients with renal dysfunction: Cr > 1.5 x ULN.
• Patients with liver dysfunction: Tbil > 1.5 x ULN.
• Uncontrolled brain metastases.
• Unwillingness or inability to comply with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Endostar; Endostar, Gemcitabine, Docetaxel

Drug: Endostar; Endostar administered at 7.5 mg/m2, intravenously (IV), on Day 1-14 every 21 days for up to 4-6 consecutive cycles; Other Names: Recombinant Human Endostatin Injection; Drug: Gemcitabine; Gemcitabine administered at 1000 mg/m2, intravenously (IV), on Day 1 and Day 8, every 21 days for up to 4-6 consecutive cycles; Drug: Docetaxel; Docetaxel administered at 75 mg/m2, intravenously (IV), on Day 2, every 21 days for up to 4-6 consecutive cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Progression	Time to progression is defined as time from first study treatment dose to the progression disease.	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate		Approximately 2 years
Evaluate 1-year and 2-year overall survival rates		Approximately 2 years
Safety measures	Adverse events, Clinical and laboratory data including physical examinations, vital signs, ECG results, Use of concomitant medications	Approximately 3 years

Collaborators and Investigators

• Sponsor: Peng Yuan
• Investigators: Principal Investigator: Peng Yuan, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Anticipated): April 1, 2015
• Study Completion (Anticipated): October 1, 2015

Study Registration Dates

• First Submitted: March 13, 2013
• First Submitted That Met QC Criteria: March 13, 2013
• First Posted (Estimate): March 15, 2013

Study Record Updates

• Last Update Posted (Estimate): March 15, 2013
• Last Update Submitted That Met QC Criteria: March 13, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Soft Tissue Sarcoma; Pulmonary metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Sarcoma; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gemcitabine; Docetaxel; Endostar protein; Endostatins
• Other Study ID Numbers: CH-SAR-001