- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03121833
Endostar Combined With Chemotherapy for Stage Ⅳ Soft Tissue Sarcoma
December 23, 2019 updated by: Tianjin Medical University Cancer Institute and Hospital
Randomized, Double-blind, Placebo-controlled (2: 1), Multicenter Clinical Study (IIB) for the Treatment of Stage Ⅳ Soft Tissue Sarcoma With Recombinant Human Endostatin(Endostar) Combined With Chemotherapy
This is a randomized, double-blind, placebo-controlled (2: 1), multicenter clinical phase II clinical trial evaluating the efficacy and safety of Endostar combined with chemotherapy for stage IV soft tissue sarcoma.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The prognosis of sarcoma patients in stage IV is poor.
For STS, the response rate of chemotherapy is only 20-35% and the median survival time is about 12 months.
The 5 year survival rate is lower than 10% reported in several large-scale studies.
Although chemotherapy plays a major role in the treatment of advanced STS, the classic chemotherapy agents are not curative.
Combination chemotherapy or dose-dense regimens have largely failed to improve the response rates.
Long-term using of cytotoxic drugs increased the risk of toxicity in patients.
Endostatin is the strongest endogenous angiogenesis inhibitor, which inhibits vascular endothelial growth factor (VEGF) expression and then inhibits tumor angiogenesis .
Endostar, is a novel recombinant human endostatin, with advantages of long half-life, stable and low cost.
Recently, a study of Endostar combined with chemotherapy in the treatment of advanced soft tissue sarcoma indicated resulted in a higher clinical benefit response (CBR) and longer progression-free survival (PFS), with tolerable side effects.
However this study included the patients with stage IIB-IV soft tissue sarcomas and did not include specific pathologic information.
Thus this clinical trial is designed to compare the efficacy and safety of endostar combined with chemotherapy versus chemotherapy alone in stage IV patients with soft tissue sarcomas.
Study Type
Interventional
Enrollment (Actual)
52
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Tianjin
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Tianjin, Tianjin, China, 300060
- Tianjin Medical University Cancer Hospital & Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 73 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients volunteered to participate in this study, signed informed consent;
- Pathological diagnosis of stage Ⅳ of soft tissue sarcoma patients, clinical staging using the American Cancer Research Joint Commission (AJCC) TNM staging criteria. There is at least one extracranial measurable lesion based on CT or MRI.
- 18 to 75 years old; the patient's physical condition Karnofsky score ≧ 60 points; ECG, blood, liver and kidney function were no abnormalities; expected survival ≧ 6 months.
Major organ function within 7 days prior to treatment, meeting the following criteria:
Blood routine examination criteria (14 days without blood transfusion):
- ①hemoglobin (HB) ≥ 90g / L;② neutrophil absolute value (ANC) ≥ 1.5 × 109 / L;③ platelet (PLT) ≥ 80 × 109 / L.
Biochemical tests to meet the following criteria:
- ①Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);② Alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2.5 × ULN, such as liver metastasis, the ALT and AST ≤ 5×ULN;③ Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 60ml / min;
- Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ normal low (50%).
- Women of childbearing age should agree that contraceptive measures (such as intrauterine devices, birth control pills or condoms) must be used within the study period and within 6 months after the end of the study; the serum or urine pregnancy test is negative within 7 days prior to the study For non-lactating patients; men should agree to patients who have contraindications during the study period and within 6 months after the end of the study period.
Exclusion Criteria:
- Patients who had previously used Endostar injections;
- Patients who have received antiangiogenic therapy or other targeted treatment for no more than 3 months, such as Endostar, Erlotinib, Sunitinib, Sorafenib, Avastin, Imatinib, Famitinib, Pazopanib and other drugs.
- 5 years or present at the same time suffering from other malignant tumors. Cured cervix in situ cancer, non-melanoma skin cancer and superficial bladder tumors except. [Ta (non-invasive tumor), Tis (orthotopic carcinoma) and T1 (tumor infiltrating basement membrane)];
- During the first 4 weeks of the group or during the study period, systemic anti-tumor therapy was planned, including cytotoxic therapy and immunotherapy. Intravenous radiotherapy (EF-RT) was performed 4 weeks prior to grouping or restricted radiotherapy was performed within 2 weeks prior to grouping to assess tumor lesions;
- Due to any previous treatment caused by the CTC AE (4.0) level 1 or more of the mitigated toxicity, excluding hair loss;
- Patients with symptoms or symptoms of control less than 2 months of brain metastases;
Any patient with severe and / or uncontrolled disease, including:
- Patients with poor blood pressure control. (Systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 100 mmHg);
- Myocardial ischemia or myocardial infarction, arrhythmia (including QTC ≥480 ms) and ≥ 2 levels of congestive heart failure (NYHA classification)
- Active or uncontrollable serious infections (≥CTC AE Level 2 infection);
- Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis to be treated with antiretroviral therapy;
- Renal failure requires hemodialysis or peritoneal dialysis;
- History of immunodeficiency, including HIV positive or other acquired, congenital immune deficiency disease, or a history of organ transplantation;
- Poor control of diabetes (fasting blood glucose (FBG)> 10mmol / L);
- Urine Urine Urine protein ≥ ++, and confirmed 24 hours urine protein> 1.0 g;
- Patients with a seizure and need treatment.
- Significant surgical treatment, biopsy or traumatic injury was received within 28 days prior to the grouping;
- Regardless of the severity of the presence of any signs of bleeding or medical history of patients; in the first 4 weeks before the group, any bleeding or bleeding events ≥ CTCAE3 patients, there is no healing wounds, ulcers or fractures;
- Subluxation / venous thrombosis events occurred within 6 months before the group, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism;
- Have a history of psychiatric abuse and can not quit or have mental disorders;
- Four weeks before the group participated in other clinical trials of anti-tumor drugs;
- According to the researcher's judgment, there are other comorbidities that seriously endanger the safety of the patient or affect the patient's completion of the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Endostar & AIM regimen / GT regimen
Endostar & AIM regimen / GT regimen; Endostar 15mg, into 500ml 0.9% sodium chloride intravenous infusion of 3 ~ 4h, d1 ~ d14, 21-28 days for a cycle; AIM regimen is Pirarubicin (THP) + Ifosfamide (IFO), the specific dose is IFO 8-12g / m2, given 4-5 days; THP 75mg / m2, given 1-2 days; 21-28 days for a cycle; GT regimen is Docetaxel (TXT) + Gemcitabine (GEM), specific dose of Gemcitabine 1000mg / m2 (D1, D8) and Docetaxel 75mg / m2 (D8); 21-28 days for a cycle; Preferred AIM regimen, AIM regimen chemotherapy failure or can not tolerate anthracycline chemotherapy in patients with GT regimen.
|
Recombinant Human Endostatin Injection
Other Names:
"Pirarubicin (THP) + Ifosfamide (IFO)" / "Docetaxel (TXT) + Gemcitabine (GEM)"
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Placebo Comparator: Placebo & AIM regimen / GT regimen
Placebo + AIM regimen / GT regimen; Placebo is 500ml 0.9% sodium chloride, Intravenous 3 ~ 4h, d1 ~ d14, 21-28 days for a cycle; The chemotherapy regimen is the same as the experimental group.
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"Pirarubicin (THP) + Ifosfamide (IFO)" / "Docetaxel (TXT) + Gemcitabine (GEM)"
500ml 0.9% sodium chloride
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival (PFS)
Time Frame: 2 year
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PFS is defined as the length of time from random assignment to disease progression or to death resulting from any cause other than the progress.
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2 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease control rate(DCR)
Time Frame: 2 year
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Investigators will assess treatment response according to Response Evaluation Criteria in Solid Tumors 1.1(RECIST1.1)
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2 year
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective tumor response rate(ORR)
Time Frame: 2 year
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ORR is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as best overall response according to radiological assessments.
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2 year
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Overall survival(OS)
Time Frame: 3 year
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OS is defined as the length of time from random assignment to death or to last contact.
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3 year
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Adverse Events(AEs)
Time Frame: 2 year
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AEs are evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.
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2 year
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Chair: Jilong Yang, M.D., Ph.D., Tianjin Medical University Cancer Institute and Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 1, 2017
Primary Completion (Actual)
December 20, 2019
Study Completion (Actual)
December 20, 2019
Study Registration Dates
First Submitted
April 17, 2017
First Submitted That Met QC Criteria
April 17, 2017
First Posted (Actual)
April 20, 2017
Study Record Updates
Last Update Posted (Actual)
December 26, 2019
Last Update Submitted That Met QC Criteria
December 23, 2019
Last Verified
December 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- S201601-IIB
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Soft Tissue Sarcoma, Adult, Stage IIB
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OHSU Knight Cancer InstituteNational Cancer Institute (NCI)WithdrawnStage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage II Adult Soft Tissue Sarcoma | Stage IIA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue Sarcoma
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National Institutes of Health Clinical Center (CC)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue Sarcoma | Stage IVB Adult Soft Tissue Sarcoma
-
Radiation Therapy Oncology GroupNational Cancer Institute (NCI)WithdrawnRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue SarcomaUnited States, Canada
-
OHSU Knight Cancer InstituteBayer; Oregon Health and Science UniversityCompletedPleomorphic Rhabdomyosarcoma | Stage III Adult Soft Tissue Sarcoma AJCC v7 | Stage IV Adult Soft Tissue Sarcoma AJCC v7 | Stage IIB Adult Soft Tissue Sarcoma AJCC v7United States
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma | Stage II Adult Soft Tissue SarcomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedStage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage IIA Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)Radiation Therapy Oncology GroupTerminatedRecurrent Adult Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma AJCC v7 | Stage II Adult Soft Tissue Sarcoma AJCC v7 | Stage III Adult Soft Tissue Sarcoma AJCC v7United States
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
Northwestern UniversityAVEO Pharmaceuticals, Inc.CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
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