Efficacy and Safety Study of Recombinant Endostatin Combined With Chemotherapy to Treat Advanced Colorectal Cancer

Study Overview
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Brief Summary
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Studies suggest that the addition of antiangiogenic agents to conventional therapeutic strategies, e.g., chemotherapy, radiation, or other tumor-targeting agents, will increase clinical efficacy. For advanced colorectal cancer,the antiangiogenic agent bevacizumab has become an important treatment option and its combination with chemotherapy is now being one of the standard first line therapy. This phase II study was conducted to determine the efficacy and safety of another antiangiogenesis inhibitor rh-endostatin plus mFOLFOX6 in advanced colorectal cancer.

Detailed Description
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Rh-Endostatin (Endostar; Simcere Pharmaceutical Co., Ltd, JiangSu,China) is a humanized recombinant endostatin which is a direct angiogenesis inhibitor targeting the microvascular endothelial cells (ECs). A pivotal phase III study completed in China demonstrated that the addition of rh-endostatin to navelbine plus cisplatin conferred clinically significant improvements in overall survival (OS), progression-free survival (PFS), as well as response rate (RR), in patients with previously untreated metastatic non small cell lung cancer (NSCLC). In vitro, the combination of Endostatin and fluorouracil showed synergistic activity in inhibiting colon cancer. MFolfox6 was standard first-line regimen in advanced colorectal cancer. The investigators carried out a phase II trial to investigate the activity and safety of rh-endostatin plus mFOLFOX in patients with metastatic colorectal cancer.

Official Title
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Phase II Study of Recombinant Endostatin Combined With Modified FOLFOX6 in Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Endostatins (Endostar)
* Drug: Oxaliplatin
* Drug: Leucovorin
* Drug: 5-fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent (IC) Age greater than or equal to 18 years Histologically or cytologically confirmed metastatic or recurrent colorectal tumors with no previous treatment for advanced disease. At least one measurable lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by conventional techniques ECOG performance status 0-1 Life expectancy > 3 months ECG is normal Exclusion Criteria: Pregnant or lactating woman Any prior oxaliplatin treatment, with the exception of adjuvant therapy given > 12 months prior to the beginning of study therapy,and any prior 5-fluorouracil treatment, with the exception of adjuvant therapy given > 6 months prior to the beginning of study therapy Any prior endostatin treatment known hypersensitivity to 5-fluorouracil,oxaliplatin,leucovorin History of persistent neurosensory disorder including but not limited to peripheral neuropathy known DPD deficiency Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) within the last 6 months Any of the following laboratory values: Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count < 100 x 109/L) Urine protein: creatinine ratio >/= 1.0, Impaired renal function with estimated creatinine clearance < 30 ml/min Serum bilirubin > 1.5 x upper normal limit. ALT, AST > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases) Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases or > 10 x upper normal limit in the case of bone disease) use of full-dose anticoagulants or thrombolytics known CNS metastases serious nonhealing wound, ulcer, or bone fracture clinically significant bleeding diathesis or coagulopathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br> | Drug: Endostatins (Endostar)<br>* 7.5mg/m2 iv d1-10,repeat every 14 days,until progression or occurrence of untolerated toxicity<br>* Other names: Endostar;Drug: Oxaliplatin<br>* 85mg/m2 iv d1 ,repeat every 14 days,until progression or occurrence of untolerated toxicity<br>* Other names: Eloxatin;Drug: Leucovorin<br>* 200mg/m2 iv d1 ,repeat every 14 days<br>Drug: 5-fluorouracil<br>* 400mg/m2 iv bolus,then 2400mg/m2 continuous infusion for 46 hours,repeated every 14 days,until progression or occurrence of untolerated toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate | From date of treatment was administered until the date of first documented response according to RECIST criteria | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | From date of chemotherapy was administered until the date of first documented progression or date of death from any cause, whichever came first, assessed every 8 weeks. | 3 years | 
| overall survival | From date of treatment was administered until the date of death from any cause, assessed every 3 months. | 3 years | 
| Number of participants with adverse events | assessed from the date of treatment to 1 month after stop treatment | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endostatin, chemotherapy, antiangiogenesis agent, colorectal cancer