Colorectal Cancer
Conditions
Keywords
endostatin, chemotherapy, antiangiogenesis agent, colorectal cancer
Brief summary
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
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.
Interventions
DRUGEndostatins (Endostar)
7.5mg/m2 iv d1-10,repeat every 14 days,until progression or occurrence of untolerated toxicity
DRUGOxaliplatin
85mg/m2 iv d1 ,repeat every 14 days,until progression or occurrence of untolerated toxicity
DRUGLeucovorin
200mg/m2 iv d1 ,repeat every 14 days
DRUG5-fluorouracil
400mg/m2 iv bolus,then 2400mg/m2 continuous infusion for 46 hours,repeated every 14 days,until progression or occurrence of untolerated toxicity
Sponsors
Simcere Pharmaceutical Co., Ltd
Chinese Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| response rate | 3 years | From date of treatment was administered until the date of first documented response according to RECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| progression free survival | 3 years | 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. |
| overall survival | 3 years | From date of treatment was administered until the date of death from any cause, assessed every 3 months. |
| Number of participants with adverse events | 3 years | assessed from the date of treatment to 1 month after stop treatment |
Countries
China
Contacts
Primary ContactWen Zhang, MD
Backup ContactLin Yang, MD
Outcome results
None listed