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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase

Unknown

Phase 2

Conditions

Colorectal Cancer

Treatments

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Endostatins (Endostar)

Drug: 5-fluorouracil

Study type

Interventional

Funder types

Other

Identifiers

NCT01529164

CH-GI-023

Details and patient eligibility

About

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.

Full 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.

Enrollment

51 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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