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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01529164
• Other study ID #: CH-GI-023
• Status: Recruiting
• Phase: Phase 2
• First received: February 4, 2012
• Last updated: November 26, 2013
• Start date: October 2011
• Est. completion date: September 2014

Study information

• Verified date: November 2013
• Source: Chinese Academy of Medical Sciences
• Contact: Wen Zhang, MD
• Phone: 86-10-87788145
• Email: wenwen0605[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 51
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Endostatins (Endostar)
7.5mg/m2 iv d1-10,repeat every 14 days,until progression or occurrence of untolerated toxicity
• Oxaliplatin
85mg/m2 iv d1 ,repeat every 14 days,until progression or occurrence of untolerated toxicity
• Leucovorin
200mg/m2 iv d1 ,repeat every 14 days
• 5-fluorouracil
400mg/m2 iv bolus,then 2400mg/m2 continuous infusion for 46 hours,repeated every 14 days,until progression or occurrence of untolerated toxicity

Locations

Country	Name	City	State
China	Cancer hospital & Institute,Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences	Simcere Pharmaceutical Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response rate	From date of treatment was administered until the date of first documented response according to RECIST criteria	3 years	No
Secondary	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	No
Secondary	overall survival	From date of treatment was administered until the date of death from any cause, assessed every 3 months.	3 years	No
Secondary	Number of participants with adverse events	assessed from the date of treatment to 1 month after stop treatment	3 years	Yes