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

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

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Endostatins (Endostar); Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-fluorouracil

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.

• Study Type: Interventional
• Enrollment (Anticipated): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer hospital & Institute,Chinese Academy of Medical Sciences
      • Contact: Wen Zhang, MD; Phone Number: 86-10-87788145; Email: wenwen0605@163.com
      • Contact: Lin Yang, MD; Phone Number: 86-10-87788118; Email: lyang69@sina.com.cn
      • Principal Investigator: Lin Yang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: treatment

Drug: Endostatins (Endostar); 7.5mg/m2 iv d1-10,repeat every 14 days,until progression or occurrence of untolerated toxicity; Other Names: Endostar; Drug: Oxaliplatin; 85mg/m2 iv d1 ,repeat every 14 days,until progression or occurrence of untolerated toxicity; Other Names: Eloxatin; Drug: Leucovorin; 200mg/m2 iv d1 ,repeat every 14 days; Drug: 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: Simcere Pharmaceutical Co., Ltd
• Investigators: Principal Investigator: Lin Yang, MD, Cancer hospital&institute,Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: February 4, 2012
• First Submitted That Met QC Criteria: February 7, 2012
• First Posted (Estimate): February 8, 2012

Study Record Updates

• Last Update Posted (Estimate): November 27, 2013
• Last Update Submitted That Met QC Criteria: November 26, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: colorectal cancer; chemotherapy; endostatin; antiangiogenesis agent
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Endostar protein; Endostatins
• Other Study ID Numbers: CH-GI-023