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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Chinese Academy of Medical Sciences
Sponsor:
Collaborator:
Simcere Pharmaceutical Co., Ltd
Information provided by (Responsible Party):
Lin Yang, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01529164
First received: February 4, 2012
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: Endostatins (Endostar)
Drug: Oxaliplatin
Drug: Leucovorin
Drug: 5-fluorouracil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Recombinant Endostatin Combined With Modified FOLFOX6 in Advanced Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Chinese Academy of Medical Sciences:

Primary Outcome Measures:
  • response rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    From date of treatment was administered until the date of first documented response according to RECIST criteria


Secondary Outcome Measures:
  • progression free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    From date of treatment was administered until the date of death from any cause, assessed every 3 months.

  • Number of participants with adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    assessed from the date of treatment to 1 month after stop treatment


Estimated Enrollment: 51
Study Start Date: October 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: treatment Drug: Endostatins (Endostar)
7.5mg/m2 iv d1-10,repeat every 14 days,until progression or occurrence of untolerated toxicity
Other Name: Endostar
Drug: Oxaliplatin
85mg/m2 iv d1 ,repeat every 14 days,until progression or occurrence of untolerated toxicity
Other Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01529164

Contacts
Contact: Wen Zhang, MD 86-10-87788145 wenwen0605@163.com
Contact: Lin Yang, MD 86-10-87788118 lyang69@sina.com.cn

Locations
China, Beijing
Cancer hospital & Institute,Chinese Academy of Medical Sciences Recruiting
Beijing, Beijing, China, 100021
Contact: Wen Zhang, MD    86-10-87788145    wenwen0605@163.com   
Contact: Lin Yang, MD    86-10-87788118    lyang69@sina.com.cn   
Principal Investigator: Lin Yang, MD         
Sponsors and Collaborators
Chinese Academy of Medical Sciences
Simcere Pharmaceutical Co., Ltd
Investigators
Principal Investigator: Lin Yang, MD Cancer hospital&institute,Chinese Academy of Medical Sciences
  More Information

No publications provided

Responsible Party: Lin Yang, associated professor, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT01529164     History of Changes
Other Study ID Numbers: CH-GI-023
Study First Received: February 4, 2012
Last Updated: November 26, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Chinese Academy of Medical Sciences:
endostatin
chemotherapy
antiangiogenesis agent
colorectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Endostatins
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on August 26, 2014