Recombinant Human Endostatin in Combination With mFOLFOX6 in Patients With Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01310478
Recruitment Status : Unknown
Verified June 2010 by Fudan University.
Recruitment status was:  Recruiting
First Posted : March 8, 2011
Last Update Posted : March 8, 2011
Information provided by:
Fudan University

Brief Summary:
To investigate safety and tolerance of dose-escalation of infusional recombinant human endostatin in combination with mFOLFOX6 as initial therapy for patients with metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasm Drug: recombinant human endostatin (Endostat) Phase 1

Detailed Description:
Recombinant human endostatin(Endostar) is commonly used through intermittent intravenous adminstration in routine clinical practice in China. It is very difficult to maintain steady-state of plasma concentration of this agent due to this manner of application. Continous infusional Endostar was designed to alter the imblance of concentration to avoid compromising efficacy of anti-angionesis therapy.The strategy of dose-escalation was used in this study in order to obtain the optimal dosage of Endostar for the next phase Ⅱ trial.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: PhaseⅠClinical Study of Recombinant Human Endostatin in Combination With mFOLFOX6 as Initial Therapy for Patients With Metastatic Colorectal Cancer
Study Start Date : August 2010
Estimated Primary Completion Date : May 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Endostar combined with mFOLFOX6 Drug: recombinant human endostatin (Endostat)
mFOLFOX6:Oxaliplatin 85 mg/m2 d1 Leucovorin 400 mg/m2 d1+5-FU 400 mg/m2 bolus d1+5-FU 2.4 CIV 46h Endostar 7.5mg/m2/d~45mg/m2/d continous intravenous d4~d14
Other Name: Endostar

Primary Outcome Measures :
  1. Dose limiting toxicity and maximum tolerance dose of continous intravenous Endostar in combination with mFOLFOX6 [ Time Frame: 14 days ]

Secondary Outcome Measures :
  1. Parameters of human pharmacokinetics of continous intravenous Endostar in combination with mFOLFOX6 [ Time Frame: 11 days ]

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Ages Eligible for Study:   17 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Provision of written informed consent
  2. Histological or cytological confirmed adenocarcinoma of the colon or rectum
  3. Age between 18 and 70 years.
  4. Patients must have received no prior systemic therapy for metastatic disease. Anyadjuvant/neoadjuvant oxaliplatin therapy must have been received >12 months prior to study entry and adjuvant/neoadjuvant 5-FU must have been received >6 months prior to study entry. Patients who have previously been disease free following a neoadjuvant chemotherapy regimen and resection of all primary tumour and metastatic disease are eligible..
  5. ECOG Performance Status of 0 or1
  6. Life expectancy of at least 12 weeks
  7. The required evidence of measurable lesions should be at least 10 mm in the longest diameter by spiral computed tomography scan or 20 mm with conventional techniques (RECIST criteria)
  8. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

    • Hemoglobin > 9.0 g/dl
    • Absolute neutrophil count (ANC) >1,500/mm3
    • Platelet count 100,000/μl
    • Total bilirubin < 1.5 times the upper limit of normal ALT and AST < 2.5 x ULN(< 5 x ULN for patients with liver involvement of their cancer)
    • ALP< 4 x ULN
    • PT-INR/PTT < 1.5 x upper limit of normal
    • Serum creatinine < 1.5 x ULN

Exclusion Criteria:

  1. History of cardiac disease:

    • congestive heart failure >NYHA class 2
    • with a history of symptomatic coronary artery disease(including angina and myocardial infarction) or other ischemic heart disease
    • cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
  2. History of HIV infection or chronic hepatitis B or C (high copy number of HBV).
  3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
  4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
  5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
  6. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma within 5 years.
  7. Recent (<28 days) major thoracic or abdominal surgery prior to entry into the studyor a surgical incision that is not fully healed
  8. Known hypersensitivity to recombinant human endostatin, oxaliplatin, 5-FU, leucovorin, capecitabine or any of the excipients of these products
  9. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  10. Peripheral neuropathy ≥CTC grade 2
  11. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
  12. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial (and men for at least 3 months after last administration of study medication).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01310478

Contact: Zhiyu Chen, MD +862164175590

China, Shanghai
Shanghai Cancer Center Recruiting
Shanghai, Shanghai, China
Contact: Zhiyu Chen, MD         
Principal Investigator: Jin Li, MD         
Sponsors and Collaborators
Fudan University
Principal Investigator: Jin Li, MD Fudan University

Responsible Party: Base for drug clinical trials,Shanghai Cancer Center, Fudan University, Department of medical oncology, Shanghai Cancer Center,Fuandan University Identifier: NCT01310478     History of Changes
Other Study ID Numbers: SIM-85
First Posted: March 8, 2011    Key Record Dates
Last Update Posted: March 8, 2011
Last Verified: June 2010

Keywords provided by Fudan University:
Recombinant human endostatin
Metastatic colorectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors