Clinical trial NCT01529164: Efficacy and Safety Study of Recombinant Endostatin Combined With Chemotherapy to Treat Advanced Colorectal Cancer
Official title: Phase II Study of Recombinant Endostatin Combined With Modified FOLFOX6 in Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: endostatin
chemotherapy
antiangiogenesis agent
colorectal cancer
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
Collaborators: name: Simcere Pharmaceutical Co., Ltd
First posted: 2012-02-08
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: response rate
timeFrame: 3 years
Secondary outcomes:
measure: progression free survival
timeFrame: 3 years
measure: overall survival
timeFrame: 3 years
measure: Number of participants with adverse events
timeFrame: 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer hospital & Institute,Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Cancer hospital&institute,Chinese Academy of Medical Sciences
name: Lin Yang, MD
role: PRINCIPAL_INVESTIGATOR
References: