Oxaliplatin, Capecitabine and Endostar as First Line Treatment for Patients With Advanced Colorectal Cancer

• Status: Unknown status
• Trial end date: 2011-03-01
• Target enrollment: 0
• Participant gender: All

Summary

It is hypothesized that other anti-angiogenic agents such as endostar, may augment the effect of chemotherapy regimens in CRC. Endostar, a recombinant human endostatin which expressed and purified in E. coli, was approved by the SFDA for the treatment of non-small-cell lung cancer in 2005. Ling et al. found that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, and the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. (Ling et al, 2007) A Chinese phase III clinical trial in advanced non-small-cell lung cancer, endostar--a new angiogenesis inhibitor prolonged the overall survival, time to progression and improved response rate. (Wang et al, 2005) Based on these results, the investigators design this phase II clinical trial of oxaliplatin, capecitabine and endostar as first line treatment, to evaluate whether endostar can bring survival benefits to patients with advanced colorectal cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Jiao Tong University School of Medicine
• Treatments: Capecitabine; Endostar protein; Endostatins; Oxaliplatin

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic or recurrent colorectal tumors with no previous treatment for advanced disease.

• Age greater than or equal to 18 years.

• SWOG performance status 0-1.

• 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.

• Have a negative serum pregnancy test within 7 days prior to initiation of chemotherapy (female patients of childbearing potential).

• Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of diagnosis and/or prior to study entry is required.

• Patients must agree to have a 20 cc blood sample drawn in addition to routine labs with each cycle of chemotherapy.

Exclusion Criteria:

• Pregnant or lactating woman.

• Life expectancy < 3 months.

• Serious, uncontrolled, concurrent infection(s) or illness(es)

• Any prior oxaliplatin treatment, with the exception of adjuvant therapy given > 12 months prior to the beginning of study therapy

• Prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to 5-fluorouracil, or known DPD deficiency

• Prior unanticipated severe reaction or hypersensitivity to platinum based compounds.

• Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.

• Current, recent (within 4 weeks of first infusion on this study) or planned participation in an investigational drug study.

• 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.

• History of clinically significant interstitial lung disease and/or pulmonary fibrosis.

• History of persistent neurosensory disorder including but not limited to peripheral neuropathy.

• Presence of central nervous system or brain mets.

• Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study.

• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.

• 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 as calculated with Cockroft et Gault equation:

• 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)

• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0

• Blood pressure > 150/100 mmHg

• Unstable angina

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• History of myocardial infarction or stroke within 6 months

• Clinically significant peripheral vascular disease

• Evidence of bleeding diathesis or coagulopathy

• History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0.

• Serious, non-healing wound, ulcer or bone fracture

• Carcinoma of any histology in close proximity to a major vessel, cavitation or history of hemoptysis.

• Completion of previous adjuvant chemotherapy regimen < four weeks prior to the start of study treatment (within six weeks of study treatment for mitomycin C and nitroureas), or with related toxicities unresolved prior to the start of study treatment.

• Karnofsky performance status <60.