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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by Shanghai Jiao Tong University School of Medicine.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier:
NCT00853684
First received: February 26, 2009
Last updated: September 17, 2009
Last verified: September 2009
  Purpose

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.


Condition Intervention Phase
Advanced Colorectal Cancer
Drug: OXCE
Drug: Endostar
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 Oxaliplatin, Capecitabine and Endostar as First Line Treatment for Patients With Advanced Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Shanghai Jiao Tong University School of Medicine:

Primary Outcome Measures:
  • Time to progression [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: February 2009
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: oxaliplatin, capecitabine plus endostar Drug: OXCE
Oxaliplatin 130 mg/m2 iv drip D1, Capecitabine 1000 mg/m2 bid d1-14. Every three weeks.
Other Name: Capecitabine(Xeloda®)
Drug: Endostar
Endostar 7.5 mg/m2 iv drip D1-14. Every 3 weeks.
Other Name: Endostar (a recombinant human endostatin)

Detailed Description:

Among the different combination regimens of new drugs in CRC treatment, the combination of capecitabine and oxaliplatin seems especially attractive. Both drugs have a different and relatively mild toxicity profile. In phase II studies that used the recommended dose of XELOX (capecitabine 1000 mg/m2 twice daily on days 1-14 with intravenous oxaliplatin 130 mg/m2 on day 1 every 3 weeks), RRs were between 42% and 55%, with PFS times of 6.0 to 7.7 months, which showed that the XELOX combination was effective in the first-line treatment of patients with metastatic CRC. (Cassidy et al, 2004; Scheithauer et al, 2003)

Colorectal carcinomas (CRC) are characterised by enhanced VEGF expression and the corresponding high microvascular densities, indicating increased angiogenic activity and leading to worse patient survival.(Zheng et al, 2003; Des Guetz et al, 2006) Recently, the final results of XELOX-1/NO16966, a study of first line therapy, confirmed that bevacizumab+chemotherapy (XELOX or FOLFOX) was superior to chemotherapy alone in terms of PFS (HR 0.83; p=0.0023) although the OS data did not reach statistical significance (HR 0.89; p=0.0769). (Saltz et al, 2008)

The bevacizumab data provide a treatment option for patients with metastatic CRC based on VEGF inhibition. 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, we 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00853684

Contacts
Contact: Weiguo Cao, MD +86 21 6415 5988 rjyyzlk@gmail.com

Locations
China, Shanghai
Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University Recruiting
Shanghai, Shanghai, China, 200035
Contact: Daoyuan Wang, MD    +86-13601628114    ghealth2008@gmail.com   
Principal Investigator: Weiguo Cao, MD         
Sponsors and Collaborators
Shanghai Jiao Tong University School of Medicine
Investigators
Study Chair: Weiguo Cao, MD Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University
  More Information

Publications:
Responsible Party: Shanghai Jiao Tong University School of Medicine, Ruijin Hospital
ClinicalTrials.gov Identifier: NCT00853684     History of Changes
Other Study ID Numbers: 200902024
Study First Received: February 26, 2009
Last Updated: September 17, 2009
Health Authority: China: Food and Drug Administration

Keywords provided by Shanghai Jiao Tong University School of Medicine:
Advanced Colorectal Cancer
Oxaliplatin
Capecitabine
Endostar
efficacy

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Capecitabine
Endostatins
Fluorouracil
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014