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

September 17, 2009 updated by: Shanghai Jiao Tong University School of Medicine

Phase II Study of Oxaliplatin, Capecitabine and Endostar as First Line Treatment for Patients With Advanced Colorectal Cancer

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200035
        • Recruiting
        • Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University
        • Principal Investigator:
          • Weiguo Cao, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Capecitabine(Xeloda®)
Drug: Endostar
Endostar 7.5 mg/m2 iv drip D1-14. Every 3 weeks.
Other Names:
  • Endostar (a recombinant human endostatin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to progression
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Jiao Tong University School of Medicine

Investigators

  • Study Chair: Weiguo Cao, MD, Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Anticipated)

December 1, 2010

Study Completion (Anticipated)

March 1, 2011

Study Registration Dates

First Submitted

February 26, 2009

First Submitted That Met QC Criteria

February 27, 2009

First Posted (Estimate)

March 2, 2009

Study Record Updates

Last Update Posted (Estimate)

September 18, 2009

Last Update Submitted That Met QC Criteria

September 17, 2009

Last Verified

September 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200902024

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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