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

Phase 2
18 Years
75 Years
Open (Enrolling)
Advanced Colorectal Cancer

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Trial Information

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

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.

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

- History of persistent neurosensory disorder including but not limited to peripheral

- 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

- Lack of physical integrity of the upper gastrointestinal tract or malabsorption

- Any of the following laboratory values:

- Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count < 100 x

- 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

- 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

- Karnofsky performance status <60.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to progression

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Weiguo Cao, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University


China: Food and Drug Administration

Study ID:




Start Date:

February 2009

Completion Date:

March 2011

Related Keywords:

  • Advanced Colorectal Cancer
  • Advanced Colorectal Cancer
  • Oxaliplatin
  • Capecitabine
  • Endostar
  • efficacy
  • Colorectal Neoplasms