Advanced Colorectal CancerPhase 2OXCENCT00853684
Oxaliplatin, Capecitabine and Endostar as First Line Treatment for Patients With Advanced Colorectal Cancer
A Phase 2 study testing OXCE and Endostar in people with Advanced Colorectal Cancer, run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Colorectal Cancer
- What is being tested?
- OXCE and Endostar
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteChina
- Study dates
- Feb 2009to Mar 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 31Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University
Shanghai, Shanghai Municipality, 200035
Daoyuan Wang, MD, +86-13601628114, ghealth2008@gmail.com
Weiguo Cao, MD
About this study
Official title: 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.
Read the 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.
- Conditions
- Advanced Colorectal Cancer
- Being tested
- OXCE, Endostar
- Keywords
- Advanced Colorectal Cancer, Oxaliplatin, Capecitabine, Endostar, efficacy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OXCEDrug
Also called Capecitabine(Xeloda®)
Oxaliplatin 130 mg/m2 iv drip D1, Capecitabine 1000 mg/m2 bid d1-14. Every three weeks.
EndostarDrug
Also called Endostar (a recombinant human endostatin)
Endostar 7.5 mg/m2 iv drip D1-14. Every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| oxaliplatin, capecitabine plus endostar | Experimental | Not described Receives: Drug: OXCE; Drug: Endostar |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to progression
Measured: 6 months
Secondary outcomes (1)
Overall survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2009 (estimated)
- Study startFeb 2009
- Primary completionDec 2010 (estimated)
- Study completionMar 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Investigators
- Weiguo Cao, MD, Study chair, Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00853684
- Sponsor's protocol ID
- 200902024
- Acronym
- OXCE
- Status last verified
- Sep 2009
- First submitted
- 26 Feb 2009
- Last updated
- 18 Sep 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sun L, Ye HY, Zhang YH, Guan YS, Wu H. Epidermal growth factor receptor antibody plus recombinant human endostatin in treatment of hepatic metastases after remnant gastric cancer resection. World J Gastroenterol. 2007 Dec 7;13(45):6115-8. doi: 10.3748/wjg.v13.45.6115.
PubMed 18023113Xu F, Ma Q, Sha H. Optimizing drug delivery for enhancing therapeutic efficacy of recombinant human endostatin in cancer treatment. Crit Rev Ther Drug Carrier Syst. 2007;24(5):445-92. doi: 10.1615/critrevtherdrugcarriersyst.v24.i5.20.
PubMed 18197781
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Oxaliplatin, Capecitabine and Endostar as First Line Treatment for Patients With Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00853684
- Acronym / sponsor ID
- OXCE / 200902024
- Conditions
- Advanced Colorectal Cancer
- Keywords
- Advanced Colorectal Cancer, Oxaliplatin, Capecitabine, Endostar, efficacy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Dec 2010 (estimated)
- Study completion
- Mar 2011 (estimated)
- First posted
- 2 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| oxaliplatin, capecitabine plus endostar | Experimental | Drug: OXCE, Drug: Endostar |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (31 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OXCEAlso: Capecitabine(Xeloda®)Oxaliplatin 130 mg/m2 iv drip D1, Capecitabine 1000 mg/m2 bid d1-14. Every three weeks. | Drug | oxaliplatin, capecitabine plus endostar |
| EndostarAlso: Endostar (a recombinant human endostatin)Endostar 7.5 mg/m2 iv drip D1-14. Every 3 weeks. | Drug | oxaliplatin, capecitabine plus endostar |
Primary outcome
Time to progression
Time frame: 6 months
1 secondary outcome
Overall survival
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2009.
- Background: PubMed 18023113Sun L, Ye HY, Zhang YH, Guan YS, Wu H. Epidermal growth factor receptor antibody plus recombinant human endostatin in treatment of hepatic metastases after remnant gastric cancer resection. World J Gastroenterol. 2007 Dec 7;13(45):6115-8. doi: 10.3748/wjg.v13.45.6115.
- Background: PubMed 18197781Xu F, Ma Q, Sha H. Optimizing drug delivery for enhancing therapeutic efficacy of recombinant human endostatin in cancer treatment. Crit Rev Ther Drug Carrier Syst. 2007;24(5):445-92. doi: 10.1615/critrevtherdrugcarriersyst.v24.i5.20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Weiguo Cao, MD study chair
Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OXCE and Endostar in people with Advanced Colorectal Cancer, run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Weiguo Cao, MD (+86 21 6415 5988, rjyyzlk@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to progression (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00853684, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2009.