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Phase I Vandetanib Plus Capecitabine, Oxaliplatin and Bevacizumab for Metastatic Colorectal Cancer
This study is currently recruiting participants.
Verified by Stanford University, June 2008
Sponsors and Collaborators: Stanford University
AstraZeneca
Information provided by: Stanford University
ClinicalTrials.gov Identifier: NCT00532909
  Purpose

To determine the maximum tolerated dose of Vandetanib with a current standard first-line chemotherapy regimen, capecitabine and oxaliplatin without and then with becavizumab for the first line treatment of metastatic colorectal cancer (CRC) and to define the dose limiting toxicities associated with the combination.


Condition Intervention Phase
Colorectal Neoplasms
Drug: Vandetanib
Drug: Capecitabine
Drug: Oxaliplatin
Drug: Bevacizumab
Phase I

MedlinePlus related topics: Cancer Colorectal Cancer
Drug Information available for: Capecitabine Bevacizumab Oxaliplatin Vandetanib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase I Trial of Vandetanib Combined With Capecitabine, Oxaliplatin and Bevacizumab for the First-Line Treatment of Metastatic Colorectal Cancer

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Maximum tolerated dose of vandetanib in combination with capecitabine, oxaliplatin and bevacizumab [Time Frame: Following treatment]

Secondary Outcome Measures:
  • Dose limiting toxicities associated with the combination [Time Frame: During and following treatment]
  • Effect of vandetanib on the pharmacokinetics (PK) of capecitabine and oxaliplatin [Time Frame: During and following treatment]
  • Effects of this treatment on tumor remission, progression free survival, and overall survival of patients [Time Frame: Following treatment]

Estimated Enrollment: 33
Study Start Date: July 2006
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:• Provision of signed informed consent.

  • Female and or male age 18 years and over.
  • Negative pregnancy test for women of childbearing potential.
  • Histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
  • Patients with a history of colorectal adenocarcinoma treated by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic colorectal adenocarcinoma if there is substantial clinical ambiguity regarding the nature or source of apparent metastases.
  • A primary or metastatic lesion measurable in at least one dimension by RECIST criteria within 4 weeks prior to entry of study
  • WHO performance status of 0-2
  • Laboratory values<= 2 weeks prior to randomization:

Absolute Neutrophil Count (ANC) >=1.5 x 109/L (>=1500/mm3) Platelets (PLT) >=100 x 109/L (>=100,000/mm3) Hemoglobin (Hgb) >=9 g/dL Serum creatinine <=1.5 x ULN Serum bilirubin <=1.5 x ULN Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <=2.5 x ULN (<=5 x ULN if liver metastases present). Note: ERCP or percutaneous stenting may be used to normalize the liver function tests.

Negative or trace for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein <=500 mg and measured creatinine clearance (CrCl) >=50 mL/min from a 24-hour urine collection

• Life expectancy >12 weeks Exclusion Criteria:• Laboratory results:

Serum bilirubin >1.5 x the upper limit of reference range (ULRR) Serum creatinine >1.5 x ULRR or creatinine clearance >= 50 mL/minute (calculated by Cockcroft-Gault formula.) Potassium, <4.0 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium out of normal range despite supplementation.

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x ULRR or alkaline phosphatase (ALP) >2.5 x ULRR, or >5x ULRR if judged by the investigator to be related to liver metastases

  • Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
  • Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >= 2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
  • History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication, is not excluded.
  • Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication.
  • Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age.
  • Presence of left bundle branch block (LBBB.)
  • QTc with Bazett's correction that is unmeasurable, or <480 msec on screening ECG. If a patient has QTc >= 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the patient to be eligible for the study.)
  • Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
  • Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
  • Currently active diarrhea that may affect the ability of the patient to absorb the vandetanib or tolerate diarrhea.
  • Women who are currently pregnant or breastfeeding.
  • Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
  • Receipt of any investigational agents within 30 days prior to commencing study treatment
  • Last dose of prior chemotherapy discontinued less than 4 weeks before the start of study therapy
  • Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy
  • Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy
  • Previous enrollment or randomization of treatment in the present study
  • Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00532909

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Heidi Kaiser     650-724-0079     hkaiser@stanford.edu    
Contact: Cancer Clinical Trials Office     (650) 498-7061        
Principal Investigator: Branimir I Sikic            
Sub-Investigator: George Albert Fisher M.D. Ph.D.            
Sub-Investigator: Elwyn Cabebe MD            
Sponsors and Collaborators
Stanford University
AstraZeneca
Investigators
Principal Investigator: Branimir I Sikic Stanford University
  More Information

Study ID Numbers: COR0006, 97132, COR0006, NCT00532909
Study First Received: September 20, 2007
Last Updated: June 16, 2008
ClinicalTrials.gov Identifier: NCT00532909  
Health Authority: United States: Food and Drug Administration;   USA:Institutional Review Board

Study placed in the following topic categories:
Oxaliplatin
Capecitabine
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Gastrointestinal Neoplasms
Bevacizumab
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009