Phase I Vandetanib Plus Capecitabine, Oxaliplatin and Bevacizumab for Metastatic Colorectal Cancer

NCT00532909 | Completed Phase 1

• 3 other identifiers: COR000697132NCT00532909
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Anal, Colon, and Rectal Cancers; Colorectal Neoplasms; Colon/Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of vandetanib in combination with capecitabine, oxaliplatin and bevacizumab

  Following treatment

Secondary Outcomes (3)

• Effect of vandetanib on the pharmacokinetics (PK) of capecitabine and oxaliplatin

  During and following treatment

• Effects of this treatment on tumor remission, progression free survival, and overall survival of patients

  Following treatment

• Dose limiting toxicities associated with the combination

  During and following treatment

Interventions

Vandetanib DRUG

100mg or 300mg By mouth every day continuous

Capecitabine DRUG

Dosage: 1000mg/m2 By mouth twice a day for 14 days or reduced dose of 800mg/m2 PO BID days1-14.

Oxaliplatin DRUG

dosage: 130mg/m2. IV Day 1 of a 21 day cycle or reduced dose of 100mg/m2 IV Day 1.

Bevacizumab DRUG

Dosage: 7.5mg/kg or 10mg/kg. IV Day 1 (21 day cycle)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 10\^9/L (\>=1500/mm\^3) Platelets (PLT) \>=100 x 10\^9/L (\>=100,000/mm\^3) 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Branimir Sikic: lead
• AstraZeneca: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms

Interventions

vandetanib; Capecitabine; Oxaliplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Colonic Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Branimir I Sikic

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 20, 2007
• First Posted: September 21, 2007
• Study Start: July 1, 2006
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: July 16, 2012

Record last verified: 2012-07

Locations

US (1)