A Phase II, Double-Blind, Placebo Controlled, Randomised Study To Assess The Efficacy And Safety Of 2 Doses Of ZACTIMA (ZD6474) In Combination With FOLFOX vs FOLFOX Alone For The Treatment Of Colorectal Cancer In Patients Who Have Failed Therapy With An Irinotecan And Fluoropyrimidine Containing Regimen.

Phase 1

• Conditions: Colorectal cancer; MedDRA version: 8.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer

• Registration Number: EUCTR2006-005022-23-FR
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-12
• Last Update Posted: 10 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

1.Have histologically confirmed colorectal cancer.
2.Have failed therapy with an irinotecan and fluoropyrimidine containing regimen defined as:
-Progression on or following treatment for metastatic colorectal cancer
-Progression within 12 months of adjuvant chemotherapy for colorectal cancer.
3.Have World Health Organisation (WHO) performance status 0-2 and life expectancy > 12 weeks.
4. Are suitable for treatment with oxaliplatin, 5-FU and leucovorin (FOLFOX) (see Appendix E of protocol).
5.Be aged at least 18 years.
6.Provide written informed consent to participate in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Previous treatment with small molecule tyrosine kinase inhibitors of VEGFR or EGFR eg, erlotinib, gefitinib. Prior monoclonal antibodies are permitted eg, cetuximab, bevacizumab.
2.Previous adjuvant therapy with oxaliplatin within 12 months of randomisation.
3.More than one prior course of chemotherapy for treatment of metastatic colorectal cancer.
4.Any recent surgery, unhealed surgical incision or severe concomitant condition which, in the Investigator’s opinion, makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the study protocol.
5.Current or prior malignancy within previous 3 years (other than colorectal cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix).
6.Brain metastases or spinal cord compression unless treated and stable off steroids for one month.
7.With the exception of alopecia, any unresolved toxicity = CTCAE grade 2 from previous anticancer therapy. (unless specified else where within these selection criteria)
8.Persistent neuropathy following prior oxaliplatin therapy.
9.At time of randomisation less than 4 weeks since completion of prior radiotherapy to the primary tumour or persistence of any acute radiotherapy toxicity.
10.Chronic inflammatory bowel disease, bowel obstruction or other current active gastrointestinal disease.
11.Significant cardiovascular event (eg, myocardial infarction, New York Heart Association classification of heart disease (NYHA) = 2) within 3 months of randomisation, or presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
12.History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, symptomatic or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication, is not excluded.
13.Left bundle branch block.
14.Hypertension not controlled by medical therapy (systolic blood pressure > 160 mmHg or diastolic blood pressure > 110 mmHg).
15.Baseline mean QTc measurement = 480ms using Bazett’s formula.
16.Patients with factors that increase risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of unexplained sudden death under 40 years of age or any concomitant medication known to prolong QTc.
17.Any of the following laboratory values:
-Potassium <4.0 mmol/l despite supplementation
-Calcium (or calcium adjusted for albumen) or magnesium out of normal range despite supplementation.
18.Any of the following laboratory values:
-Total bilirubin > 1.5 x ULN (upper limit of normal)
-Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULN if no demonstrable liver metastases or > 5 x ULN in presence of liver metastases.
19.Any of the following laboratory values:
-Platelets < 100 x10e9/l.
-Haemoglobin < 9 g/dl despite transfusion
-Absolute neutrophil count < 2.0 x10e9/l.
20.Creatinine clearance < 50 ml/min and/or an elevated serum creatinine > 1.5 ULN.
21.Presence of clinically significant blood or protein on repeat urine labstix test.
22.Concomitant use of the inducers of CYP3A4 (eg, phenytoin, rifampicin, carbamazepine, barbiturates and St John’s Wort) are not allowed for 2 weeks prior to randomisation or while

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to assess the efficacy of ZD6474 (100 mg and 300 mg) in combination with the modified FOLFOX 6 regimen (mFOLFOX6) versus mFOLFOX6 alone for the treatment of patients with colorectal cancer that have failed prior treatment with irinotecan and a fluoropyrimidine by assessment of disease progression.;Secondary Objective: The secondary objectives of the study are to assess the safety and tolerability of ZD6474 (100 mg and 300 mg) in combination with mFOLFOX6 in the treatment of colorectal cancer by review of AEs and laboratory parameters.;Primary end point(s): Assess efficacy of ZD6474 (100mg and 300mg) in combination with mFOLFOX6 versus mFOLFOX6 alone in the treatment of colorectal cancer.