A Phase II, Randomised, Factorial, Double-blind Study to Investigate the Management of AZD2171-induced Hypertension and Efficacy of AZD2171 at Doses of 30 mg and 45 mg in Patients with Advanced Solid Tumours

Phase 1

• Conditions: Management of AZD2171-induced hypertension in patients with advanced solid tumours

• Registration Number: EUCTR2005-003442-33-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2005-11-07
• Last Update Posted: 3 November 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Provision of written informed consent.

2. Males or females aged 18 years and older.

3. Histological or cytological confirmation of advanced solid tumour (with the exception of prostate cancer), which is refractory to standard therapies or for which no standard therapy exists and for which there is a rationale for the therapeutic use of a VEGFR tyrosine kinase inhibitor.

4. World Health Organisation (WHO) Performance score 0-2.

5. Life expectancy of >12 weeks.

6. One or more measurable lesions at least 10 mm in the longest diameter by spiral computed tomography (CT) scan or 20 mm with conventional techniques (as defined by RECIST).

7. Patients considered by the investigator to be suitable for orally administered treatment.

For inclusion in the genetic research component of the study, patients must fulfil the following criterion:

1. Provision of informed consent for genetic research.

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. Untreated unstable brain or meningeal metastases. Patients with radiological evidence of stable brain metastases are eligible providing that they are asymptomatic and either:
a. do not require corticosteroids or
b. have been treated with corticosteroids, with clinical and radiological evidence of brain metastases stabilisation at least 10 days after discontinuation of steroids.

2. Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count <1.5 x 109/L or platelet count <100 x 109/L or requiring regular blood transfusions to maintain haemoglobin >9 g/dL.

3. Serum bilirubin >1.5 x upper limit of reference range (ULRR).

4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x ULRR. If liver metastases are present, ALT or AST >5 x ULRR.

5. Serum creatinine >1.5 x ULRR or a creatinine clearance of <50mL/min calculated by Cockcroft-Gault.

6. Greater than +1 proteinuria on 2 consecutive dipsticks taken no less than 1 week apart unless urinary protein <1.5 g in a 24-hour urine collection.

7. Patients with a history of poorly controlled hypertension with resting BP >150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy. Measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2 minute intervals and averaged. If the first 2 diastolic readings differ by more than 5 mmHg then an additional reading should be obtained, and averaged.

8. Patients who are currently receiving maximal doses of calcium-channel blockers or more than 1 anti-hypertensive for the treatment of hypertension.

9. Any evidence of severe or uncontrolled systemic diseases (eg, unstable or uncompensated respiratory, cardiac including arrhythmias, hepatic or renal disease), including known infection with Hepatitis B or C virus or human immunodeficiency virus.

10. Unresolved toxicity >CTC grade 2 from previous anti-cancer therapy except alopecia (if applicable).

11. Mean QTc with Bazett’s correction >470 msec in screening electrocardiogram (ECG) or history of familial long QT syndrome (as per International Conference on Harmonisation [ICH] guideline E14).

12. Significant haemorrhage (>30 ml bleeding/episode in previous 3 months) or haemoptysis (>5 ml fresh blood in previous 4 weeks).

13. Recent (<14 days) major surgery prior to entry into the study, or a surgical incision that is not fully healed.

14. Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication.

15. Known severe hypersensitivity to AZD2171 or any of its excipients.

16. Other concomitant anti-cancer therapy (including luteinising hormone releasing hormone agonists), except steroids.

17. Known severe hypersensitivity to beta-blockers or calcium-channel blockers.

18. History of other malignancies within 5 years except for adequately treated basal or squamous cell cancer or carcinoma in situ.

19. History of CNS disorders or uncontrolled seizures.

20. History of significant gastrointestinal impairment, as judged by the investigator that would significantly affect the absorption of AZD2171.

21. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at the study site).

22. Previous enrolment or randomisation of treatment in the present study.

23. Participation in an investigational drug trial within 30 days prior to starting AZD2171

Study & Design

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