Condition category
Cancer
Date applied
26/09/2012
Date assigned
26/09/2012
Last edited
05/12/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Ms Rachel Todd

ORCID ID

Contact details

Institute of Cancer Research Clinical Trials & Statistics Unit (ICR-CTSU)
Section of Clinical Trials
Sir Richard Doll Building
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
-
apredict-icrctsu@icr.ac.uk

Additional identifiers

EudraCT number

2011-004562-16

ClinicalTrials.gov number

Protocol/serial number

12404

Study information

Scientific title

A Phase II study of axitinib in patients with metastatic renal cell cancer unsuitable for nephrectomy

Acronym

A-PREDICT

Study hypothesis

A-PREDICT is a single arm, single agent, open label, multicentre, phase II study of axitinib in patients with metastatic renal cell carcinoma of predominant clear cell histology and unsuitable for debulking nephrectomy (as judged by the treating clinician).

Patients who have provided consent and have satisfied the eligibility criteria will be registered into the trial. The starting dose of axitinib will be 5 mg twice daily by mouth, escalating to a maximum of 10mg twice daily by mouth according to tolerability of treatment, for as long as patients are deriving clinical benefit. Treatment will be paused for one week prior to the week 9 biopsy. Disease progression will be evaluated according to RECIST v1.1 criteria 8 weeks after commencing treatment, at 8 weekly intervals to 6 months and 3 monthly thereafter. Blood and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. Nephrectomy will be carried out on any patient who becomes suitable in the opinion of the treating clinician during the course of the trial. Where possible, tissue samples will be taken from resected specimens. Response to axitinib in marker lesions will be correlated with changes in biomarkers.

Ethics approval

First MREC, 08/05/2012 ref: 12/LO/0639

Study design

Non-randomised interventional trial

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Renal cancer

Intervention

Oral axitinib twice a day. 5mg starting dose escalated to maximum of 10mg until disease progression

Intervention type

Drug

Phase

Phase II

Drug names

Axitinib

Primary outcome measures

Freedom from progression at 6 months, measured at 6 months after start of treatment

Secondary outcome measures

No secondary outcome measures

Overall trial start date

28/09/2012

Overall trial end date

27/09/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology
2. Unsuitable for nephrectomy as judged by treating clinician(s)
3. Not suitable for ‘watch and wait’ policy as determined by treating clinician(s)
4. No prior systemic therapy for renal cell carcinoma
5. Measurable metastatic disease using RECIST v1.1
6. 18 years of age or older
7. Life expectancy of 12 weeks or greater
8. ECOG performance status 0 or 1
9. Adequate organ function as defined by serum aspartate transaminase (AST) and serum alanine transaminase (ALT) =2.5 x upper limit of normal (ULN), or AST and ALT =5 x ULN if liver function abnormalities are due to liver metastases; total serum bilirubin =1.5 x ULN
10. Adequate haematological function as defined by absolute neutrophil count (ANC) =1500/µL, platelets =75,000/µL, haemoglobin =9.0 g/dL and prothrombin time (PT) =1.5 x ULN
11. Serum creatinine =1.5 x ULN or calculated creatinine clearance = 60 mL/min;
12. Urinary protein <2+ by urine dipstick. If dipstick is =2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2g per 24 hours.
13. No evidence of pre-existing uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be =140 mm Hg, and the baseline diastolic blood pressure readings must be =90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
14. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
15. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including tumour biopsies.
16. Written informed consent
17 Male or female participants

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 99

Participant exclusion criteria

1. The presence of intracranial disease, unless there has been radiological evidence of stable intracranial disease >6 months. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months postsurgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days.
2. The presence of active second malignancy. Patients will be eligible if they have adequately treated basal cell carcinoma, squamous cell skin cancer, in situ cervical cancer, stable prostate cancer or if treated with curative intent for any other cancer with no evidence of disease for 2 years.
3. Women who are pregnant or are breastfeeding. Female patients must be surgically sterile, be postmenopausal, or must agree to use effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrolment.
4. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
5. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC.
6. Gastrointestinal abnormalities including:
6.1. Inability to take oral medication
6.2. Requirement for intravenous alimentation
6.3. Prior surgical procedures affecting absorption including total gastric resection
6.4. Treatment for active peptic ulcer disease in the past 6 months
6.5. Active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;
6.6. Malabsorption syndromes.
7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors
8. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers
9. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access device or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
10. Active seizure disorder, spinal cord compression, or carcinomatous meningitis.
11. Any of the following within 12 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
12. Deep vein thrombosis or pulmonary embolism within 6 months prior to study entry.
13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

Recruitment start date

28/09/2012

Recruitment end date

27/09/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Institute of Cancer Researc Clinical Trials & Statistics Unit (ICR-CTSU)
Sutton
SM2 5NG
United Kingdom

Sponsor information

Organisation

Institute of Cancer Research (UK)

Sponsor details

Experimental Cancer Medicine Centre
Cancer Research
123 Old Brompton Road
London
SW7 3RP
United Kingdom

Sponsor type

Research organisation

Website

http://www.icr.ac.uk/

Funders

Funder type

Industry

Funder name

Pfizer UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes