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

ISRCTN	ISRCTN72679844
DOI	https://doi.org/10.1186/ISRCTN72679844
EudraCT/CTIS number	2011-004562-16
IRAS number	98117
ClinicalTrials.gov number	NCT01693822
Secondary identifying numbers	12404, IRAS 98117

Submission date: 26/09/2012
Registration date: 26/09/2012
Last edited: 18/12/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-axitinib-kidney-cancer-spread-a-predict

Study website

Contact information

Ms Rebecca Lewis
Scientific

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

Email	apredict-icrctsu@icr.ac.uk

Study information

Study design	Non-randomised interventional trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	A Phase II study of axitinib in patients with metastatic renal cell cancer unsuitable for nephrectomy
Study 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(s)	First MREC, 08/05/2012 ref: 12/LO/0639
Condition	Renal cancer
Intervention	Oral axitinib twice a day. 5mg starting dose escalated to maximum of 10mg until disease progression
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Axitinib
Primary outcome measure	Freedom from progression at 6 months, measured at 6 months after start of treatment
Secondary outcome measures	No secondary outcome measures
Overall study start date	28/09/2012
Overall study end date	28/02/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	UK Sample Size: 99
Total final enrolment	65
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 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

England
United Kingdom

Study participating centre

Institute of Cancer Researc Clinical Trials & Statistics Unit (ICR-CTSU)

Sutton
SM2 5NG
United Kingdom

Sponsor information

Institute of Cancer Research (UK)
Research organisation

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

Website	http://www.icr.ac.uk/
"ROR"	https://ror.org/043jzw605

Funders

Funder type

Industry

Pfizer UK
Private sector organisation / For-profit companies (industry)

Alternative name(s): Pfizer Ltd, Pfizer Limited
Location: United Kingdom

Results and Publications

Intention to publish date	30/06/2025
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer-reviewed journal
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Rebecca Lewis (apredict-icrctsu@icr.ac.uk). Clinical data are available for sharing subject to completion of a data sharing application form, approval by the trial oversight committees and completion of a data sharing agreement. As part of the review the trialists would consider whether the existing trial consent covers the application, what anonymisation will be required and whether separate ethics approval would be required.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results			26/10/2022	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

18/12/2024: The intention to publish date was changed from 31/12/2024 to 30/06/2025.
11/03/2024: IRAS number added. The intention to publish date was changed from 30/06/2024 to 31/12/2024.
10/08/2023: The intention to publish date was changed from 28/02/2023 to 30/06/2024.
27/02/2023: The trial website was added.
25/10/2022: Cancer Research UK plain English results link added.
02/08/2022: The following changes were made to the trial record:
1. The overall trial end date was changed from 27/09/2014 to 28/02/2022.
2. Total final enrolment, publication and dissemination plan, intention to publish date and IPD sharing statement added.
3. Contact details updated.
29/08/2019: ClinicalTrials.gov number added.