Clear-cell Metastatic Renal Cell CarcinomaPhase 2A-PREDICTNCT01693822
A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy
A Phase 2 study testing Axitinib in people with Clear-cell Metastatic Renal Cell Carcinoma, run by Institute of Cancer Research, United Kingdom at 11 sites in United Kingdom.
Trial summary
A-PREDICT is a study of axitinib in patients with metastatic renal cell carcinoma unsuitable for nephrectomy (as judged by the treating clinician) to evaluate efficacy, safety, toxicity and changes in biomarkers during therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clear-cell Metastatic Renal Cell Carcinoma
- What is being tested?
- Axitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 11 sitesUnited Kingdom
- Study dates
- Oct 2012to 28 Feb 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology
- Unsuitable for nephrectomy
- Unsuitable for 'watch and wait' policy
- No prior systemic therapy for renal cell carcinoma
- Measurable metastatic disease using RECIST v1.1
- Life expectancy 12 weeks or greater
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- ECOG performance status 0 or 1
- Adequate organ function as defined by serum aspartate transaminase (AST) or 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
- 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
- Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min;
- Urinary protein <2+ by urine dipstick.
- No evidence of pre-existing uncontrolled hypertension
- Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
- Willingness and ability to comply with study procedures, including tumour biopsies.
- Written informed consent
Who cannot join
- The presence of intracranial disease, unless stable >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 post-surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days.
- The presence of active second malignancy.
- 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.
- Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
- Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC.
- Gastrointestinal abnormalities including:
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- inability to take oral medication;
- requirement for intravenous alimentation;
- prior surgical procedures affecting absorption including total gastric resection;
- treatment for active peptic ulcer disease in the past 6 months;
- 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;
- malabsorption syndromes.
- Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy).
- Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, concomitant therapy).
- 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.
- Active seizure disorder, spinal cord compression, or carcinomatous meningitis.
- 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.
- Deep vein thrombosis or pulmonary embolism within 6 months prior to study entry.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
- Known galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United Kingdom11 sites
Addenbrooke's Hospital
Cambridge, CB2 0QQ
Western General Hospital
Edinburgh, EH4 2XU
Royal Surrey County Hospital
Guildford, Surrey, GU2 7XX
Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF
Royal Marsden Hospital - Sutton
London, Sutton, SM2 5PT
Royal Free Hospital
London, NW3 2QG
Guy's Hospital
London, Se1 9RT
Royal Marsden Hospital
London, SW3 6JJ
Christie Hospital
Manchester, M20 4BX
The Clatterbridge Cancer Centre NHS Foundation Trust
Metropolitan Borough of Wirral, CH63 4JY
Derriford Hospital
Plymouth, PL6 8DH
About this study
Official title: A-PREDICT: A Phase II Study Of Axitinib In Metastatic Renal Cell Cancer in Patients Unsuitable for Nephrectomy
A-PREDICT is a study of axitinib in patients with metastatic renal cell carcinoma unsuitable for nephrectomy (as judged by the treating clinician) to evaluate efficacy, safety, toxicity and changes in biomarkers during therapy. Axitinib will given twice daily by mouth according to tolerability of treatment, for as long as patients are deriving clinical benefit. Blood and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. The primary clinical objective of this study is to define the activity of axitinib given to patients with metastatic renal cell carcinoma unsuitable for nephrectomy.
Read the detailed description
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 percutaneous biopsy of the primary on day 1 week 9. 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.
- Being tested
- Axitinib
- Keywords
- metastatic renal cell carcinoma, predominant clear cell histology, Unsuitable for nephrectomy, unsuitable for 'watch and wait' policy
- Medical subject headings
- Clear-cell metastatic renal cell carcinoma, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AxitinibDrug
Also called AG-013736
Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities.
Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy.
Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day.
Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
| Study group | Role | What they receive |
|---|---|---|
| Axitinib | Experimental | Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Receives: Drug: Axitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Freedom From Progression at 6 Months
The proportion of study participants alive and progression free at 6 months (day 1 week 25 visit). Progression will be measured from the date of study entry (registration date) until the first date of either death or confirmed progressive disease according to RECIST v1.1 (https://recist.eortc.org/recist-1-1-2/). Patients alive and free from progression will be censored at the date of last follow-up. The proportion of patients progression free at 6 months will be reported with 95% confidence interval. In addition, progression free survival will be presented using the Kaplan Meier product limit method with median progression free survival reported. A blinded central review of CT scans will be conducted for verification purposes.
Measured: 6 months
Secondary outcomes (5)
Best Overall Response
Best overall response (one of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) throughout the treatment period according to RECIST v1.1 (https://recist.eortc.org/recist-1-1-2/).
Measured: From registration, during treatment and up to 30 days after treatment discontinuation. Patients remain on treatment until disease progression assessed up to 106 months.
Progression Free Survival
Progression-free survival (PFS) will be measured from the date of registration until first date of either death or confirmed progressive disease according to RECIST 1.1. Time to last follow-up will be used if patient has not progressed or died and PFS time for the patient will be considered censored. A Kaplan Meier graph and median survival time will be presented.
Measured: From the date of registration until first date of either death or confirmed progressive disease from any cause, whichever came first, assessed up to 106 months.
Overall Survival
Overall survival will be measured from the date of registration until the date of death due to any cause. Time to last follow-up will be used if patient has not died and survival time for the patient will be considered censored.
Measured: From the date of registration until the date of death due to any cause, up to 106 months.
Safety and Toxicity of Axitinib (by NCI CTC Grading Version 4)
Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Measured: Treatment duration (at least 4 weekly, and again at disease progression), up to 106 months.
Number of Patients Who Become Suitable for Nephrectomy as a Consequence of Therapy With Axitinib
The proportion of patients who undergo nephrectomy following registration as a result of treatment with axitinib will be reported with 95% confidence intervals.
Measured: Study duration (assessed by clinician over treatment duration), up to 106 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2012 (estimated)
- Study startOct 2012
- Primary completionMar 2017
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Clear-cell Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Institute of Cancer Research, United KingdomThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Cancer Research, United Kingdom
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Royal Marsden NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- James Larkin, Principal investigator, Royal Marsden Hospital London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01693822
- Sponsor's protocol ID
- ICR-CTSU/2011/10033
- Acronym
- A-PREDICT
- Status last verified
- Nov 2024
- First submitted
- 6 Aug 2012
- Last updated
- 21 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual participant data, together with a data dictionary defining each field in the set, will be made available to other researchers on request, subject to the approval of a formal data access request in accordance with the ICR-CTSU data and sample access policy. Trial documentation including the protocol are available on request by contacting apredict-icrctsu@icr.ac.uk Formal requests for data sharing are considered in line with ICR-CTSU procedures. Requests are via a standard proforma describing the nature of the proposed research and extent of data requirements. Contact apredict-icrctsu@icr.ac.uk or visit the link below for further information.
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A-PREDICT: A Phase II Study Of Axitinib In Metastatic Renal Cell Cancer in Patients Unsuitable for Nephrectomy
- ClinicalTrials.gov ID
- NCT01693822
- Acronym / sponsor ID
- A-PREDICT / ICR-CTSU/2011/10033
- Keywords
- metastatic renal cell carcinoma, predominant clear cell histology, Unsuitable for nephrectomy, unsuitable for 'watch and wait' policy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Institute of Cancer Research, United KingdomUniversity, hospital or other
- Collaborators
- Pfizer, Royal Marsden NHS Foundation Trust
- Study start
- Oct 2012
- Primary completion
- Mar 2017 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 26 Sep 2012 (estimated)
- Results
- Posted 21 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A-PREDICT is a study of axitinib in patients with metastatic renal cell carcinoma unsuitable for nephrectomy (as judged by the treating clinician) to evaluate efficacy, safety, toxicity and changes in biomarkers during therapy. Axitinib will given twice daily by mouth according to tolerability of treatment, for as long as patients are deriving clinical benefit. Blood and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. The primary clinical objective of this study is to define the activity of axitinib given to patients with metastatic renal cell carcinoma unsuitable for nephrectomy.
Detailed description
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 percutaneous biopsy of the primary on day 1 week 9. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Axitinib | Experimental | Drug: AxitinibAxitinib - oral tablet twice daily until disease progression. Starting dose 5mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology
- Unsuitable for nephrectomy
- Unsuitable for 'watch and wait' policy
- No prior systemic therapy for renal cell carcinoma
- Measurable metastatic disease using RECIST v1.1
Key exclusion criteria (20 listed)
- The presence of intracranial disease, unless stable >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 post-surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days.
- The presence of active second malignancy.
- 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.
- Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
- Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AxitinibAlso: AG-013736Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol. | Drug | Axitinib |
Primary outcome
Freedom From Progression at 6 Months
Time frame: 6 months
The proportion of study participants alive and progression free at 6 months (day 1 week 25 visit). Progression will be measured from the date of study entry (registration date) until the first date of either death or confirmed progressive disease according to RECIST v1.1 (https://recist.eortc.org/recist-1-1-2/). Patients alive and free from progression will be censored at the date of last follow-up. The proportion of patients progression free at 6 months will be reported with 95% confidence interval. In addition, progression free survival will be presented using the Kaplan Meier product limit method with median progression free survival reported. A blinded central review of CT scans will be conducted for verification purposes.
5 secondary outcomes
Best Overall Response
Time frame: From registration, during treatment and up to 30 days after treatment discontinuation. Patients remain on treatment until disease progression assessed up to 106 months.
Progression Free Survival
Time frame: From the date of registration until first date of either death or confirmed progressive disease from any cause, whichever came first, assessed up to 106 months.
Overall Survival
Time frame: From the date of registration until the date of death due to any cause, up to 106 months.
Safety and Toxicity of Axitinib (by NCI CTC Grading Version 4)
Time frame: Treatment duration (at least 4 weekly, and again at disease progression), up to 106 months.
Number of Patients Who Become Suitable for Nephrectomy as a Consequence of Therapy With Axitinib
Time frame: Study duration (assessed by clinician over treatment duration), up to 106 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified individual participant data, together with a data dictionary defining each field in the set, will be made available to other researchers on request, subject to the approval of a formal data access request in accordance with the ICR-CTSU data and sample access policy. Trial documentation including the protocol are available on request by contacting apredict-icrctsu@icr.ac.uk Formal requests for data sharing are considered in line with ICR-CTSU procedures. Requests are via a standard proforma describing the nature of the proposed research and extent of data requirements. Contact apredict-icrctsu@icr.ac.uk or visit the link below for further information.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Larkin principal investigator
Royal Marsden Hospital London
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Axitinib in people with Clear-cell Metastatic Renal Cell Carcinoma, run by Institute of Cancer Research, United Kingdom at 11 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Freedom From Progression at 6 Months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2024.