A study of pazopanib efficacy and safety in patients with advanced clear-cell renal cell carcinoma and ECOG Performance Status 2 (PaZ02)

ISRCTN	ISRCTN38957238
DOI	https://doi.org/10.1186/ISRCTN38957238
EudraCT/CTIS number	2011-001211-31
Secondary identifying numbers	11827

Submission date: 29/03/2012
Registration date: 29/03/2012
Last edited: 23/10/2020

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-advanced-kidney-cancer

Study website

Contact information

Dr Leyre Navarro-Nuñez
Scientific

PaZ02 trials office
Cancer Research UK Clinical Trials Unit (CRCTU)
School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Phone	+44 (0) 121 414 7671
Email	pazo2@trials.bham.ac.uk

Study information

Study design	Early phase II non-randomised single arm multicentre study
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available, trial now closed to recruitment
Scientific title	A study of PaZopanib efficacy and safety in patients with advanced clear-cell renal cell carcinoma and ECOG Performance Status 2 (PaZ02): A non-randomised phase II trial
Study acronym	PaZ02
Study objectives	New treatments which are active and well tolerated are needed for patients with advanced renal cancer who suffer from symptoms that are bad enough to affect their quality of life and ability to carry on with their daily routine. These patients are classed as 'Performance Status 2'. The objective of this study is to see if a new drug called pazopanib can prevent the renal cancer from growing and see if it is well tolerated by patients with advanced renal cancer who are classed as 'Performance Status 2'. Pazopanib works by disrupting the capillaries and blood vessels which supply the tumour tissue with blood and nutrients. In previous clinical trials pazopanib has demonstrated a significant effectiveness in advanced renal cell cancer patients who are less affected by their symptoms and is currently used for their treatment. It has not yet been tested in patients with 'Performance Status 2'.
Ethics approval(s)	East Midlands - Nottingham 2 Committee First MREC approval date 24th February 2012, ref: 11/EM/0450
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Renal Cancer; Disease: Kidney
Intervention	Pazopanib, Patients will receive pazopanib 800 mg once daily (OD) orally continuous dosing.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Pazopanib
Primary outcome measure	Current primary outcome measures as of 05/02/2019: 1. Tolerability: proportion of patients at 6 months of treatment who were free from drug-related grade 3-4 toxicities resulting in an SAE or drug discontinuation >3 weeks. 2. Efficacy: Proportion of patients progression free (as per RECIST guidelines version 1.1) and alive at 6 months. Previous primary outcome measures: Efficacy and tolerability 1. Efficacy: proportion of patients who are progression free and alive at 6 months 2. Tolerability: Ratio of patients free of grade 3, grade 4 adverse events which are related to the study medication and deemed to be clinically relevant
Secondary outcome measures	Current secondary outcome measures as of 05/02/2019: 1. Overall Survival (OS) - will be measured at 12 months post registration as the number of whole days from date of entry into the trial until death by any cause or censor. 2. Progression Free Survival (PFS) - will be measured at 12 months post registration as the number of whole days from the date of entry into trial until evidence of radiological disease progression or death by any cause, or censor date. 3. Response and clinical benefit rates - Response Rate will be defined as the proportion of patients who achieve either a complete or partial Radiological Response and Clinical benefit rate will be defined as the proportion of patients who achieve either a complete, partial or stable radiological response as defined by the RECIST 1.1 Criteria. 4. Duration of response - will be measured as the number of whole days between date of first evidence of response (CR or PR) until date of Progression of the Disease (PD) or death as defined by the RECIST1.1 Criteria. 5. Treatment safety - defined as the proportion of patients developing Adverse Events (AEs). AEs will be collected from the date of entry in the trial until 28 days after drug discontinuation and graded according the NCI-CTC version 4. AEs will be classified by causality, grade, type, duration and system involved. 6. Drug dose administered - defined by dose intensity, incidences of dose reductions, interruptions, escalations and discontinuations. Previous secondary outcome measures as of 05/02/2019: 1. Overall Survival (OS) 2. Progression Free Survival (PFS) 3. Response and clinical benefit rates 4. Duration of response 5. Treatment safety 6. Drug dose administered Previous secondary outcome measures: 1. Overall survival 2. Progression Free Survival (PFS) 3. Response and clinical benefit rates 4. Duration of response 5. Treatment safety dose
Overall study start date	01/04/2011
Completion date	31/12/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 75; UK Sample Size: 75
Total final enrolment	75
Key inclusion criteria	1. Written informed consent 2. Histologically confirmed diagnosis of renal cell carcinoma with clear cell component 3. Locally advanced (defined as not amenable of curative surgery) or metastatic disease 4. Measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) Criteria 1.1 5. Performance Status 2 assessed using the ECOG scale 6. No prior systemic therapy 7. Female patients of childbearing potential will be eligible if they agree to adequate contraception. Pregnancy test must be negative 1 week before first drug dose 8. Adequate organ function as defined by the following criteria: 8.1. Total serum bilirubin ≤1.5 x upper limit normal (ULN). Patients with Gilberts disease are eligible if the total bilirubin is <3.0 x ULN and direct bilirubin is ≤ 35%. 8.2. Serum transaminases (AST and ALT) <2.5 x ULN, unless liver metastases are documented in which case AST and ALT must be ≤ 5 x ULN 8.3. Calculated creatinine clearance ≥ 30mL/min (Cockroft Gault method) 8.4. Urine Protein to Creatinine Ratio (UPC) < 1. If UPC ≥ 1 then a 24 hour urine protein must be assessed. Only patients with 24 hour urine protein < 1g will be eligible 8.5. Total serum calcium concentration < 2.9 mmol/l 8.6. Absolute neutrophil count (ANC) ≥ 1500/mm3 8.7. Haemoglobin ≥ 9g/dl 8.9. Platelets ≥ 100,000/mm3 8.10. INR (International Normalised ratio) ≤ 1.2 x ULN. Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range 9. Age ≥18 10. Life expectancy ≥ 12 weeks 11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
Key exclusion criteria	1. Pregnant or lactating female patients. Patients who agree to discontinue nursing 14 days prior to commencing treatment and do not nurse throughout all the treatment period are eligible 2. Previous systemic treatment for renal cell carcinoma (RCC) (licensed or investigational) including adjuvant or neoadjuvant therapy 3. Major surgery or trauma < 4 weeks or radiotherapy and/or presence of any nonhealing wound, fracture, or ulcer. Radiotherapy < 2 weeks prior to starting treatment 4. History or clinical evidence of brain metastases or active seizure disorders 5. Previous malignancies within the last 5 years, with the exception of successfully treated superficial or in situ carcinomas and of invasive tumours treated with curative intent and in remission for at least 5 years 6. Current use of drugs which are known strong CYP4A inhibitors (7.10) 7. Use of any prohibited medications within 14 days of the first dose of study medication ( 8. Uncontrolled hypertension defined as systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 95 mm Hg. Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry 9. Presence of uncontrolled infection 10. Prolongation of the QT interval (QTc) > 480 msecs 11. History of malabsorption, major gastrointestinal tract resection or other pathology likely to affect study drug absorption 12. History of any one or more of the following cardiovascular conditions within the past 6 months: 12.1. Cardiac angioplasty or stenting 12.2. Myocardial infarction 12.3. Unstable angina 12.4. Coronary artery bypass graft surgery 12.5. Symptomatic peripheral vascular disease 12.6. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) Functional Classification 13. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) within the past 12 months 14. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Patients with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible 15. Evidence of active bleeding or bleeding diathesis 16. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels 17. Any serious and/or unstable preexisting medical, psychiatric, or other conditions that could interfere with subjects safety, obtaining informed consent or compliance to the study 18. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drug chemically related to pazopanib
Date of first enrolment	21/02/2013
Date of final enrolment	12/08/2016

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

PaZ02 trials office

Birmingham
B15 2TT
United Kingdom

Sponsor information

University of Birmingham
University/education

Research Support Group
University of Birmingham
Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Website	https://www.birmingham.ac.uk
"ROR"	https://ror.org/03angcq70

Funders

Funder type

Industry

GlaxoSmithKline
Government organisation / For-profit companies (industry)

Alternative name(s): GlaxoSmithKline plc., GSK plc., GSK
Location: United Kingdom

Novartis
Government organisation / For-profit companies (industry)

Alternative name(s): Novartis AG, Novartis International AG
Location: Switzerland

Results and Publications

Intention to publish date	30/09/2020
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Results of this trial will be submitted for publication in a peer reviewed journal. The manuscript will be prepared by the Trial Management Group (TMG) and authorship will be determined by mutual agreement. Any secondary publications and presentations prepared by Investigators must be reviewed by the TMG. Manuscripts must be submitted to the TMG in a timely fashion and in advance of being submitted for publication, to allow time for review and resolution of any outstanding issues. Authors must acknowledge that the trial was performed with the support of University of Birmingham. Intellectual property rights will be addressed in the Clinical Study Site Agreement between Sponsor and site.
IPD sharing plan

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Abstract results	22/10/2018		No	No
Basic results	20/10/2020		No	No
HRA research summary		28/06/2023	No	No

Additional files

ISRCTN38957238_BasicResults_20Oct2020.pdf: Uploaded 23/20/2020

Editorial Notes

23/10/2020: The following changes have been made:
1. The basic results of this trial have been uploaded as an additional file.
2. An invalid url has been removed from the study hypothesis.
3. The study design has been changed from "Non-randomised; Interventional; Design type: Diagnosis, Prevention, Process of Care, Screening, Treatment" to "Early phase II non-randomised single arm multicentre study".
4. The sponsor website has been added.
5. The recruitment start date has been changed from 01/04/2011 to 21/02/2013.
11/12/2019: The following changes have been made:
1. The intention to publish date has been added.
2. The total final enrolment number has been added.
3. The Publication and dissemination plan has been added.
4. The Participant level data availability has been added.
06/02/2019: The secondary outcomes were updated.
05/02/2019: The following changes were made:
1. Link to Cancer Research UK plain English summary was changed.
2. Trial website link added.
3. The scientific contact has been changed from Dr Steve Johnson to Dr Leyre Navarro-Nuñez.
4. The link to more details in the hypothesis has been removed: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=11827
5. The participant information sheet was previously available on request, but is now not available.
6. The intervention type was changed to 'Drug', the phase changed to 'Phase II', and the drug name added: 'Pazopanib'.
7. The primary outcome measures have been changed.
8. The secondary outcome measures have been changed.
9. The overall trial end date was changed from 01/04/2013 to 31/12/2018.
10. The recruitment end date was changed from 01/04/2013 to 12/08/2016.
11. The sponsor's address was updated.
12. The funder name 'Novartis' was added.
13. A link to a conference abstract was added to the publications list.
09/05/2016: No publications found, study status unverified.