Condition category
Cancer
Date applied
13/02/2017
Date assigned
01/03/2017
Last edited
14/05/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Mrs Niki Couper

ORCID ID

Contact details

Scottish Clinical Trials Research Unit
Information Services Division
NHS National Services Scotland
Gyle Square
1 South Gyle Crescent
Edinburgh
EH12 9EB
United Kingdom

Type

Scientific

Additional contact

Dr Grant Stewart

ORCID ID

http://orcid.org/0000-0003-3188-9140

Contact details

Academic Urology Group
University of Cambridge
Box 43
Addenbrooke's Hospital
Cambridge Biomedical Campus
Hill's Road
Cambridge
CB2 0QQ
United Kingdom

Additional identifiers

EudraCT number

2017-000619-17

ClinicalTrials.gov number

Protocol/serial number

NAXIVA 1.2 (22/09/2017)

Study information

Scientific title

Phase II neoadjuvant study of Axitinib for reducing extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion

Acronym

NAXIVA

Study hypothesis

A reduction in the extent of the venous tumour thrombus, as assessed by the Mayo classification, will potentially result in less extensive and less morbid surgical approach with immediate patient benefits of reduced operative mortality/morbidity, potential shorter hospital stay and shorter recuperation period to return to full activities of daily living.

Ethics approval

East of England – Cambridgeshire and Hertfordshire Ethics Committee, 02/08/2017.

Study design

Single-arm single-agent open label phase II feasibility study

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 contact details to request a participant information sheet.

Condition

Clear cell renal cell cancer with venous thrombus invasion

Intervention

All participants will receive an 8 week course of Axitinib. Patients will be followed up every 2 weeks from day 1, week 1 of receiving Inlyta. All patients will start at 5mg BID with possible escalation to 7mg BID and the max 10mg BID. Only if no adverse events related to study drug above CTCAE grade 2 for a consecutive 2-week period the patient may have their dose increased by one dose level to a maximum of 10 mg BID. Patients will be given a 2 week supply at each follow up visit of Inlyta (oral tablet) to be taken twice daily as per instructed.

Intervention type

Drug

Phase

Phase II

Drug names

Axitinib

Primary outcome measures

Thrombus invasion will be measured using MRI scanning according to the Mayo classification at baseline and pre-surgery (week 9).

Secondary outcome measures

Current secondary outcome measures as of 23/04/2018:
1. Percentage change in surgical approach (to a less invasive surgical approach) as assessed by review of MRI scans by surgeons at baseline and week 9 (i.e after axitinib therapy has been completed)
2. Percentage change in height of the cancer invasion into the large blood vessels draining the kidney (venous tumour thrombus). This will be evaluated by comparing baseline and week 9 scans. Local radiologists will conduct the evaluation and a central radiology review will be conducted.
3. Objective tumour response rate measured by MRI/CT scans at baseline and week 9.
4. Complications of surgery (i.e. blood loss and need for a blood transfusion) assessed according to the Clavien-Dindo classification of surgical complications at baseline and week 9

Previous secondary outcome measures
1. Percentage change in surgical approach is assessed by review of MRI scans by surgeons at baseline and 9 weeks
2. Percentage change in height of the venous tumour thrombus will be evaluated by comparing baseline and week 9 scans. Local Radiologists will conduct the evaluation and a central radiology review will be conducted.
3. The response rate (RECIST) will be measured by MRI/CT at baseline and week 9
4. Change in Inferior vena cava- tumour thrombus volume will be assessed by radiologists comparing CT/MRI scans taken at baseline and week 9
5. Morbidity will be measured using MRI/CT scanning according to the Clavien-Dindo classification at baseline and week 9

Overall trial start date

01/03/2017

Overall trial end date

01/01/2020

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 23/04/2018:
1. Aged 18 years and over
2. Biopsy-proven clear cell RCC
3. Immediate resection of the primary tumour considered technically possible
4. The patient must be suitable for and willing to undergo nephrectomy surgery
5. The clinical (radiologically determined) stage of the tumour must be into the main renal vein (cT3a, but seen in the main branch of the renal vein leading to but not beyond the vein ostium with the inferior vena cava (IVC)), or the IVC itself either below of above the diaphragm (cT3b or cT3c respectively)
6. Nodal status may be clinically node negative (cN0) on CT, indeterminate (cNx) or clinically node positive on CT (cN1)
7. Non-metastatic (M0) and metastatic (M1) clear cell renal cell patients
8. The patient must have an ECOG performance status of either 0 or 1
9. Urine must contain less than 2 g protein. If urine contains ≥2 g then a 24-h urine collection should be performed and the patient may enter if urinary protein is <2 g per 24 hours.
10. All female patients with reproductive potential must have a negative serum or urine pregnancy test within a maximum of 14 days prior to starting trial treatment.

Previous inclusion criteria:
1. Aged 18 years and over
2. Biopsy proven clear cell RCC
3. Resectable Tumour
4. The clinical (radiologically determined) stage of the tumour must be into the main renal vein (cT3a, but seen in the main branch of the renal vein leading to but not beyond the vein ostium with the inferior vena cava (IVC)), or the IVC itself either below of above the diaphragm (cT3b or cT3c respectively)
5. Nodal status may be clinically node negative (cN0) on CT, indeterminate (cNx) or clinically node positive on CT (cN1)
6. Non-metastatic (M0) and Metastatic (M1) clear cell renal cell patients
7. Stratification by the Mayo classification

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

20 patients will be recruited over a 24 month period in 6-8 sites across the UK.

Participant exclusion criteria

Current exclusion criteria as of 23/04/2018:
1. Metastatic patients with poor risk on the Memorial Sloan Kettering Cancer Centre (MSKCC) score and deemed suitable for cytoreductive nephrectomy at time of enrolment
2. 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. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
4. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC
5. Gastrointestinal abnormalities including:
5.1. Inability to take oral medication
5.2. Requirement for intravenous alimentation
5.3. Prior surgical procedures affecting absorption including total gastric resection
5.4. Treatment for active peptic ulcer disease in the past 6 months
5.5. 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
5.6. Malabsorption syndromes
6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy)
7. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, concomitant therapy)
8. 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.
9. Active seizure disorder, spinal cord compression, or carcinomatous meningitis
10. Any of the following within 12 months prior to study entry:
10.1 myocardial infarction
10.2 uncontrolled angina
10.3 coronary/peripheral artery bypass graft
10.4 symptomatic congestive heart failure
10.5 cerebrovascular accident or transient ischemic attack
11. Uncontrolled hypertension (>160/100 mmHg despite optimised antihypertensive treatment)
12. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
13. ALT or AST ≥1.5 x upper limit of normal; Bilirubin ≥1.5 x upper limit of normal
14. Serum creatinine ≥1.5 x upper limit of normal
15. Neutrophil count <1.0 x 10(9)/l; platelet count <100 x 10(9)/l; Hb ≤90 g/l
16. Known severe hepatic impairment (Child-Pugh class C)
17. Known hypersensitivity to axitinib or any of its excipients. Specifically patients with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not enter the study.


Previous exclusion criteria
1. 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.
2. 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 enrollment.
3. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy
4. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC.
5. Gastrointestinal abnormalities including:
5.1. Inability to take oral medication
5.2. Requirement for intravenous alimentation
5.3. Prior surgical procedures affecting absorption including total gastric resection
5.4. Treatment for active peptic ulcer disease in the past 6 months
5.5. 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
5.6. Malabsorption syndromes
6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy)
7. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, concomitant therapy)
8. 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.
9. Active seizure disorder, spinal cord compression, or carcinomatous meningitis
10. 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
11. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness

Recruitment start date

01/12/2017

Recruitment end date

30/11/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Addenbrooke's Hospital
Cambridge Biomedical Campus Hill's Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Trial participating centre

Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Christie Hospital
550 Wilmslow Road
Manchester
M20 4BX
United Kingdom

Trial participating centre

Royal Marsden
Fulham Road
London
SW3 6JJ
United Kingdom

Trial participating centre

St George's Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom

Sponsor information

Organisation

Common Services Agency

Sponsor details

Strategic Business Unit
Public Health and Intelligence (Information Services Division)
Gyle Square
South Gyle Crescent
Edinburgh
EH12 9EB
United Kingdom

Sponsor type

Government

Website

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

Planned publication in a high-impact peer review journal.

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/07/2021

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

14/05/2018: Cancer Research UK lay summary link added to plain English summary field 23/04/2018: The following changes have been made following changes to the trial design associated with REC and MHRA review: 1. The protocol number has been changed from NAXIVA 1.0 to NAXIVA 1.2 (22/09/2017) 2. Ethics approval information has been added. 3. The secondary outcome measures have been changed. 4. The participant inclusion criteria have been changed. 5. The participant exclusion criteria have been changed. 6. The recruitment start date has been changed from 30/09/2017 to 01/12/2017. 7. The recruitment end date has been changed from 01/10/2019 to 30/11/2019. 16/01/2018: Internal review. 16/10/2017: Internal review.