Study of Axitinib for Reducing Extent of Venous Tumour Thrombus in Renal Cancer With Venous Invasion (NAXIVA)
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|ClinicalTrials.gov Identifier: NCT03494816|
Recruitment Status : Completed
First Posted : April 11, 2018
Results First Posted : June 30, 2021
Last Update Posted : June 30, 2021
NAXIVA is a study of axitinib in patients with metastatic and non-metastatic renal cell carcinoma with venous invasion. Patients will be given axitinib (twice daily) for 8 weeks (at an escalated dose) and the response of the venous invasion will be assessed.
Blood, urine and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response.
The primary objective is to assess the response of the thrombus to axitinib. Its thought that axitinib will reduce the extent of the thrombus in the inferior vena cava will reduce the extent of surgical intervention.
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma Metastatic Renal Cell Carcinoma Non-metastatic Renal Cell Carcinoma||Drug: Axitinib Oral Tablet||Phase 2|
NAXIVA is a single arm, single agent, open label, phase II feasibility study of axitinib in patients with both metastatic and non-metastatic renal cell carcinoma of clear cell histology. 20 patients will be recruited from multiple centres within the United Kingdom.
Patients who have signed informed consent and who have met all eligibility criteria will be registered into the trial.
The starting dose of axitinib will be 5mg BID and escalated to 7mg BID and then 10mg BID. A dose modification assessment will take place every 2 weeks in clinic during the 8 week pre-surgical treatment period and will be dependent on tolerability of treatment. Patients will follow an aggressive axitinib dose escalation process within the 8 week period to a maximum of 10mg BID. Patients should stop axitinib a minimum of 36 hours and a maximum of 7 days prior to surgery in week 9.
Blood, urine and tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. Nephrectomy and IVC tumour thrombectomy will be planned for all patients on the trial.
Response to axitinib in VTT, primary tumour and any RECIST measureable lesion will be correlated with changes in molecular markers.
Patients will be followed up in clinic at 6 & 12 weeks post surgery.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||NAXIVA- Phase II Neoadjuvant Study of Axitinib for Reducing Extent of Venous Tumour Thrombus in Clear Cell Renal Cell Cancer With Venous Invasion|
|Actual Study Start Date :||December 15, 2017|
|Actual Primary Completion Date :||March 3, 2020|
|Actual Study Completion Date :||June 10, 2020|
Axitinib - oral tablet twice daily for 8 weeks prior to surgery. Starting dose 5mg.
Drug: Axitinib Oral Tablet
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 and blood pressure.
Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day with or without food as per instruction. On clinic days only, patients will be advised to fast for 6 hours prior to their clinic visit.
Patients should be advised to stop axitinib treatment a minimum of 36 hours and maximum of 7 days prior to week 9 nephrectomy and thrombectomy surgery.
Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
- Number of Patients With a Change in Mayo Classification [ Time Frame: Surgery and radiology assessment at week 9 in comparison to pre-axitinib assessment. ]
The number and percentage of evaluable patients with a change in the Mayo Classification. A patient is defined as a responder if their Mayo level is lower at 9 weeks as compared to baseline; all other patients are defined as non-responders.
The Mayo Classification levels are defined as follows, ordered by increasing severity:
- Level 0: thrombus limited to the renal vein
- Level 1: into IVC <2cm from renal vein ostium level
- Level 2: IVC extension >2cm from renal vein ostium and below hepatic vein
- Level 3: thrombus at the level of or above the hepatic veins but below the diaphragm
- Level 4: thrombus extending above the diaphragm
- % Patients With Change in Surgical Management [ Time Frame: Surgical planning will be conducted at week 1 (prior to axitinib) and compared to the actual outcome at week 9. ]
The percentage of patients with a change in surgical management.
Tumour thrombus surgical management approaches are provided below, ordered by increasing invasiveness:
- Thrombus - Milked back into renal vein and side clamped
- Infra-hepatic (IVC clamping with no liver mobilisation)
- Retro-hepatic (liver mobilisation and clamping below hepatic veins)
- Retro-hepatic (liver mobilisation and clamping above hepatic veins)
- Supra-hepatic (infradiaphragmatic)
- Supra-hepatic (supradiaphragmatic)
- Change in Venous Tumour Thrombus (VTT) Height [ Time Frame: Radiology assessment- The VTT height will be measured prior to axitinib and compared with the VTT height just before surgery (week 9). Both pre-axitinib and week 9 scans will be centrally reviewed by the lead NAXIVA radiologists prior to analysis. ]The percentage change in VTT height. VTT height is measured as follows: if the size of the tumour is X at baseline and Y at the later timepoint, the reduction value is calculated as follows: 1-(Y/X). Therefore, positive values indicate a reduction and negative values indicate an increase.
- Number of Patients With RECIST Responses [ Time Frame: Radiology assessment- The response rate (RECIST) will be assessed at week 9 in comparison to pre-axitinib measurements.Both pre-axitinib and week 9 scans will be centrally reviewed by the lead NAXIVA radiologists prior to analysis. ]
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI.
In summary, the RECIST v1.1 response categories are:
- Complete Response (CR): disappearance of all target lesions
- Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions
- Progressive Disease (PD): >=20% increase in the sum of diameters of target lesions AND an absolute increase of >5mm (or the appearence of 1+ new lesions)
- Stable Disease (SD): neither sufficient shrinkage to for PR nor sufficient increase for PD Eisenhauer et al., 2009. Eur J Cancer; 45(2): 228-47.
- Surgical Complication Rates [ Time Frame: Morbidity rates will be assessed by radiology assessment using pre-axitinib and week 9 scans. Both pre-axitinib and week 9 scans will be centrally reviewed by the lead NAXIVA radiologists prior to analysis. ]
Morbidity will be measured according to the Clavien-Dindo classification.
A summary of the relevant categories is as follows:
Grade I: Any deviation from the normal post-operative course not requiring surgical, endoscopic or radiological intervention (inc. certain drugs, physiotherapy and wound infections that are opened at the bedside) Grade II: Complications requiring drug treatments other than those allowed for Grade I complications (inc. blood transfusion and total parenteral nutrition (TPN)) Grade III: Complications requiring surgical, endoscopic or radiological intervention (IIIa=not under general anaesthetic/IIIb=under general anaesthetic) Grade IV: Life-threatening complications (inc. CNS complications requiring intensive care, but excludes transient ischaemic attacks (TIAs)) (IVa=single-organ dysfunction (inc. dialysis)/IVb=multi-organ dysfunction) Grade V: Death of the patient Dindo et al., 2004. Ann Surg;240(2):205-13.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03494816
|Chelmsford, Essex, United Kingdom, CM1 7ET|
|Cambridge, United Kingdom, CB2 0QQ|
|Western General Hospital|
|Edinburgh, United Kingdom, EH4 2XU|
|Beatson West of Scotland Cancer Centre|
|Glasgow, United Kingdom, G12 0YN|
|Royal Free Hospital|
|London, United Kingdom, NW3 2QG|
|St George's Hospital|
|London, United Kingdom, SW17 0QT|
|London, United Kingdom, SW3 6JJ|
|Principal Investigator:||Grant D Stewart||University of Cambridge|