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Renal Cell CarcinomaPhase 2NAXIVANCT03494816

Study of Axitinib for Reducing Extent of Venous Tumour Thrombus in Renal Cancer With Venous Invasion

A Phase 2 study testing Axitinib Oral Tablet in people with Renal Cell Carcinoma and Metastatic Renal Cell Carcinoma, run by Scottish Clinical Trials Research Unit at 7 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Axitinib Oral Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
7 sitesUnited Kingdom
Study dates
15 Dec 2017to 10 Jun 2020
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

  • 1. Age ≥ 18. 2. Histologically proven clear cell RCC. 3. Immediate resection of the primary tumour considered technically possible. 4. Suitable for and willing to undergo nephrectomy (either cytoreductive or with curative intent) 4. cT3b, cT3c, cT3a (main renal vein) 5. N0, N1, or Nx 6. M0, or M1 7. ECOG performance status 0 - 1 8. Urinalysis <2+ protein. If dipstick is ≥2+ then a 24-hour urine collection should be performed and the patient may enter NAXIVA only if urinary protein is <2g per 24 hours.
  • 9. 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.

Who cannot join

  • For M1 patients: poor risk on Memorial Sloan Kettering Cancer Centre (MSKCC) score and deemed suitable for cytoreductive nephrectomy at time of enrolment.
  • 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. Patients with prostate cancer will be permitted entry if not receiving treatment and prostrate-specific antigen (PSA) is not rising.
  • 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 and up to 1 week after treatment.
  • Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy and for 6 months after completion of study drug (Patients who do not meet this will not be are not eligible).
  • Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine or pulmonary disease other than directly related to RCC.
  • Gastrointestinal abnormalities including: a. inability to take oral medication; b. requirement for intravenous alimentation; c. prior surgical procedures affecting absorption including total gastric resection; d. treatment for active peptic ulcer disease in the past 6 months; e. 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; f. malabsorption syndromes.
Show all 18Show fewer
  • Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 4.4, concomitant therapy).
  • Current use, or anticipated need for treatment with, drugs that are known CYP3A4 inducers or substrates for CYP1A2 (see section 4.4, 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.
  • Uncontrolled hypertension (>160/100 mmHg despite optimised antihypertensive treatment).
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
  • ALT or AST ≥ 1.5 x ULN; Bilirubin ≥ 1.5 x ULN.
  • Serum creatinine ≥ 1.5 x ULN
  • Neutrophil count < 1.0 x 109/L; platelet count < 100 x 109/L; Hb ≤ 90g/L.
  • Known severe hepatic impairment (Child-Pugh class C)
  • 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.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United Kingdom7 sites

  • Addenbrookes Hospital

    Cambridge, CB2 0QQ

  • Broomfield Hospital

    Chelmsford, Essex, CM1 7ET

  • Western General Hospital

    Edinburgh, EH4 2XU

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • Royal Free Hospital

    London, NW3 2QG

  • St George's Hospital

    London, SW17 0QT

  • Royal Marsden

    London, SW3 6JJ

Other trials in United Kingdom

About this study

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

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.

Read the detailed description

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.

Being tested
Axitinib Oral Tablet
Keywords
Neoadjuvant, Venous Tumour Thrombus, Axitinib, Mayo Classification, Nephrectomy, Thrombectomy
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Axitinib Oral TabletDrug

    Also called Inlyta, AG-013736

    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.

Study groups in NCT03494816
Study groupRoleWhat they receive
AxitinibExperimentalAxitinib - oral tablet twice daily for 8 weeks prior to surgery. Starting dose 5mg.
Receives: Drug: Axitinib Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With a Change in Mayo Classification

    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

    Measured: Surgery and radiology assessment at week 9 in comparison to pre-axitinib assessment.

Secondary outcomes (4)

  1. % Patients With Change in Surgical Management

    The percentage of patients with a change in surgical management.

    Tumour thrombus surgical management approaches are provided below, ordered by increasing invasiveness:

    1. Thrombus - Milked back into renal vein and side clamped
    2. Infra-hepatic (IVC clamping with no liver mobilisation)
    3. Retro-hepatic (liver mobilisation and clamping below hepatic veins)
    4. Retro-hepatic (liver mobilisation and clamping above hepatic veins)
    5. Supra-hepatic (infradiaphragmatic)
    6. Supra-hepatic (supradiaphragmatic)

    Measured: Surgical planning will be conducted at week 1 (prior to axitinib) and compared to the actual outcome at week 9.

  2. Change in Venous Tumour Thrombus (VTT) Height

    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.

    Measured: 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.

  3. Number of Patients With RECIST Responses

    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.

    Measured: 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.

  4. Surgical Complication Rates

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Apr 2018
  2. Study start15 Dec 2017
  3. Primary completion3 Mar 2020
  4. Study completion10 Jun 2020

Resources

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
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03494816
Sponsor's protocol ID
NAXIVA
Other IDs
2017-000619-17, ISRCTN96273644, 2017
Acronym
NAXIVA
Status last verified
Jun 2021
First submitted
3 Apr 2018
Last updated
30 Jun 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Re C, Ince WHJ, Bickley L, Blackmur JP, Ismail MH, Kyeremeh J, Kuusk T, Serrao EM, Jones JO, Stewart GD. Oligoprogressive renal cell carcinoma: What is the role of surgery? BJU Int. 2026 Aug;138(2):219-228. doi: 10.1111/bju.70281. Epub 2026 Apr 13.

    PubMed 41969229

  • Stewart GD, Welsh SJ, Ursprung S, Gallagher FA, Jones JO, Shields J, Smith CG, Mitchell TJ, Warren AY, Bex A, Boleti E, Carruthers J, Eisen T, Fife K, Hamid A, Laird A, Leung S, Malik J, Mendichovszky IA, Mumtaz F, Oades G, Priest AN, Riddick ACP, Venugopal B, Welsh M, Riddle K, Hopcroft LEM; NAXIVA Trial Group; Jones RJ. A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA). Br J Cancer. 2022 Oct;127(6):1051-1060. doi: 10.1038/s41416-022-01883-7. Epub 2022 Jun 23.

    PubMed 35739300

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Axitinib Oral Tablet in people with Renal Cell Carcinoma and Metastatic Renal Cell Carcinoma, run by Scottish Clinical Trials Research Unit at 7 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 2 inclusion and 18 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 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 30 Jun 2021). 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?

Number of Patients With a Change in Mayo Classification (time frame: Surgery and radiology assessment at week 9 in comparison to pre-axitinib assessment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03494816, which also lists 2 linked publications.

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 30 Jun 2021.

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