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

NCT ID: NCT03494816

Last Updated: 2021-06-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-15
• Study Completion Date: 2020-06-10

Brief 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.

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.

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.

Conditions

Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma; Non-metastatic Renal Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Axitinib

Axitinib - oral tablet twice daily for 8 weeks prior to surgery. Starting dose 5mg.

Group Type: EXPERIMENTAL

Axitinib Oral Tablet

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Inlyta; AG-013736

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

1. For M1 patients: poor risk on Memorial Sloan Kettering Cancer Centre (MSKCC) score and deemed suitable for cytoreductive nephrectomy at time of enrolment.

2. 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.

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 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).

4. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine or pulmonary disease other than directly related to RCC.

5. 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.

6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 4.4, concomitant therapy).

7. Current use, or anticipated need for treatment with, drugs that are known CYP3A4 inducers or substrates for CYP1A2 (see section 4.4, 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. 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 ULN; Bilirubin ≥ 1.5 x ULN.

14. Serum creatinine ≥ 1.5 x ULN

15. Neutrophil count < 1.0 x 109/L; platelet count < 100 x 109/L; Hb ≤ 90g/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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Scottish Clinical Trials Research Unit

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Grant D Stewart

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge

Locations

Broomfield Hospital

Chelmsford, Essex, United Kingdom

Addenbrookes Hospital

Cambridge, , United Kingdom

Western General Hospital

Edinburgh, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Royal Free Hospital

London, , United Kingdom

St George's Hospital

London, , United Kingdom

Royal Marsden

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35739300 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000619-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN96273644

Identifier Type: OTHER

Identifier Source: secondary_id

NAXIVA

Identifier Type: -

Identifier Source: org_study_id