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

NCT03494816 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: NAXIVA2017-000619-17ISRCTN96273644
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Keywords

Neoadjuvant; Venous Tumour Thrombus; Axitinib; Mayo Classification; Nephrectomy; Thrombectomy

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (4)

• % Patients With Change in Surgical Management

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

• Change in Venous Tumour Thrombus (VTT) Height

  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.

• Number of Patients With RECIST Responses

  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.

• Surgical Complication Rates

  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.

Study Arms (1)

Axitinib

EXPERIMENTAL

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

Drug: Axitinib Oral Tablet

Interventions

Axitinib Oral Tablet 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.

Also known as: Inlyta, AG-013736

Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Scottish Clinical Trials Research Unit: lead
• Pfizer: collaborator

Study Sites (7)

Broomfield Hospital

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

St George's Hospital

London, SW17 0QT, United Kingdom

Location

Royal Marsden

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35739300 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Prof Grant Stewart
• Organization: University of Cambridge

gds35@cam.ac.uk

01223 256211

Study Officials

• Grant D Stewart

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2018
• First Posted: April 11, 2018
• Study Start: December 15, 2017
• Primary Completion: March 3, 2020
• Study Completion: June 10, 2020
• Last Updated: June 30, 2021
• Results First Posted: June 30, 2021

Record last verified: 2021-06

Locations

GB (7)