A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy

NCT01693822 | Completed Phase 2 Results DMC

• 1 other identifier: ICR-CTSU/2011/10033
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 11

Brief Summary

A-PREDICT is a study of axitinib in patients with metastatic renal cell carcinoma unsuitable for nephrectomy (as judged by the treating clinician) to evaluate efficacy, safety, toxicity and changes in biomarkers during therapy. Axitinib will given twice daily by mouth according to tolerability of treatment, for as long as patients are deriving clinical benefit. Blood and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. The primary clinical objective of this study is to define the activity of axitinib given to patients with metastatic renal cell carcinoma unsuitable for nephrectomy.

Conditions

Clear-cell Metastatic Renal Cell Carcinoma

Keywords

metastatic renal cell carcinoma; predominant clear cell histology; Unsuitable for nephrectomy; unsuitable for 'watch and wait' policy

Outcome Measures

Primary Outcomes (1)

• Freedom From Progression at 6 Months

  The proportion of study participants alive and progression free at 6 months (day 1 week 25 visit). Progression will be measured from the date of study entry (registration date) until the first date of either death or confirmed progressive disease according to RECIST v1.1 (https://recist.eortc.org/recist-1-1-2/). Patients alive and free from progression will be censored at the date of last follow-up. The proportion of patients progression free at 6 months will be reported with 95% confidence interval. In addition, progression free survival will be presented using the Kaplan Meier product limit method with median progression free survival reported. A blinded central review of CT scans will be conducted for verification purposes.

  6 months

Secondary Outcomes (5)

• Best Overall Response

  From registration, during treatment and up to 30 days after treatment discontinuation. Patients remain on treatment until disease progression assessed up to 106 months.

• Progression Free Survival

  From the date of registration until first date of either death or confirmed progressive disease from any cause, whichever came first, assessed up to 106 months.

• Overall Survival

  From the date of registration until the date of death due to any cause, up to 106 months.

• Safety and Toxicity of Axitinib (by NCI CTC Grading Version 4)

  Treatment duration (at least 4 weekly, and again at disease progression), up to 106 months.

• Number of Patients Who Become Suitable for Nephrectomy as a Consequence of Therapy With Axitinib

  Study duration (assessed by clinician over treatment duration), up to 106 months.

Study Arms (1)

Axitinib

EXPERIMENTAL

Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg.

Drug: Axitinib

Interventions

Axitinib DRUG

Axitinib treatment 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. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. 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: 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:

• Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology
• Unsuitable for nephrectomy
• Unsuitable for 'watch and wait' policy
• No prior systemic therapy for renal cell carcinoma
• Measurable metastatic disease using RECIST v1.1
• Life expectancy 12 weeks or greater
• ECOG performance status 0 or 1
• Adequate organ function as defined by serum aspartate transaminase (AST) or serum alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due to liver metastases; total serum bilirubin ≤1.5 x ULN
• Adequate haematological function as defined by absolute neutrophil count (ANC) ≥1500/μL, platelets ≥75,000/μL, haemoglobin ≥9.0 g/dL and prothrombin time (PT) ≤1.5 x ULN
• Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min;
• Urinary protein \<2+ by urine dipstick.
• No evidence of pre-existing uncontrolled hypertension
• Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
• Willingness and ability to comply with study procedures, including tumour biopsies.
• Written informed consent

You may not qualify if:

• The presence of intracranial disease, unless stable \>6 months. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months post-surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days.
• The presence of active second malignancy.
• 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.
• Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
• Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC.
• Gastrointestinal abnormalities including:
• inability to take oral medication;
• requirement for intravenous alimentation;
• prior surgical procedures affecting absorption including total gastric resection;
• treatment for active peptic ulcer disease in the past 6 months;
• 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;
• malabsorption syndromes.
• Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy).
• Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, 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.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Pfizer: collaborator
• Royal Marsden NHS Foundation Trust: collaborator

Study Sites (11)

Royal Surrey County Hospital

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Royal Marsden Hospital - Sutton

London, Sutton, SM2 5PT, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Guy's Hospital

London, Se1 9RT, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Related Links

• ICR-CTSU trial page

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; 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: Professor Judith Bliss (Director of ICR-CTSU)
• Organization: Institute of Cancer Research, Clinical Trials and Statistics Unit (ICR-CTSU)

apredict-icrctsu@icr.ac.uk

+44 0208 722 4297

Study Officials

• James Larkin

  Royal Marsden Hospital London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: August 6, 2012
• First Posted: September 26, 2012
• Study Start: October 1, 2012
• Primary Completion: March 1, 2017
• Study Completion: February 28, 2022
• Last Updated: November 21, 2024
• Results First Posted: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will become available to researchers following the formal review and approval of a data access request in accordance with the ICR-CTSU data and sample access policy.
• Access Criteria: Completion and approval of a data access request form as stated above.

Locations

GB (11)