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

NCT ID: NCT01693822

Last Updated: 2024-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2022-02-28

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.

Detailed Description

A-PREDICT is a single arm, single agent, open label, multicentre, phase II study of axitinib in patients with metastatic renal cell carcinoma of predominant clear cell histology and unsuitable for debulking nephrectomy (as judged by the treating clinician). Patients who have provided consent and have satisfied the eligibility criteria will be registered into the trial.

The starting dose of axitinib will be 5 mg twice daily by mouth, escalating to a maximum of 10mg twice daily by mouth according to tolerability of treatment, for as long as patients are deriving clinical benefit. Treatment will be paused for one week prior to percutaneous biopsy of the primary on day 1 week 9. Disease progression will be evaluated according to RECIST v1.1 criteria 8 weeks after commencing treatment, at 8 weekly intervals to 6 months and 3 monthly thereafter. Blood and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. Nephrectomy will be carried out on any patient who becomes suitable in the opinion of the treating clinician during the course of the trial. Where possible, tissue samples will be taken from resected specimens. Response to axitinib in marker lesions will be correlated with changes in biomarkers.

Conditions

Clear-cell 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 until disease progression. Starting dose 5mg.

Group Type: EXPERIMENTAL

Axitinib

Intervention Type: 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.

Interventions

Axitinib

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.

Intervention Type: DRUG

Other Intervention Names

AG-013736

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology

2. Unsuitable for nephrectomy

3. Unsuitable for 'watch and wait' policy

4. No prior systemic therapy for renal cell carcinoma

5. Measurable metastatic disease using RECIST v1.1

6. Life expectancy 12 weeks or greater

7. ECOG performance status 0 or 1

8. 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

9. 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

10. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min;

11. Urinary protein <2+ by urine dipstick.

12. No evidence of pre-existing uncontrolled hypertension

13. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.

14. Willingness and ability to comply with study procedures, including tumour biopsies.

15. Written informed consent

Exclusion Criteria

1. 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.

2. The presence of active second malignancy.

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.

4. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.

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

6. Gastrointestinal abnormalities including:

1. inability to take oral medication;

2. requirement for intravenous alimentation;

3. prior surgical procedures affecting absorption including total gastric resection;

4. treatment for active peptic ulcer disease in the past 6 months;

5. 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;

6. malabsorption syndromes.

7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy).

8. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, concomitant therapy).

9. 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.

10. Active seizure disorder, spinal cord compression, or carcinomatous meningitis.

11. 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.

12. Deep vein thrombosis or pulmonary embolism within 6 months prior to study entry.

13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

14. Known galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

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

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Larkin

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden Hospital London

Locations

Royal Surrey County Hospital

Guildford, Surrey, United Kingdom

Royal Marsden Hospital - Sutton

London, Sutton, United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

Western General Hospital

Edinburgh, , United Kingdom

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Guy's Hospital

London, , United Kingdom

Royal Marsden Hospital

London, , United Kingdom

Christie Hospital

Manchester, , United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.icr.ac.uk/our-research/centres-and-collaborations/centres-at-the-icr/clinical-trials-and-statistics-unit/our-research/clinical-trials/a-predict

ICR-CTSU trial page

Other Identifiers

ICR-CTSU/2011/10033

Identifier Type: -

Identifier Source: org_study_id