Study of Axitinib for Downstaging Large Renal Tumors Not Primarily Suitable for Partial Nephrectomy (AXIPAN) (AXIPAN)

An Open-label, Non-randomized, Multicenter, Two Stage Designed Phase II Study of Axitinib for Downstaging Large Renal Tumors Not Primarily Suitable for Partial Nephrectomy (AXIPAN)

Axitinib (AXITINIB) is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 which has achieved objective response rate of 44.2% in phase II study in cytokine-refractory metastatic renal-cell cancer patients.

Pre-surgical treatment with Axitinib could allow a substantial proportion of patients with large organ confined tumors to benefit from NSS.

The Objective is to determine the efficacy of Axitinib administered prior to surgery in patients with large organ confined tumors not primarily suitable for NSS (cT2aNoNxM0) for shifting from a radical nephrectomy indication to a nephron sparing procedure.

Study Overview

• Status: Completed
• Conditions: cT2a N0NxM0 Renal Tumor
• Intervention / Treatment: Drug: AXITINIB

Detailed Description

Radical nephrectomy (RN) is the current standard of care for large organ confined renal tumors.

Experience and surgical technical improvements have allowed the feasibility of Nephron Sparing Surgery (NSS) in tumors larger than 4 cm and up to 7cm. Very limited data exist regarding the feasibility and safety of NSS in tumors larger than 7cm.

It has been demonstrated that NSS compared to RN offers similar oncological outcome while better preserving renal function and thus improving overall survival.

The purpose of this study is to test the possibility of offering patients with large organ confined renal tumors, candidates for radical nephrectomy according to current guidelines the benefit of partial nephrectomy thanks to axitinib neo-adjuvant treatment.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Le Kremlin Bicêtre, France, 94275
    • Bicêtre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must sign IRB/EC-approved informed consent.
• Age ≥ 18
• Histologically proven clear cell RCC (obtained by CT or US guided biopsy)
• cT2a N0NxM0 Renal tumor according to 2009 TNM classification (tumor Ø> 7cm; ≤ 10 cm)
• No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart.
• Normal renal function (MDRD creatinin clearance ≥ 60 ml/min)
• Patients must have adequate organ function defined as: Platelets ≥ 150 x 109/L, hemoglobin > 9 g/dl, absolute neutrophil count (ANC) >1.5 x 109/L; Bilirubin < 2 mg/dL, aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal; Total cholesterol ≤ 9.1 mmol/l and triglyceride level ≤ 4.5 mmol/l
• Urinary protein <2+ by urine dipstick.
• Patients with reproductive potential must use medically acceptable contraceptive method.
• Beneficiary of a social coverage (except AME)

Exclusion Criteria:

• Patients with < 50 % clear cell histology
• Evidence of locally advanced disease: cT stage≥T2b, N Stage≥1 or metastatic disease (M1)
• Patients must not be pregnant or lactating.
• Patients must not have uncompensated coronary artery disease or an history of myocardial infarction or severe or unstable angina within the past six months or severe diabetes mellitus with severe arterial peripheral disease or deep venous or arterial thrombosis or embolism with the past 3 months. Patients must not need curative anticoagulants.
• Patients must not have any medical/systemic or psychiatric disorder incompatible with the study.
• Patients must not have a history of significant gastric or small bowel resection, malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may compromise the absorption of Axitinib or an unavailability of the oral route.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AXITINIB	Drug: AXITINIB; Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, 3 It will be supplied as 1 mg and 5 mg film coated tablets for oral administration in light protecting bottles of 60 tablets.; Other Names: AG013736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of patients actually experiencing a partial nephrectomy for a tumor ≤ 7cm	At 6 months after beginning of the treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Response rate according to RECIST criteria	At 30 months after beginning of the treatment
Number of participants with treatment-related serious adverse events and their grades according to CTCAE V4.0.	At 30 months after beginning of the treatment
Renal function assessed by serum creatinin	At baseline and at 30 months after beginning of the treatment
Renal function assessed by calculated glomerular filtration rate (GFR) according to MDRD formula	At baseline and at 30 months after beginning of the treatment
Renal function assessed by renal scintigraphy	At baseline and at 30 months after beginning of the treatment

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Pfizer
• Investigators: Principal Investigator: Jean Jacques Patard, MD, PhD, Assistance Publique - Hôpitaux de Paris, Bicêtre Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: June 8, 2015
• First Submitted That Met QC Criteria: November 3, 2015
• First Posted (Estimated): November 5, 2015

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 4, 2025
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Axitinib; radical nephrectomy; nephron sparing surgery; T2a Renal tumor; organ confined tumors; nephron sparing procedure
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Kidney Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: P110209