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

• ClinicalTrials.gov Identifier: NCT02597322
• Recruitment Status: Completed
• First Posted: November 5, 2015
• Last Update Posted: July 25, 2017
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Pfizer
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: June 8, 2015
• First Posted Date: November 5, 2015
• Last Update Posted Date: July 25, 2017
• Study Start Date: February 2012
• Actual Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 3, 2015): The number of patients actually experiencing a partial nephrectomy for a tumor ≤ 7cm [ Time Frame: At 6 months after beginning of the treatment ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 3, 2015)

• Response rate according to RECIST criteria [ Time Frame: 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. [ Time Frame: At 30 months after beginning of the treatment ]
• Renal function assessed by serum creatinin [ Time Frame: At baseline and at 30 months after beginning of the treatment ]
• Renal function assessed by calculated glomerular filtration rate (GFR) according to MDRD formula [ Time Frame: At baseline and at 30 months after beginning of the treatment ]
• Renal function assessed by renal scintigraphy [ Time Frame: At baseline and at 30 months after beginning of the treatment ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Axitinib for Downstaging Large Renal Tumors Not Primarily Suitable for Partial Nephrectomy (AXIPAN)
• Official Title: 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)

Brief Summary

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.

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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: cT2a N0NxM0 Renal Tumor

Intervention

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 Name: AG013736

Study Arms

Experimental: AXITINIB

Intervention: Drug: AXITINIB

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 24, 2017): 21
• Original Estimated Enrollment (submitted: November 3, 2015): 55
• Actual Study Completion Date: June 2017
• Actual Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02597322
• Other Study ID Numbers: P110209
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Assistance Publique - Hôpitaux de Paris
• Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Pfizer

Investigators

• Principal Investigator: Jean Jacques Patard, MD, PhD; Assistance Publique - Hôpitaux de Paris, Bicêtre Hospital

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: March 2017