Axitinib in1st Line Treatment for Patients With Advanced or Metastatic Papillary Renal Cell Carcinoma

NCT02489695 | Completed Phase 2

• 2 other identifiers: AXIPAPET14-090
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 10

Brief Summary

Multicenter, single arm, phase II study using a A'Hern single-stage procedure in patients with locally advanced or metastatic papillary renal cell carcinoma (PRCC) in first-line treatment.

Conditions

Papillary Renal Cell Carcinoma

Keywords

locally advanced or metastatic

Outcome Measures

Primary Outcomes (1)

• The efficacy of axitinib in first-line treatment of PRCC.

  24-week progression-free rate

  24-week

Secondary Outcomes (6)

• The safety of axitinib in patients with PRCC (NCI CTCAE v4)

  Week 2, 4, 8, 16 then Month 4, 6, 8,10, 12, 14, 16,18

• The progression-free survival (RECIST 1.1) in each PRCC subtypes

  Week 2, 4, 8, 16 then Month 4, 6, 8,10, 12, 14, 16,18

• The overall survival

  43 month after first inclusion

• The best response

  Week 2, 4, 8, 16 then Month 4, 6, 8,10, 12, 14, 16,18

• the objective response rate

  Week 2, 4, 8, 16 then Month 4, 6, 8,10, 12, 14, 16,18

Study Arms (1)

axitinib + pembrolizumab

EXPERIMENTAL

axitinib 10mg twice a day

Drug: Axitinib

Interventions

Axitinib DRUG

axitinib 10mg twice a day

axitinib + pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• No prior systemic treatment for metastatic renal cancer (chemotherapy, immunotherapy, anti-angiogenic drugs, or treatment under evaluation).
• At least one measurable site of disease as defined by RECIST 1.1 criteria.
• ECOG performance status of 0, 1.
• No toxicity \> 1 according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0)
• In case of prior radiation therapy, discontinuation of irradiation for at least 4 weeks before first dose of study treatment. This period can be reduced to at least 1 week in case of radiotherapy in a limited field (\< 10% of the whole body) while no side effects grade ≥ 2 is expected and keeping at least one site for evaluation.
• Adequate bone marrow, liver and renal function, as defined below:
• Absolute neutrophil count ≥ 1.5 G/L, platelet count ≥ 100 G/L, and hemoglobin ≥ 9 g/dL),
• AST/ALT ≤ 3 x upper limit of normal (ULN) (or ≤ 5.0 x ULN if liver metastasis) and total bilirubin ≤ 1.5 x ULN (≤ 2.5 x ULN if liver metastases),
• Serum creatinine ≤ 2.0 x ULN or creatinine clearance ≥ 50 mL/min according to Cockroft formula or MDRD formula for patients older than 65 years,
• Absence of proteinuria confirmed by urinary dipstick test. If the dipstick test is ≥ 2+, proteinuria will be quantitated on a complete 24h urine sample (\< 1 g/L of protein/24h sample).
• Adequate contraceptive methods for fertile female subjects for the whole duration of the study and for 7 days after the last dose of study drug.
• Note: Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study.
• Covered by a medical insurance, in countries where applicable.
• Written informed consent before any study specific procedures or assessments.

You may not qualify if:

• Prior TKI treatment in adjuvant situation for renal cancer.
• Significant cardiovascular disease including:
• Disorder of left ventricular function with a LVEF \< 50%,
• Uncontrolled arterial hypertension under adapted medication: systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg or both despite appropriate therapy, or patients under 3 antihypertensive therapies at screening,
• History of serious ventricular arrhythmia (ie ventricular tachycardia or ventricular fibrillation),
• Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication),
• Coronary or peripheral artery bypass graft within 6 months of screening.
• Any active acute or chronic or uncontrolled infection/disorder that impair the ability to evaluate the patient or the ability for the patient to complete the study.
• Prior history of other malignancies other than PRCC (except for curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix) unless the subjects has been free of the disease for at least 3 years.
• Inability to swallow oral medications, or presence of active inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea.
• Patient included in another clinical trial, except for supportive care trials.
• Psychological, familial, sociological, or geographical conditions that would limit compliance with study protocol requirements.
• Pregnant or breastfeeding women (mandatory negative serum or urinary pregnancy test at study entry for all women of childbearing potential).

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (10)

ICO Paul Papin

Angers, 49933, France

Location

Chu Bordeaux

Bordeaux, 33075, France

Location

Centre Francois Baclesse

Caen, 14076, France

Location

Centre Geogres François Leclerc

Dijon, 21079, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

ICO - René Gauducheau

Saint-Herblain, 44805, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

ICL

Vandœuvre-lès-Nancy, 54519, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (2)

• Negrier S, Rioux-Leclercq N, Ferlay C, Gross-Goupil M, Gravis G, Geoffrois L, Chevreau C, Boyle H, Rolland F, Blanc E, Ravaud A, Dermeche S, Flechon A, Albiges L, Perol D, Escudier B; GETUG collaborative group. Axitinib in first-line for patients with metastatic papillary renal cell carcinoma: Results of the multicentre, open-label, single-arm, phase II AXIPAP trial. Eur J Cancer. 2020 Apr;129:107-116. doi: 10.1016/j.ejca.2020.02.001. Epub 2020 Mar 5.

  PMID: 32146304 BACKGROUND

• de Vries-Brilland M, Rioux-Leclercq N, Meylan M, Dauve J, Passot C, Spirina-Menand E, Flippot R, Fromont G, Gravis G, Geoffrois L, Chevreau C, Rolland F, Blanc E, Lefort F, Ravaud A, Gross-Goupil M, Escudier B, Negrier S, Albiges L. Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma. J Immunother Cancer. 2023 Nov;11(11):e006885. doi: 10.1136/jitc-2023-006885.

  PMID: 37935564 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Sylvie NEGRIER, PhD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

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: June 19, 2015
• First Posted: July 3, 2015
• Study Start: October 1, 2015
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: September 6, 2022

Record last verified: 2022-09

Locations

FR (10)