Study Of Vinblastine in Combination With Nilotinib in Children, Adolescents and Young Adults

NCT01884922 | Completed Phase 1

• 3 other identifiers: 2012-003005-10 Phase I2012/1883022
• Study Type: interventional
• Target: 35
• Locations: 8 countries
• Sites: 8

Brief Summary

Multicenter, open label, prospective study including successively a phase I trial and then a phase II trial Phase I : Open label, non-randomized, sequential dose escalation of both drugs, vinblastine and nilotinib.

Conditions

Refractory Low-grade Gliomas; Recurrent Low-grade Gliomas

Keywords

Children; adolescents; young adults

Outcome Measures

Primary Outcomes (1)

• Safety Assessment - Dose-Limiting Toxicity (DLT)

  Dose-Limiting Toxicity (DLT), assessed over the first 28-day cycle, defined as * Grade \> 3 neutropenia (\<1 x 109/L) for more than 7 days; * Grade \> 2 thrombopenia (\<75 x 109/L) or thrombocytopenia requiring transfusions for more than 7 days. * Grade 3 or grade 4 non-hematological toxicity, excluding grade 3 nausea, vomiting, fever, and hepatic toxicity that is rapidly reversible (i.e. returns to \< 2.5 x ULN within 2 weeks after study drug discontinuation), and symptoms that are related to tumor progression.

  Assessed over the first 28-day cycle

Study Arms (1)

Dose escalation

EXPERIMENTAL

Nilotinib (Tasigna®): 115 to 350 mg/m2 twice daily (BID) orally given continuously (115 mg/m2 once daily if de-escalation requested Vinblastine: 3 to 6 mg/m2 once weekly in a 15-minute infusion, on Days 1, 8, 15 and 22 of each cycle.

Drug: Nilotinib; Drug: Vinblastine

Interventions

Nilotinib DRUG

Tasigna®(nilotinib):: 50 mg, 150 mg and 200 mg capsules. Tasigna® capsules contain lactose monohydrate, crospovidone, poloxamer, colloidal silicon dioxide and magnesium. Orally; the capsules should be swallowed as a whole with water. No food should be consumed for 2 hours before the dose is taken and for at least one hour thereafter. For patients who are unable to swallow capsules, the content of each capsule may be dispersed in one teaspoon of apple sauce or compote or nonfat plain yogurt and should be taken immediately. Not more than one teaspoon of apple sauce / yogourt, and no food other than apple sauce or nonfat plain yogurt must be used.

Also known as: Tasigna®

Dose escalation

Vinblastine DRUG

Vinblastine: 3 to 6 mg/m2 once weekly in a 15-minute infusion, on Days 1, 8, 15 and 22 of each cycle. Each 28-day cycle is repeated on Day 29/Day 1. No intra-patient doseescalation is permitted. Dose allocation will be centrally defined, based on toxicity observed in patients previously evaluated. Every new patient will be treated at the best current recommended dose, i.e. the dose associated with an estimated level of toxicity that is judged acceptable (20% DLT). At least two patients fully observed with no DLT are requested at a given dose level before dose escalation.

Dose escalation

Eligibility Criteria

• Age: 6 Months - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed consent signed by the patient, or parents or legal representative and assent of the minor child.
• Age: 6 months to \< 21 years of age at time of study entry
• Histologically confirmed low-grade glioma in non-NF1 patients (no further biopsy is needed at study entry). For patients with NF1 and optic pathway glioma, no biopsy is required to confirm the radiological diagnosis of the low grade glioma.
• Relapse or refractory tumor after at least one first-line therapy, not taking into account surgery only.
• Evaluable Disease on morphologic MRI
• Karnofsky performance status score \>=70% for patients \>12 years of age, or Lansky score \>=70% for patients \<=12 years of age, including patients with motor paresis due to disease.
• Administration of stable dose of steroids for at least one week
• Life expectancy \>= 3 months.
• Adequate organ function:
• Adequate hematopoietic function: neutrophils ³1.0 x 109/L, platelets ³100 x 109/L; hemoglobin ³8 g/dL
• Adequate renal function: serum creatinine \< 1.5 x ULN for age In others cases where serum creatinine \>1.5 ULN according to age, Glomerular filtration rate or creatinine clearance has to be \>70 mL/min/1.73 m2 or \>70% of the expected value
• Adequate electrolytes levels: potassium, magnesium, phosphor, total calcium Lower Limit of Normal (LLN)
• Adequate hepatic function: total bilirubin \<=1.5 x ULN; AST and ALT \<=2.5 x ULN.
• Absence of peripheral neuropathy \>= grade 2 (Common Toxicity Criteria Adverse Event, NCI CTCAE v4.0)
• Adequate cardiac function:

You may not qualify if:

• Concomitant anti-tumor treatment
• Not recovered to \<Grade 2 from the acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy
• Known intolerance or hypersensitivity to Vinblastine
• Existence of another severe systemic disease
• Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines,
• Any concurrent illness which in the opinion of the investigator may interfere with the treatment and evaluation of the patient
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib.
• Simultaneous treatment with strong cytochromes P450 CYP3A4 inhibitors (e.g. antiepileptic drugs, see complete list in the Appendix 5).
• Simultaneous treatment with antiarrythmic drugs and other drugs known to prolong QT interval (cloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridil, cisapride and pimozide). A list of QT prolonging compounds can be found at http://www.azcert.org/medical-pros/druglists/drug-lists.cfm (Appendix 6)
• Impaired cardiac function including any one of the following:
• Clinically significant resting brachycardia (\<50 beats per minute).
• QTc \> 450 msec on baseline ECG. If QTc \>450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc.
• Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension).
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias (including congenital long QT syndrome or a known family history of congenital long QT syndrome)

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (8)

Medical University of Vienna

Vienna, A-1090, Austria

Location

Rigshospitalet

Copenhagen, DK - 2100, Denmark

Location

Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

University Hospital of Padua

Padua, 35128, Italy

Location

Erasmus MC/Sophia Children's Hospital

Rotterdam, 3015GJ, Netherlands

Location

Fundació Sant Joan de Déu

Barcelona, 08950, Spain

Location

Swiss Pediatric Oncology Group

Bern, 3008, Switzerland

Location

Cancer Research UK Clinical Trials Unit School of Cancer Sciences University of Birmingham

Edgbaston, Birmingham, B15 2TT, United Kingdom

Location

Related Publications (1)

• Vairy S, Le Teuff G, Bautista F, De Carli E, Bertozzi AI, Pagnier A, Fouyssac F, Nysom K, Aerts I, Leblond P, Millot F, Berger C, Canale S, Paci A, Poinsignon V, Chevance A, Ezzalfani M, Vidaud D, Di Giannatale A, Hladun-Alvaro R, Petit FM, Vassal G, Geoerger B, Le Deley MC, Grill J. Phase I study of vinblastine in combination with nilotinib in children, adolescents, and young adults with refractory or recurrent low-grade glioma. Neurooncol Adv. 2020 Jun 9;2(1):vdaa075. doi: 10.1093/noajnl/vdaa075. eCollection 2020 Jan-Dec.

  PMID: 32666050 DERIVED

MeSH Terms

Interventions

nilotinib; Vinblastine

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Jacques GRILL, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: June 24, 2013
• Study Start: May 29, 2013
• Primary Completion: September 2, 2015
• Study Completion: April 28, 2016
• Last Updated: May 27, 2022

Record last verified: 2022-05

Locations

FR (1); DK (1); IT (1); ES (1); CH (1); AU (1); GB (1); NL (1)