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

NCT01887522 | Terminated Phase 2

• 3 other identifiers: 2012-003005-10 Phase II2012/1883022
• Study Type: interventional
• Target: 144
• 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)

• Progression Free Survival (PFS)

  PFS computed as the time interval between the date of study entry and the date of tumor progression or death (whatever the cause of death). The progression will be defined either radiologically (\>25% increase in two-dimension measurements or appearance of new lesions compared to the baseline or to the best response after initiation of therapy) or clinically by new symptoms related to tumor progression (significant decrease of visual acuity, new or worsening neurological deficit). Hydrocephaly is not considered as progression per se.

  assessed up from randomization to tumor progression or death whatever the cause assessed up to 24 months

Study Arms (2)

VINILO

EXPERIMENTAL

VINILO-arm: Vinblastine and nilotinib given in combination at the RD defined in the Phase I part: * Vinblastine: administered in a 15-minute infusion, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle. * Nilotinib (Tasigna®): orally BID given continuously on Days 1- 28 Recommended doses of the drug combination will be reconsidered at an interim stage of the phase II trial after the analysis of the delayed toxicity encountered in the first 20 patients treated at the initial RD (adaptive design).

Drug: Vinblastine + Nilotinib

Control Vinblastine only

ACTIVE COMPARATOR

Control Vinblastine only arm: · Vinblastine 6 mg/m2 given in a 15-minute infusion, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle. Each 28-day cycle is repeated on Day 29/Day 1. In both treatment groups, dose reductions and/or administration delays will be performed in case of severe hematological and/or non hematological toxicities while on treatment. Vinblastine will be temporarily stopped in case of neutropenia \<1 x109/L or thrombopenia \<75 x 109/L. It could be re-started at a reduced dose after complete recovery. Patients benefiting from study treatment may continue up to 12 cycles as long as the toxicity-benefit ratio is adequate.

Drug: Vinblastine

Interventions

Vinblastine + Nilotinib DRUG

* Vinblastine: administered in a 15-minute infusion, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle. * Nilotinib (Tasigna®): orally BID given continuously on Days 1- 28

VINILO

Vinblastine DRUG

· Vinblastine 6 mg/m2 given in a 15-minute infusion, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle.

Control Vinblastine only

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, 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.
• 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 0 - 1 year: \<= 40 µmol/L
• years: \<= 65 µmol/L 15 - 20 years: \<= 110 µmol/L In case serum creatinine \>1.5 ULN according to age, creatinine clearance has to be \>70 mL/min/1.73 m2 or glomerular filtration rate measurement \>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
• Innovative Therapies For Children with Cancer Consortium: collaborator

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

MeSH Terms

Interventions

Vinblastine; nilotinib

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: June 27, 2013
• Study Start: July 6, 2016
• Primary Completion: April 20, 2019
• Study Completion: April 25, 2021
• Last Updated: May 31, 2022

Record last verified: 2022-05

Locations

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