Study to Evaluate Safety and Activity of Crizotinib With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma

NCT02270034 | Completed Phase 1

• 1 other identifier: GEINO 1402
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

Brief Summary

This multicenter, open-label, phase Ib trial aims to assess the safety and activity and safety of crizotinib (in combination with radiotherapy and temozolomide) in adult patients with newly diagnosed glioblastoma.

Conditions

Glioblastoma Multiforme (Grade IV) of Cerebellum

Outcome Measures

Primary Outcomes (1)

• Treatment safety

  Number of participants with adverse events as a measure of safety and tolerability

  7 months

Secondary Outcomes (3)

• Recommended dose in phase II

  7 months

• Anti-tumor activity

  7 months

• Overall Survival

  Two years

Study Arms (1)

Cohort crizotinib

EXPERIMENTAL

Combination of crizotinib with temozolomide and radiotherapy following Stupp regime

Drug: Crizotinib

Interventions

Crizotinib DRUG

Crizotinib is added to Stupp method

Cohort crizotinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document.
• Male or Female ≥18 years old and ≤ 70 years old
• Newly diagnosed glioblastoma (GB) confirmed by biopsy or resection 4-7 weeks before registration.
• Patients must have at least 15 unstained slides or 1 tissue block (frozen or paraffin embedded) available from a prior biopsy or surgery (archival tumor material).
• Patients must have sufficient time for recovery from prior surgery (at least 4 weeks).
• Karnofsky Performance Score (KPS) ≥ 60%.
• Adequate hematologic function: Hemoglobin ≥ 10 g/dL, Leukocytes \> 3,000/mcL, absolute neutrophil count (UNL) ≥ 1,500 cells/ul, platelets ≥ 100,000 cells/ul.
• Adequate liver function: Bilirubin ≤ 2 X upper limit of normal (ULN); aspartate aminotrasferase (AST) (SGOT) ≤ 2.5 X ULN
• Creatinine within normal institutional limits or creatinine clearance \> 60 mL/min/1.73 m2l for subjects with creatinine levels above institutional normal.
• The effects of crizotinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or harrier method of birth control; abstinence; surgical sterilization) prior to study entry and for the duration of study participation and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 2 weeks prior to starting treatment.

You may not qualify if:

• Presence of extra-cranial metastatic disease.
• Any prior radiotherapy (RT) or chemotheraphy (QT) treatment.
• Patients must not have received prior Gliadel wafers.
• The use of enzyme-inducing antiepileptic drugs will not be allowed. Those patients taking enzyme-inducing antiepileptic drugs required a 7-day washout period before registration.
• Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
• Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication in tablet form.
• Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol.
• Uncontrolled or significant cardiovascular disease, including:
• A myocardial infarction within 12 months;
• Uncontrolled angina within 6 months;
• Congestive heart failure within 6 months;
• Diagnosed or suspected congenital long QT syndrome;
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
• Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (\>470 msec);
• Any history of second or third degree heart block (may be eligible if currently have a pacemaker);

Sponsors & Collaborators

• Grupo Español de Investigación en Neurooncología: lead
• Pfizer: collaborator

Study Sites (4)

Institut Català D'Oncologia L'Hospitalet (Ico)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Del Mar

Barcelona, 08003, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Crizotinib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Juan Manuel Sepúlveda, MD

  Hospital 12 de Octubre

  STUDY CHAIR

• María Martínez, MD

  Hospital del Mar

  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: October 14, 2014
• First Posted: October 21, 2014
• Study Start: August 13, 2014
• Primary Completion: October 26, 2020
• Study Completion: October 26, 2020
• Last Updated: March 10, 2022

Record last verified: 2022-02

Locations

ES (4)