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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02270034
Recruitment Status : Active, not recruiting
First Posted : October 21, 2014
Last Update Posted : January 8, 2021
Information provided by (Responsible Party):
Grupo Español de Investigación en Neurooncología

Tracking Information
First Submitted Date  ICMJE October 14, 2014
First Posted Date  ICMJE October 21, 2014
Last Update Posted Date January 8, 2021
Actual Study Start Date  ICMJE August 13, 2014
Actual Primary Completion Date October 26, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2018)
Treatment safety [ Time Frame: 7 months ]
Number of participants with adverse events as a measure of safety and tolerability
Original Primary Outcome Measures  ICMJE
 (submitted: October 17, 2014)
Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 7 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2018)
  • Recommended dose in phase II [ Time Frame: 7 months ]
    Based on pharmakinetic analysis by Cmax
  • Anti-tumor activity [ Time Frame: 7 months ]
  • Overall Survival [ Time Frame: Two years ]
    Time between start of treatment and death
Original Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2014)
  • Cmax [ Time Frame: 7 months ]
    Recommended dose in phase II
  • Anti-tumor activity [ Time Frame: 7 months ]
  • Overall Survival [ Time Frame: Two years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Study to Evaluate Safety and Activity of Crizotinib With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma
Official Title  ICMJE Phase Ib, Open-label, Multicenter, Dose-escalation Study Followed by an Extension Phase to Evaluate the Safety and Activity of the Combination of Crizotinib With Temozolomide and Radiotherapy in Patients With Newly Diagnosed Glioblastoma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme (Grade IV) of Cerebellum
Intervention  ICMJE Drug: Crizotinib
Crizotinib is added to Stupp method
Study Arms  ICMJE Experimental: Cohort crizotinib
Combination of crizotinib with temozolomide and radiotherapy following Stupp regime
Intervention: Drug: Crizotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 17, 2014)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Actual Primary Completion Date October 26, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Ability to understand and the willingness to sign a written informed consent document.
  2. Male or Female ≥18 years old and ≤ 70 years old
  3. Newly diagnosed glioblastoma (GB) confirmed by biopsy or resection 4-7 weeks before registration.
  4. 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).
  5. Patients must have sufficient time for recovery from prior surgery (at least 4 weeks).
  6. Karnofsky Performance Score (KPS) ≥ 60%.
  7. Adequate hematologic function: Hemoglobin ≥ 10 g/dL, Leukocytes > 3,000/mcL, absolute neutrophil count (UNL) ≥ 1,500 cells/ul, platelets ≥ 100,000 cells/ul.
  8. Adequate liver function: Bilirubin ≤ 2 X upper limit of normal (ULN); aspartate aminotrasferase (AST) (SGOT) ≤ 2.5 X ULN
  9. Creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2l for subjects with creatinine levels above institutional normal.
  10. 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.

Exclusion Criteria:

  1. Presence of extra-cranial metastatic disease.
  2. Any prior radiotherapy (RT) or chemotheraphy (QT) treatment.
  3. Patients must not have received prior Gliadel wafers.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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);
    • Heart rate <50/minute on pre-entry electrocardiogram;
    • Uncontrolled hypertension.
  9. Any patient with a history of significant cardiovascular disease, even if currently controlled, or who has signs or symptoms suggesting impaired left ventricular function in the judgment of the investigator must have a screening left ventricular ejection fraction (LVEF) evaluation by ECHO or angyography (MUGA). Patients with LVEF measurements below local institutional lower limit of normal or less than 50% will not be eligible.
  10. Individuals with a history of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. Patients will not be eligible if they have evidence of other malignancy requiring therapy other than surgery within the last 3 years.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02270034
Other Study ID Numbers  ICMJE GEINO 1402
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Grupo Español de Investigación en Neurooncología
Study Sponsor  ICMJE Grupo Español de Investigación en Neurooncología
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Chair: Juan Manuel Sepúlveda, MD Hospital 12 de Octubre
Study Chair: María Martínez, MD Hospital del Mar
PRS Account Grupo Español de Investigación en Neurooncología
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP