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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 March 2022
• Main ID: NCT02270034
• Date of registration: 14/10/2014
• Prospective Registration: No
• Primary sponsor: Grupo Español de Investigación en Neurooncología
• Public title: Study to Evaluate Safety and Activity of Crizotinib With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma
• Scientific title: 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
• Date of first enrolment: August 13, 2014
• Target sample size: 38
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02270034
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Spain

Contacts

• Name: Juan Manuel Sepúlveda, MD
• Affiliation: Hospital 12 de Octubre

• Name: María Martínez, MD
• Affiliation: Hospital del Mar

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Glioblastoma Multiforme (Grade IV) of Cerebellum

Intervention(s)

Drug: Crizotinib

Primary Outcome(s)

Treatment safety [Time Frame: 7 months]

Secondary Outcome(s)

Overall Survival [Time Frame: Two years]

Recommended dose in phase II [Time Frame: 7 months]

Anti-tumor activity [Time Frame: 7 months]

Secondary ID(s)

GEINO 1402

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Pfizer