Avastin / Irinotecan in patients with recurrent or progressive malignant gliomaAn academic prospective single-arm phase II clinical trial for evaluation of advanced functional neuroimaging techniques and molecular markers in the course of anti-angiogenic therapies in malignant gliomas

Phase 1

• Conditions: First or second tumour recrurrence/progression of a histological confirmed supratentorial malignant glioma WHO Grade III-IV; MedDRA version: 12.0Level: LLTClassification code 10065443Term: Malignant glioma

• Registration Number: EUCTR2009-015036-15-AT
• Lead Sponsor: Medizinische Universität Innsbruck - Universitätsklinik für Neurologie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-17
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

[1]Patients present with a first or second tumor recurrence / progression of a histological confirmed supratentorial malignant glioma WHO Grade III-IV (Classification following WHO criteria).
Note: Patients may be entered based on neuropathology from the original diagnostic tumor specimen. For Translational Research Studies the original paraffin block - including sufficient tissue of the primary tumor - is required. Stereotactic biopsies or open biopsies of the primary malignant glioma without sufficient tumor tissue are not feasible and the patients must not be enrolled in this study.
[2]Patients with surgical resection of tumor recurrence / progression: Following standard therapy (first recurrent / progressed tumor) or standard therapy / second line chemotherapy excepting anti-angiogenic approaches (second recurrent /progressed tumor), patients must have evidence of further tumor progression measured by standard MRI sequences (MacDonald criteria). If possible, patients may have prior surgical resection of the tumor progression and will be eligible if the following conditions apply:
?Patients must have recovered from the effects of surgery
?To adequately asses the malignant glioma before surgery and the extent of residual disease postoperatively, two MRIs scans have to be performed:
?A first standard MRI scan has to be done within 1 week before surgery to document a progressed or recurrent malignant glioma.
?A second standard / functional MRI scan has to be done between 24 and 48 hours after surgery to document the postoperative malignant glioma (Baseline MRI scan).
Note: Patients must be on a steroid dosage that has been stable for at least 5 days before MRI. If the 48-hour scan is performed more than 14 days prior to study enrollment, the scan needs to be repeated (third MRI scan), however, the 24-48 hour MRI is the baseline scan.
?FET- / FLT-PET scans have to be done within 2 weeks after surgery to document the postoperative malignant glioma (Baseline PET scans).
Patients without surgical resection of the tumor recurrence / progression: Patients must have evidence of tumor progression measured by standard MRI sequences (MacDonald criteria).
?Additional functional MRI sequences have to be done within 1 week prior to study enrollment.
Note: Patients must be on a steroid dosage that has been stable for at least 5 days before MRI. If the 48-hour scan is performed more than 14 days prior to study enrollment, the scan needs to be repeated (third MRI scan), however, the 24-48 hour MRI is the baseline scan.
?FET- / FLT-PET scans have to be done within 2 weeks after surgery to document the postoperative malignant glioma (Baseline PET scans).
[3]Resolution of all acute toxic effects of prior therapy to grade = 1 (except alopecia, see Protocol Attachment A.5)
[4]Patients must have an ECOG performance status of 0-2 (refer to Protocol Attachment A.4)
[5]Patients must be = 18 years and = 80 years of age, with a life expectancy of greater than 8 weeks
[6]Patients must have adequate organ function as defined by the following criteria:
Bone Marrow Reserve-Platelets = 75.000/µL
-Absolute Neutrophil Count = 1500/µL
-Hemoglobin = 10.0 g/dL
Blood Coagulation-aPTT = 1.5 times upper limit of normal (ULN)
Hepatic Function -ASAT and ALAT = 2.5 times ULN
-ALP = 2.5 times ULN
-Total SERUM Bilirubin < 1.5 times ULN
Renal Function-SERUM Creatinine = 1.5 times ULN
Metabolism-SERUM Albumin = 3.0 g/dL
All tests must be performe

Exclusion Criteria

[9]The patient is active participant in another clinical trial, which investigates substances with anti-angiogenic effectiveness
[10]Exclusion of patients in the event of
?surgery of a recurrent / progressed malignant glioma within 2 weeks prior to study enrollment
?chemotherapy (Standardtherapy o Second Line Chemotherapy) within 2 weeks prior to study enrollment
?radiation therapy (Standardtherapy) within4 weeks to study enrollment
?evidence in baseline MRI of intratumoral or peritumoral hemorrhage deemed clinically significant by the treating physician (area of hemorrhage > 25% of tumor area)
[11]Significant Co-Morbidities within 12 months prior to study enrollment
?myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure
?cerebrovascular accident including transient ischemic attack
[12]Significant Co-Morbidities at Baseline Evaluation
?Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
?pulmonary embolus within4 weeks to study enrollment
?A known HIV (human immunodeficiency virus) or Hepatitis B/C infection or severe acute infection
[13]Anticoagulation: Current treatment with therapeutic doses of Marcoumar / Sintrom excluding thrombosis prophylaxis with low dose Heparin.
[14]Pregnancy, Breastfeeding and Non-Contraception
?Female patients who are pregnant or nursing
?Patients who are sexually active and unwilling or unable to use a medically acceptable method of contraception during the trial.
Note: Female and male patients with reproductive potential have to use an approved contraceptive method (e.g., hormonal contraception, intrauterine device, condom with spermicide, etc.) during and for 3 months after discontinuation of study treatment. Female Patients with child-bearing age must have a negative serum pregnancy test = 3 days prior to study enrollment. During study treatment pregnancy has to be excluded (serum pregnancy tests every 2 weeks until tumor progression).
[15]Evidence of increased intracranial pressure
?midline shift > 5 mm
?headache, distinct nausea and vomiting
[16]Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would impart excess risk associated with study participation or study drug administration, or which would make the patient inappropriate for entry into this study. The decision to enroll the patient in this study is in the judgment of the investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine<br>- the objective radiological response (RR), objective radiological response rate (ORR) and objective response duration (ORD) using MRI and PET neuroimaging<br>- the predictive / prognostic value of the MRI / PET neuroimaging data for Avastin / Irinotecan chemotherapy due to comparing with the clinical trial parameters (time to tumor progression TTP, progression free survival rate at 6 months PFS6, overall survival OS and overall survival rate at 12 months OS12)<br>- the safety and tolerability of Avastin / Irinotecan chemotherapy in malignant glioma patients<br><br><br><br>;Secondary Objective: To compare MRI / PET neuroimaging parameters<br>- with each other using image fusion methods<br>- with Quality of Life (QOL)<br>- with Molecular Tissue and Serum / Plasma Biomarkers;Primary end point(s): - Objective response criteria (RR, ORR, ORD) asses by Standard MRI and FET-/FLT-PET during Avastin/Irinotecan chemotherapy