View Cancer Clinical Trials

Details

Title INTELLANCE 2: ABT-414 alone or ABT-414 plus temozolomide versus lomustine or temozolomide for recurrent glioblastoma: a randomized phase II study of the EORTC Brain Tumor Group

IRB ABBV1315

CC 15-791

Hospital Main Campus

Disease Brain, Glioblastoma

Drug ABT-414, Lomustine, Temozolomide

Description

• The objectives of the trial are to assess whether ABT-414 alone or in combination with TMZ improves overall survival (OS), PFS, tumor response, quality of life, NDFS and steroid use compared to standard treatment with lomustine single agent or TMZ re-challenge in patients with centrally confirmed recurrent EGFR-amplified glioblastoma.
• Additional exploratory objectives include analyses by stratum of EGFR pathway abnormalities (specifically EGFRvIII mutation), correlation of MGMT methylation status with clinical outcome (PFS/OS), and exploratory clinical and translational research program.
• The objectives will be achieved within a testing strategy, which aims to preserve the global type I error.
• The objectives will be realized according to the following hierarchical sequence: OS, PFS, response, OS in EGFRVIII mutated. Secondary objectives not included in the testing sequence will be realized for exploratory purpose.

Inclusion Criteria

Registration

• Histologically confirmed de novo (primary) glioblastoma before or at the time of first progression after RT concurrent/adjuvant TMZ chemotherapy.
  • In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy
• Age ≥ 18 years
• Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial.
• Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of EGFR amplification
• Written informed consent for central EGFR screening must be given according to ICH/GCP, and national/local regulations.

Randomization

• Histologically confirmed de novo (primary) glioblastoma with unequivocal first progression after RT concurrent/adjuvant TMZ chemotherapy either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy
• Presence of EGFR amplification confirmed by central assessment; patients with undetermined EGFR status are excluded
• WHO Performance status 0 - 2 (see Appendix C)
• No prior treatment with nitrosoureas
• No prior treatment with bevacizumab
• No previous exposure to EGFR targeted agents, including EGFRvIII targeting agents and participation to placebo controlled trials on EGFR taregeted agentsNo prior discontinuation of temozolomide chemotherapy for toxicity reasons
• No more than one line of chemotherapy for GBM (concurrent and adjuvant TMZ based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
• No prior RT with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
• No previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
• Absence of known hypersensitivity
  • to any part of the ABT-414 compound, TMZ, dacarbazine or lomustine formulations
  • to any IgG containing agent
• No history of Coeliac disease and wheat allergy
• Patient may have been operated for recurrence. If operated:
  • residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence
  • a post-surgery MRI must be available within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization
  • surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators. Criteria for full recovery will include absence of active post-operative infection, recovery from medical complications and capacity for fluid and food intake.
• For non-operated patients, recurrent disease must include at least one bi-dimensionally measurable contrast-enhancing lesion with clearly defined margins by MRI scan, with minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on an MRI scan done within 2 weeks prior to randomization
• Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan
• No current or recent (within 4 weeks before randomization) treatment with another investigational drug
• Patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to randomization
• No underlying or previous conditions that could interfere with treatment, including but not limited to:
  • no evidence of active infection requiring hospitalization or antibiotics, within 2 weeks prior to randomization
  • no active infectious keratitis
  • no other diseases interfering with follow up
• No planned vaccinations with live vaccines
• Adequate hematological function defined as: neutrophils ≥ 1.5 x 10⁹ cells/L and platelets ≥ 100 x 10⁹ cells/L and hemoglobin ≥ 6.2 mmol/L (9.9 g/dl)
• Normal liver function: bilirubin < 1.5x upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) < 2.5x ULN
• Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula (see Appendix E)
• Absence of pregnancy. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for 6 months beyond the end of treatment in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Females should not be breastfeeding.
  • Post menopause is defined as: amenorrhea ≥ 12 consecutive months without another cause or for women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
  • Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicide) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential.
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
  • Female patients within one year of entering the menopause must agree to use an effective nonhormonal method of contraception during the treatment period and for at least 6 months after the last study treatment.
• Males must agree to use an effective method of contraception during the treatment period and for at least 6 months after the last study treatment.
• Before patient randomization and study related procedures (that would not have been performed as part as standard care), written informed consent must be given according to ICH/GCP, and national/local regulations.
• Patients with a buffer range from the normal values of +/- 5 % for hematology and +/- 10% for biochemistry are acceptable. A maximum of +/- 2 days for timelines are acceptable (with the exception of the pregnancy test).

Exclusion Criteria

Exclusion Criteria Not Available