A study of vismodegib (GDC-0449) in combination with temozolomide in adult patients with recurrent, progressive, or refractory medulloblastoma
- Conditions
- Recurrent, progressive or refractory medulloblastoma with activation of the SHH pathwayMedDRA version: 14.1 Level: PT Classification code 10066594 Term: Medulloblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-003372-37-FR
- Lead Sponsor
- CENTRE LEON BERARD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 38
I1. Age = 18 years.
I2. Patients must have histologically confirmed medulloblastoma (including posterior fossa primitive neuroectodermal tumor) for which no known curative therapy exists.
I3. Patients must have recurrent or refractory disease
I4. Patients must have evidence of measurable disease or lesion in pre-inclusion MRI. Patients with measurable spinal disease are eligible. NB: Patients with complete resection for recurrence are not eligible.
I5. The activation of the SHH pathway must be validated by IHC before initiation of treatment.
I6. ECOG performance status 0, 1 or 2 (Appendix 4).
I7. Life expectancy = 12 weeks (as determined by treating physician).
I8. Patients must have normal organ and marrow function as defined below:
?Neutrophils = 1. 5 G/L
?Platelets = 100 G /L (transfusion-independent)
?Hemoglobin = 10g/dL (RBC transfusions allowed)
?Creatinine clearance = 50 mL/min (calculated by Cockcroft-Gault formula or MDRD formula for patients older than 65 years ) or serum within normal limits or less than 1.5 x upper limit of normal (ULN)
?Total bilirubin = 1.5 times ULN
?ALT and AST = 2.5 times ULN
?Serum albumin = 25 g/L.
I9. Recovered from prior treatment-related toxicity (persistent treatment related toxicity I10. Prior therapy:
?No prior hedgehog antagonist vismodegib or other antagonists of the hedgehog pathway, and no prior temozolomide treatment.
?More than 4 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas, 6 months after high dose therapy) or immunotherapy
?At least 3 months since prior craniospinal irradiation (= 23 Gy)
?At least 8 weeks since prior local irradiation to primary tumor
?At least 2 weeks since prior focal irradiation for symptomatic metastatic sites.
?At least 1 week since prior colony-stimulating factors (e.g., G-CSF, GM-CSF, or erythropoietin)
I11. Women of childbearing potential* are required to have a negative serum pregnancy test within 72 hours prior to study treatment initiation (i.e. Cycle 1 Day 1).
o*: Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential:
o=50 years old and naturally amenorrheic for = 1 year
oPermanent premature ovarian failure confirmed by a specialist gynaecologist
oPrevious bilateral salpingo-oophrectomy
oXY genotype, Turner’s syndrome, or uterine agenesis
Female patient who do not meet at least of the above criteria are defined as women of childbearing potential.
I12. An embryo-fetal development study in rats has confirmed the teratogenic potential of vismodegib. Therefore, women of child-bearing potential and men must use two forms of effective contraception (including one barrier method- refer to Appendix 5 for acceptable method of contraception) at least 4 weeks prior to study entry, during the study participation and for at least 7 months post-treatment. Prior to dispensing vismodegib, the investigator m
- Tumor Tissue samples (either from the initial diagnosis and/or relapse) not available for biological studies.
- Pregnant or breastfeeding women.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vismodegib.
- Any contraindications to Temozolomide treatment as per Temodal SPC (i.e. hypersensitivity to the active substance or to any of the excipients, Hypersensitivity to dacarbazine (DTIC)).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method