Trial investigating a personalized treatment, based on age and tumor characteristics , of newly diagnosed medullablastoma in patients that are postpubertal and/or adult consisting of lowering RT,chemotherapy doses and adding an investigative drug.

Korábbi kezelés

• Step 2: Enrollment/randomization: Prior treatment for medulloblastoma
• Step 2: Enrollment/randomization: Concurrent severe or uncontrolled medical disease (e.g., active systemic infection, diabetes, psychiatric disorder) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study.
• Step 2: Enrollment/randomization: Prior or second invasive malignancy, except non-melanoma skin cancer, completely resected cervical carcinoma in situ, low risk prostate cancer (cT1-2a N0 and Gleason score ≤ 6 and PSA < 10 ng/mL), either totally resected or irradiated with curative intent (with PSA of less than or equal to 0.1 ng/mL) or under active surveillance as per ESMO guidelines. Other cancers for which the subject has completed potentially curative treatment more than 5 years prior to diagnosis of medulloblastoma study entry are allowed.
• Step 2: Enrollment/randomization: Inability to start radiotherapy within 56 days after surgery.
• Step 2: Enrollment/randomization: Any medical contraindication to radiotherapy or chemotherapy
• Step 2: Enrollment/randomization: Current use of BCRP substrates such as mitoxantrone, methotrexate, topotecan, imatinib or irinotecan or if patient is within 5 times the half-life of these medications

Más betegség

• Step 2: Enrollment/randomization: Known history or current evidence of active Hepatitis B (e.g., positive HBV surface antigen) or C (e.g., HCV RNA [qualitative] is detected)
• Step 2: Enrollment/randomization: Known or current evidence of Human Immunodeficiency Virus (HIV) infection (positive HIV-1/2 antibodies)
• Step 2: Enrollment/randomization: Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Step 2: Enrollment/randomization: Significant sensorineural hearing deficit as defined by pure tone audiometry with bone conduction or air conduction and normal tympanogram showing impairment ≥ 20 dB at 1-3 kHz
• Step 2: Enrollment/randomization: Hypersensitivity to contrast medium for MRI.
• Step 2: Enrollment/randomization: Hypersensitivity towards the active substance of any of study drugs or their excipients

Egyéb

• Step 2: Enrollment/randomization: Unavailability of central review pathology results
• Step 2: Enrollment/randomization: Post-pubertal patients with known negative prognostic markers (MYC/MYCN amplification and/or TP53 germline alteration in the SHH subgroup)

• Step 1: Registration: Before patient registration/randomization/enrollment, written informed consent must be given according to ICH/GCP, and national/local regulations. For patients under the age of legal consent, consent has to be obtained from the parent(s) or legal representative according to ICH/GCP, and national/local regulations.
• Step 2: Enrollment/randomization: Clinical status within 2 weeks of randomization/enrollment: Karnofsky 50-100
• Step 2: Enrollment/randomization: NANO-score 0 to 9 (allowing full-blown cerebellar symptoms)
• Step 2: Enrollment/randomization: Clinically standard-risk (centrally assessed MRI review on pre- and postoperative MRI) defined as: • Adult patients: total or subtotal surgical resection defined as at least 80% reduction of the contrast enhancing tumour and/or less than or equal to 1.5 cm2 (measured in axial plane) of residual tumour on early post-operative MRI, without and with contrast. • Post-pubertal patients: total or near total surgical resection with less than or equal to 1.5 cm2 (measured in axial plane) of residual tumour on early post-operative MRI, without and with contrast • No CNS metastasis on MRI (cranial and spinal) • Chang stage
• Step 2: Enrollment/randomization: No evidence of extra-CNS metastasis
• Step 2: Enrollment/randomization: Full recovery from surgery or any post-surgical complication (e.g., bleeding, infections etc.)
• Step 2: Enrollment/randomization: Baseline MRI as the following: • Brain MRI: pre- and post- surgery (within 72h) MRI is mandatory. • Spine MRI: preferably pre-operative. If not available, post-operative is acceptable.
• Step 2: Enrollment/randomization: Normal liver, renal and haematological function within 2 weeks of randomization/enrollment. • WBC ≥ 3×10^9/L • ANC ≥ 1.5×10^9/L • Platelet count of ≥ 100×10^9/L independent of transfusion • Hemoglobin ≥ 10 g/dl • Total Bilirubin ≤ 1.5 × ULN • ALT (SGPT), AST (SGOT), alkaline phosphatase (ALP) ≤ 2.5 × ULN • Serum creatinine < 1.5 × ULN or creatinine clearance (CrCl) >60 mL/min (the estimated GFR should be in mL/min/1.73m² unit, using the MDRD formula)
• Step 2: Enrollment/randomization: According to CTFG recommendations related to contraception and pregnancy testing during clinical trials, a negative serum or urine pregnancy test within 7 days before randomization/enrollment for women of childbearing / reproductive potential (WOCBP).
• Step 2: Enrollment/randomization: WOCBP must use two methods of adequate birth control, including a highly effective method and a barrier method. Birth control during the study treatment period and for at least 20 months after the last study treatment is mandatory for patients who receive sonidegib. For all other patients, this period is 12 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e., less than 1% per year) when used consistently and correctly.
• Step 2: Enrollment/randomization: Male patients even those who have had a vasectomy must always use a condom during treatment and for 12 months after last treatment. Men should not donate semen during treatment and for 12 months after ending treatment (donation of semen for the semen analyses in the 1 b fertility project is allowed)
• Step 1: Registration: FFPE tumour tissue from surgical resection and whole blood for central pathology review must be available.
• Step 2: Enrollment/randomization: Female subjects who are breast feeding must discontinue nursing prior to the first dose of study treatment and until 20 months after the last study treatment.
• Step 2: Enrollment/randomization: Newly diagnosed, histologically proven, genetically classified, centrally confirmed medulloblastoma
• Step 2: Enrollment/randomization: Molecular subtype: medulloblastoma, SHH-activated, M0-1; medulloblastoma, WNT-activated, M0-1; medulloblastoma, Group 3 & Group 4, M0-1
• Step 2: Enrollment/randomization: Histologic subtype: medulloblastoma, classic (CMB); medulloblastoma, desmoplastic/nodular (DNMB); medulloblastoma, with extensive nodularity (MBEN); medulloblastoma, large cell/anaplastic (LCA)
• Step 2: Enrollment/randomization: Post-pubertal patients (<18y of age), or adults (18 y of age and above) in SHH-activated medulloblastoma.
• Step 2: Enrollment/randomization: Adults (≥ 18 years) in the WNT-activated, Group 3 & Group 4 medulloblastoma.
• Step 2: Enrollment/randomization: Patients (<18 years) must have completed puberty.
• Step 2: Enrollment/randomization: Patients (<18 years) must have a radiologically confirmed bone age of minimum 15 years for females and 17 years for males.