Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults

Study Overview
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Brief Summary
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The purpose of this study is to determine whether a combination of a radiochemotherapy (vincristin) and a following maintenance chemotherapy (vincristin, cisplatin and CCNU) in adult patients with medulloblastoma is tolerable.

Detailed Description
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As medulloblastoma in adult patients are very rare (1.1% of all brain tumors), adults are often treated in the scope of expanded access treatments or within pediatric studies; although, it is not known whether medulloblastomas act in the same way in adulthood and in childhood. This is the first study to investigate the significance of a combination of a radiochemotherapy (vincristin) and a following maintenance chemotherapy (vincristin, cisplatin and CCNU) in adult patients with medulloblastoma with the purpose to have a starting point for the development of chemotherapeutical protocols in adults.

Official Title
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Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-07)

Conditions
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Medulloblastoma

Intervention / Treatment
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* Drug: maintenance chemotherapy (vincristin, cisplatin and CCNU)
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 years medulloblastoma (+/- postoperative residual tumor, M0) or medulloblastoma (+/- postoperative residual tumor, M1-M3) respectively primary diagnosis of the tumor no previous chemo- or radiation therapy Karnofsky-Index ≥ 70% WBC ≥ 3000/μl; thrombocytes ≥ 100 000/μl; Hb ≥ 10 g/dl creatinine =< 1,5 ULN; Bilirubin =< 1,5 ULN; GPT, GOT, AP =< 2,5 ULN HIV and hepatitis B/C negative no factors / any medical condition affecting patient's compliance patient needs to fulfil protocol's requirements patient is willing to use highly effective methods of contraception during dosing and for 6 months after the last dose; women of child-bearing potential must have a negative hCG laboratory test at baseline; pregnancy tests must be repeated every 4 weeks patient's written consent Exclusion Criteria: age < 18 years histologically not confirmed Medulloblastoma by chemo- or radiotherapy treated recidive tumor other cancer (with exception of surgically cured carcinoma in situ of the cervix and non-melanocytic skin tumors) hypersensitivity or contraindication against one of the used drugs current or planned participation to another clinical trial during this study Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrolment or could interfere with the patient participating in and completing the study Any medical condition associated with high medical risk or contraindicated to use chemotherapeutic agents as indicated in current product package insert Pregnant or nursing (lactating) women; women or men not willing to use a highly effective methods of contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vincristin, CCNU, cis-platin<br>radiotherapy and concomitant chemotherapy (7 cycles of 7 days): 2 mg/m2 vincristin i.v. 55,0 Gy Posterior cranial fossa (M0) 55,0 Gy Posterior cranial fossa / cerebral metastases + 49,6 Gy spinal metastases (M1-M3) maintenance chemotherapy (8 cycles of 42 days): once at day 1 at each cycle: 70 mg/m2 cis-platin i.v. 75 mg/m2 CCNU oral 2 mg/m2 vincristin i.v. once at day 8 and 15 at each cycle: 2 mg/m2 vincristin i.v. | Drug: maintenance chemotherapy (vincristin, cisplatin and CCNU)<br>* maintenance chemotherapy of maximum of 8 cycles á 42 days<br>* Other names: cis-platin: L01XA01;Radiation: Radiotherapy<br>* Radiotherapy of the partial brain<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility of the adjuvant chemotherapy | The main objective is the feasibility of the adjuvant chemotherapy which has gained the best results when combined with radiotherapy so far. The present protocol is primarily to determine the number of interruptions of the maintenance chemotherapy due to toxicity and the kind of toxicity . | participants will be followed for the duration of chemo therapy, an expected average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of performable cycles in chemo therapy | It should be determined how many cycles in the maintenance chemotherapy are feasible. | participants will be followed for the duration of chemo therapy, an expected average of 6 months | 
| 3 and 5 years progression-free survival | The 3 and 5-years rate of progression-free survival (pfs) should be determined for adult patients. | participants will be followed for the duration of chemo therapy and in the follow-up periode, an expected average of 3 to 5 years | 
| event-free survival | The event-free survival (efs) should be determined for adult patients. | participants will be followed for the duration of chemo therapy and in the follow-up periode, an expected average of 3 to 5 years | 
| overall survival | The overall survival (os) should be determined for adult patients. | participants will be followed for the duration of chemo therapy and in the follow-up periode, an expected average of 3 to 5 years | 
| course of cognitive performance/QoL | The course of the cognitive performance and the quality of life should be observed. | participants will be followed for the duration of chemo therapy and in the follow-up periode, an expected average of 3 to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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medulloblastoma, CNS, malignant neoplasm, NOA, neuroectodermal tumor, Vincristin, CCNU, Cisplatin