Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Medulloblastoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Alkylating Agents

Antineoplastic Agents, Alkylating

In the first step of the study (Phase I), 9 adult patients with relapsing or refractory medulloblastoma will be randomized (randomization ratio 2:1) to receive

- Arm A: the combination of vismodegib (150 mg/day continuously) with temozolomide (150 mg/m2 during Cycle 1 \[day 1 to day 5/ 28 day-cycle\] and 200 mg/m2 during subsequent cycles) (6 patients)

In the first step of the study (Phase I), 9 adult patients with relapsing or refractory medulloblastoma will be randomized (randomization ratio 2:1) to receive Arm B: temozolomide alone (150 mg/m2 day1 to day 5/ 28 day-cycle during Cycle 1 and 200 mg/m2 day 1 to day 5/ 28 day-cycle during subsequent cycles) (3 patients).

Considering the rarity of the disease, the few therapeutic options available and the promising results reported with vismodegib in adult medulloblastoma : the Sponsor will consider (on case by case basis) the enrolment of patients previously treated by temozolomide in a 3rd independent and parallel study arm

Hedgehog pathway antagonist Dosage: 150 mg orally with or without food at the same time every day

vismodegib

alkylating agent Dosage: Dose in Cycle 1 is 150 mg/m2 orally once daily for 5 days followed by 23 days without treatment. At the start of Cycle 2, the dose is escalated to 200mg/m2 orally once daily for 5 days

didier frappaz

The purpose of this study is to evaluate the safety of vismodegib in combination with temozolomide (primary objective - phase I) and to estimate the efficacy of vismodegib in combination with temozolomide in adult patients with recurrent, progressive, or refractory medulloblastomas to standard therapy measured by the 6-month progression-free rate (phase II).

This study is an open-label Phase I/II, international, randomized.

38 patients will be included in the study.

Secondary objectives are :

phase I : to collect preliminary results on the 6-month progression-free rate of the combination vismodegib + temozolomide

PHASE II

To estimate in the two study arms:

* the objective response rate (Complete response + Partial Response according to WHO criteria) after 6 months of treatment
* the duration of treatment response
* the best overall response obtained during the study
* the progression-free survival (PFS)
* the time to progression (TTP)
* the time to treatment failure (TTF)
* In the combination arm (vismodegib + temozolomide): to further evaluate the safety of the combination.

Study of Vismodegib in Combination With Temozolomide Versus Temozolomide Alone in Patients With Medulloblastomas With an Activation of the Sonic Hedgehog Pathway

An International, Randomized, Open-label Phase I/II Study of Vismodegib in Combination With Temozolomide Versus Temozolomide Alone in Adult Patients With Recurrent or Refractory Medulloblastomas Presenting an Activation of the Sonic Hedgehog (SHH) Pathway

number of severe toxicities occurring during the first 3 months of follow-up :

* Toxic death
* Grade 4 toxicity
* Any grade 3 AE leading to study treatment interruption for more than 7 days or discontinuation.

In the combination arm (vismodegib + temozolomide): to further evaluate the safety of the combination

Spots Global Cancer Trial Database for activation of the sonic hedgehog (shh) pathway