Histologically Confirmed MedulloblastomaPhase 1/2NCT01601184

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

A Phase 1/2 study testing vismodegib and Temozolomide in people with Histologically Confirmed Medulloblastoma and Activation of the Sonic Hedgehog (SHH) Pathway, run by Centre Leon Berard at 15 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Histologically Confirmed Medulloblastoma, Activation of the Sonic Hedgehog (SHH) Pathway
What is being tested?: vismodegib and Temozolomide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 15 sitesin 4 countries
Study dates: Jun 2012to Oct 2017
Phase: Phase 1/2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age ≥ 18 years
Patients must have histologically confirmed medulloblastoma (including posterior fossa primitive neuroectodermal tumor) for which no known curative therapy exists
Patients must have recurrent or refractory disease
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.
Activation of the SHH pathway validated by IHC.
ECOG performance status 0, 1 or 2

Show all 19Show fewer

Life expectancy ≥ 12 weeks
Patients must have normal organ and marrow function as defined below:
Neutrophils ≥ 1. 5 G/L Platelets ≥ 100 G /L Hemoglobin ≥ 10g/dL Creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula or MDRD formula for patients older than 65 years ) or serum creatinine within normal limits or less than 1.5 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 ULN ALAT and ASAT ≤ 2.5 ULN Serum albumin ≥ 25 g/L.
Patients recovered from prior treatment-related toxicity (persistent treatment related toxicity <Grade 2 are allowed (NCI-CTCAE v4.0).
Prior therapy:
No prior hedgehog antagonist vismodegib or other antagonists of the hedgehog pathway, and no prior temozolomide treatment for patients to be randomized in Arm A or B. Patients previously treated with temozolomide are eligible for enrollment in study arm C on a case by case basis and following sponsor agreement 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)
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).
: Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential:
≥50 years old and naturally amenorrheic for ≥ 1 year Permanent premature ovarian failure confirmed by a specialist gynaecologist Previous bilateral salpingo-oophorectomy XY 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.
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 4 for acceptable method of contraception) at least 4 weeks prior to study entry, during the study period and for at least 24 months post-treatment for women and 2 months post-treatment for men. Prior to dispensing vismodegib, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of vismodegib.
Ability to understand and willingness to comply to follow-up visits.
Covered by a medical insurance (in countries where applicable)

Who cannot join

Tumor tissue sample not available for biological studies (from the initial diagnosis and/or relapse)
Pregnant or breastfeeding women are not eligible.
History of allergic reactions attributed to compounds of similar chemical composition to vismodegib.
Any contraindications to temozolomide treatment as per Temodal® SPC (see Appendix 5).
Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption. Patients must be able to swallow capsules.
Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia, defined as less than the lower limit of normal despite adequate electrolyte supplementation.

Show all 11Show fewer

History of congestive heart failure.
History of ventricular arrhythmia requiring medication.
Congenital long QT syndrome.
Clinically significant unrelated systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results.
Patients using prohibited concomitant and/or concurrent medications (see section "Prohibited concomitant/concurrent treatments.)

Trial locations and contacts

15 sites in 4 countries.

Country

City, postcode or hospital

15 sites in 4 countries

France10 sites

Institut de Cancérologie de l'Ouest - Paul Papin
Angers, 49933
Institut Bergonié
Bordeaux, 33076
CHRU de Lille
Lille, Nord, 59037
CHBS Hôpital du Scorff
Lorient, Morbihan, 56322
Centre Léon Bérard
Lyon, Rhone, 69373
CHU La Timone
Marseille, Bouches Du Rhône, 13385
Hopital Central de Nancy
Nancy, Meurthe Et Moselle, 54035
Hopital de La Pitié Salpétrière
Paris, Île-de-France Region, 75013
Institut de Cancérologie de l'Ouest - René Gauducheau
Saint-Herblain, Loire Atlantique, 44805
Institut Claudius Régaud (iuct-oncopole)
Toulouse, Haute-Garonne, 31059

Other trials in France

Italy2 sites

BELLARIA Ospedale
Bologna, 40139
University of Turin
Torino, 10126

Other trials in Italy

Switzerland2 sites

Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, CH-8091
University Hospital Zurich
Zurich, CH-8091

Other trials in Switzerland

United Kingdom1 site

University College London Hospital - Mount Vernon Cancer Centre - Mount Vernon hospital
London, London-NW1-2PG

Other trials in United Kingdom

About this study

Official title: 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

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

38 patients will be included in the study.

Read the detailed description

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.

Conditions: Histologically Confirmed Medulloblastoma, Activation of the Sonic Hedgehog (SHH) Pathway
Being tested: vismodegib, Temozolomide
Keywords: medulloblastoma, sonic hedgehog pathway, vismodegib
Medical subject headings: Microphthalmia, Isolated, with Coloboma 5, Medulloblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

vismodegibDrug
Hedgehog pathway antagonist Dosage: 150 mg orally with or without food at the same time every day
TemozolomideDrug
Also called temodal
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

Study groups in NCT01601184
Study group	Role	What they receive
combination of vismodegib with temozolomide	Experimental	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) Receives: Drug: vismodegib; Drug: Temozolomide
temozolomide alone	Active comparator	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). Receives: Drug: Temozolomide
vismodegib alone	Other	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 Receives: Drug: vismodegib

What is being measured

The primary outcome is the main question the study is designed to answer.

To evaluate the safety of a fixed dose of vismodegib in combination with (phase I)temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma
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.
Measured: during the first three months follow up
To estimate the efficacy of vismodegib in combination with temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma (phase II)
the 6-month progression-free rate
Measured: 6 months after start of treatment

Secondary outcomes (7)

To collect preliminary results on the 6-month progression-free rate of the combination vismodegib + temozolomide (phase I)
measurement of progression free rate
Measured: 6 months after start of treatment
To estimate in the two study arms the objective response rate after 6 months of treatment (phase II)
measure by objective response rate
Measured: after 6 months of treatment
To estimate in the two study arms the duration of treatment response (phase II)
treatment response
Measured: one year
To estimate in the two study arms the best overall response obtained during the study (phase II)
Measured: one year
To estimate in the two study arms the progression-free survival (PFS)(phase II)
measure of progression free rate
Measured: one year
To estimate in the two study arms the time to treatment failure (phase II)
Measured: one year
frequency of adverse events based on the common toxicity criteria (CTC-AE-V4.0) grade
In the combination arm (vismodegib + temozolomide): to further evaluate the safety of the combination
Measured: one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Oct 2017

First posted17 May 2012 (estimated)
Study startJun 2012
Primary completionSep 2017
Study completionOct 2017

Why it stopped: The number of successes is not reached at the end of first stage of the phase II. The study is stopped.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (33)Papers the sponsor has linked to this study.
Other trials for Histologically Confirmed MedulloblastomaStudies of the same condition, open and under way.
More trials run by Centre Leon BerardThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01601184
Sponsor's protocol ID: MEVITEM
Other IDs: 2011-003372-37
Status last verified: May 2019
First submitted: 15 May 2012
Last updated: 21 May 2019
Results posted: No
Data monitoring committee: Yes

Publications

Lupi O. Correlations between the Sonic Hedgehog pathway and basal cell carcinoma. Int J Dermatol. 2007 Nov;46(11):1113-7. doi: 10.1111/j.1365-4632.2007.03391.x.
PubMed 17988327
Romer JT, Kimura H, Magdaleno S, Sasai K, Fuller C, Baines H, Connelly M, Stewart CF, Gould S, Rubin LL, Curran T. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice. Cancer Cell. 2004 Sep;6(3):229-40. doi: 10.1016/j.ccr.2004.08.019.
PubMed 15380514
Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, Marshall D, Fu L, Januario T, Kallop D, Nannini-Pepe M, Kotkow K, Marsters JC, Rubin LL, de Sauvage FJ. A paracrine requirement for hedgehog signalling in cancer. Nature. 2008 Sep 18;455(7211):406-10. doi: 10.1038/nature07275. Epub 2008 Aug 27.
PubMed 18754008
Cornu P, Chatellier G, Fauchon F, Foncin JF, Faillot T, Dorwling-Carter D, Philippon J. [The prognosis of medulloblastoma in adults]. Neurochirurgie. 1990;36(4):218-24. French.
PubMed 2277658
Coulbois S, Civit T, Grignon Y, Taillandier L, Girard F, Marchal C, Pinelli C, Auque J. [Adult medulloblastoma. Review of 22 patients]. Neurochirurgie. 2001 Feb;47(1):6-12. French.
PubMed 11283450
Giordana MT, Schiffer P, Lanotte M, Girardi P, Chio A. Epidemiology of adult medulloblastoma. Int J Cancer. 1999 Mar 1;80(5):689-92. doi: 10.1002/(sici)1097-0215(19990301)80:53.0.co;2-g.
PubMed 10048968
Brandes AA, Palmisano V, Monfardini S. Medulloblastoma in adults: clinical characteristics and treatment. Cancer Treat Rev. 1999 Feb;25(1):3-12. doi: 10.1053/ctrv.1998.0096.
PubMed 10212586
Chan AW, Tarbell NJ, Black PM, Louis DN, Frosch MP, Ancukiewicz M, Chapman P, Loeffler JS. Adult medulloblastoma: prognostic factors and patterns of relapse. Neurosurgery. 2000 Sep;47(3):623-31; discussion 631-2. doi: 10.1097/00006123-200009000-00018.
PubMed 10981749
del Charco JO, Bolek TW, McCollough WM, Maria BL, Kedar A, Braylan RC, Mickle JP, Buatti JM, Mendenhall NP, Marcus RB Jr. Medulloblastoma: time-dose relationship based on a 30-year review. Int J Radiat Oncol Biol Phys. 1998 Aug 1;42(1):147-54. doi: 10.1016/s0360-3016(98)00197-7.
PubMed 9747832
Duffner PK. Long-term effects of radiation therapy on cognitive and endocrine function in children with leukemia and brain tumors. Neurologist. 2004 Nov;10(6):293-310. doi: 10.1097/01.nrl.0000144287.35993.96.
PubMed 15518596
Padovani L, Sunyach MP, Perol D, Mercier C, Alapetite C, Haie-Meder C, Hoffstetter S, Muracciole X, Kerr C, Wagner JP, Lagrange JL, Maire JP, Cowen D, Frappaz D, Carrie C. Common strategy for adult and pediatric medulloblastoma: a multicenter series of 253 adults. Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):433-40. doi: 10.1016/j.ijrobp.2006.12.030.
PubMed 17498567
Abacioglu U, Uzel O, Sengoz M, Turkan S, Ober A. Medulloblastoma in adults: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys. 2002 Nov 1;54(3):855-60. doi: 10.1016/s0360-3016(02)02986-3.
PubMed 12377339
Carrie C, Lasset C, Alapetite C, Haie-Meder C, Hoffstetter S, Demaille MC, Kerr C, Wagner JP, Lagrange JL, Maire JP, et al. Multivariate analysis of prognostic factors in adult patients with medulloblastoma. Retrospective study of 156 patients. Cancer. 1994 Oct 15;74(8):2352-60. doi: 10.1002/1097-0142(19941015)74:83.0.co;2-h.
PubMed 7922986
Evans AE, Jenkin RD, Sposto R, Ortega JA, Wilson CB, Wara W, Ertel IJ, Kramer S, Chang CH, Leikin SL, et al. The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg. 1990 Apr;72(4):572-82. doi: 10.3171/jns.1990.72.4.0572.
PubMed 2319316
Packer RJ, Sutton LN, Elterman R, Lange B, Goldwein J, Nicholson HS, Mulne L, Boyett J, D'Angio G, Wechsler-Jentzsch K, et al. Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg. 1994 Nov;81(5):690-8. doi: 10.3171/jns.1994.81.5.0690.
PubMed 7931615

Study at a glance

From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT01601184
Acronym / sponsor ID: MEVITEM
Conditions: Histologically Confirmed Medulloblastoma, Activation of the Sonic Hedgehog (SHH) Pathway
Keywords: medulloblastoma, sonic hedgehog pathway, vismodegib
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The number of successes is not reached at the end of first stage of the phase II. The study is stopped.
Enrolment: 24 participants (actual)
Lead sponsor: Centre Leon BerardUniversity, hospital or other
Collaborators: Ministry of Health, France
Study start: Jun 2012
Primary completion: Sep 2017 (actual)
Study completion: Oct 2017 (actual)
First posted: 17 May 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

38 patients will be included in the study.

Detailed description

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
combination of vismodegib with temozolomide	Experimental	Drug: vismodegib, Drug: TemozolomideIn 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)
temozolomide alone	Active comparator	Drug: TemozolomideIn 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).
vismodegib alone	Other	Drug: vismodegibConsidering 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

Age ≥ 18 years
Patients must have histologically confirmed medulloblastoma (including posterior fossa primitive neuroectodermal tumor) for which no known curative therapy exists
Patients must have recurrent or refractory disease
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.
Activation of the SHH pathway validated by IHC.

Key exclusion criteria (11 listed)

Tumor tissue sample not available for biological studies (from the initial diagnosis and/or relapse)
Pregnant or breastfeeding women are not eligible.
History of allergic reactions attributed to compounds of similar chemical composition to vismodegib.
Any contraindications to temozolomide treatment as per Temodal® SPC (see Appendix 5).
Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption. Patients must be able to swallow capsules.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
vismodegibHedgehog pathway antagonist Dosage: 150 mg orally with or without food at the same time every day	Drug	combination of vismodegib with temozolomide, vismodegib alone
TemozolomideAlso: temodalalkylating 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	Drug	combination of vismodegib with temozolomide, temozolomide alone

Primary outcome

To evaluate the safety of a fixed dose of vismodegib in combination with (phase I)temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma
Time frame: during the first three months follow up
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.
To estimate the efficacy of vismodegib in combination with temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma (phase II)
Time frame: 6 months after start of treatment
the 6-month progression-free rate

7 secondary outcomes

To collect preliminary results on the 6-month progression-free rate of the combination vismodegib + temozolomide (phase I)
Time frame: 6 months after start of treatment
To estimate in the two study arms the objective response rate after 6 months of treatment (phase II)
Time frame: after 6 months of treatment
To estimate in the two study arms the duration of treatment response (phase II)
Time frame: one year
To estimate in the two study arms the best overall response obtained during the study (phase II)
Time frame: one year
To estimate in the two study arms the progression-free survival (PFS)(phase II)
Time frame: one year
To estimate in the two study arms the time to treatment failure (phase II)
Time frame: one year
frequency of adverse events based on the common toxicity criteria (CTC-AE-V4.0) grade
Time frame: one year

Results and safety

The study was stopped early (reason given: The number of successes is not reached at the end of first stage of the phase II. The study is stopped.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2019.
Background: PubMed 17988327Lupi O. Correlations between the Sonic Hedgehog pathway and basal cell carcinoma. Int J Dermatol. 2007 Nov;46(11):1113-7. doi: 10.1111/j.1365-4632.2007.03391.x.
Background: PubMed 15380514Romer JT, Kimura H, Magdaleno S, Sasai K, Fuller C, Baines H, Connelly M, Stewart CF, Gould S, Rubin LL, Curran T. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice. Cancer Cell. 2004 Sep;6(3):229-40. doi: 10.1016/j.ccr.2004.08.019.
Background: PubMed 18754008Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, Marshall D, Fu L, Januario T, Kallop D, Nannini-Pepe M, Kotkow K, Marsters JC, Rubin LL, de Sauvage FJ. A paracrine requirement for hedgehog signalling in cancer. Nature. 2008 Sep 18;455(7211):406-10. doi: 10.1038/nature07275. Epub 2008 Aug 27.
Background: PubMed 2277658Cornu P, Chatellier G, Fauchon F, Foncin JF, Faillot T, Dorwling-Carter D, Philippon J. [The prognosis of medulloblastoma in adults]. Neurochirurgie. 1990;36(4):218-24. French.
Background: PubMed 11283450Coulbois S, Civit T, Grignon Y, Taillandier L, Girard F, Marchal C, Pinelli C, Auque J. [Adult medulloblastoma. Review of 22 patients]. Neurochirurgie. 2001 Feb;47(1):6-12. French.
Background: PubMed 10048968Giordana MT, Schiffer P, Lanotte M, Girardi P, Chio A. Epidemiology of adult medulloblastoma. Int J Cancer. 1999 Mar 1;80(5):689-92. doi: 10.1002/(sici)1097-0215(19990301)80:53.0.co;2-g.
Background: PubMed 10212586Brandes AA, Palmisano V, Monfardini S. Medulloblastoma in adults: clinical characteristics and treatment. Cancer Treat Rev. 1999 Feb;25(1):3-12. doi: 10.1053/ctrv.1998.0096.
Background: PubMed 10981749Chan AW, Tarbell NJ, Black PM, Louis DN, Frosch MP, Ancukiewicz M, Chapman P, Loeffler JS. Adult medulloblastoma: prognostic factors and patterns of relapse. Neurosurgery. 2000 Sep;47(3):623-31; discussion 631-2. doi: 10.1097/00006123-200009000-00018.
Background: PubMed 9747832del Charco JO, Bolek TW, McCollough WM, Maria BL, Kedar A, Braylan RC, Mickle JP, Buatti JM, Mendenhall NP, Marcus RB Jr. Medulloblastoma: time-dose relationship based on a 30-year review. Int J Radiat Oncol Biol Phys. 1998 Aug 1;42(1):147-54. doi: 10.1016/s0360-3016(98)00197-7.
Background: PubMed 15518596Duffner PK. Long-term effects of radiation therapy on cognitive and endocrine function in children with leukemia and brain tumors. Neurologist. 2004 Nov;10(6):293-310. doi: 10.1097/01.nrl.0000144287.35993.96.
Background: PubMed 17498567Padovani L, Sunyach MP, Perol D, Mercier C, Alapetite C, Haie-Meder C, Hoffstetter S, Muracciole X, Kerr C, Wagner JP, Lagrange JL, Maire JP, Cowen D, Frappaz D, Carrie C. Common strategy for adult and pediatric medulloblastoma: a multicenter series of 253 adults. Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):433-40. doi: 10.1016/j.ijrobp.2006.12.030.
Background: PubMed 12377339Abacioglu U, Uzel O, Sengoz M, Turkan S, Ober A. Medulloblastoma in adults: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys. 2002 Nov 1;54(3):855-60. doi: 10.1016/s0360-3016(02)02986-3.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

didier frappaz principal investigator

Centre Léon Bérard, Lyon

15 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in France, Italy, Switzerland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The number of successes is not reached at the end of first stage of the phase II. The study is stopped.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the safety of a fixed dose of vismodegib in combination with (phase I)temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma (time frame: during the first three months follow up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01601184, which also lists 33 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2019.