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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04402073


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04402073
Ethics application status
Date submitted
1/04/2020
Date registered
26/05/2020
Date last updated
11/12/2023

Titles & IDs
Public title
Personalized Risk-Adapted Therapy in Post-Pubertal Patients With Newly-Diagnosed Medulloblastoma
Scientific title
Personalized Risk-Adapted Therapy in Post-Pubertal Patients With Newly-Diagnosed Medulloblastoma (PersoMed-I)
Secondary ID [1] 0 0
1634
Universal Trial Number (UTN)
Trial acronym
PersoMed-I
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medulloblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sonidegib
Treatment: Drugs - Cisplatin
Treatment: Drugs - Lomustine
Treatment: Drugs - Vincristine
Treatment: Other - radiotherapy

Other: standard arms - Criteria: Adult SHH (p53wt) M0-1, adult WNT M0-1, adult Group 4 M0-1.
Radiotherapy to the cranio-spinal axis of 35.2 Gy in 22 daily fractions of 1.6 Gy, followed by an additional boost to the tumour site of 19.8 Gy in 11 daily fractions of 1.8 Gy, summing up to a total dose of 55.0 Gy in 33 daily fractions of 1.6/1.8 Gy.
Criteria: Post pubertal < 18 y SHH (p53wt) M0.
Radiotherapy to the cranio-spinal axis of 23.4 Gy in 13 daily fractions of 1.8 Gy, followed by an additional boost to the tumour site of 30.6 Gy in 17 daily fractions of 1.8 Gy, summing up to a total dose of 54.0 Gy in 30 daily fractions of 1.8 Gy.

Experimental: experimental arms - Radiotherapy Criteria: Adult and post-pubertal SHH (p53wt) M0; adult WNT M0, adult Group 4 M0.
Radiotherapy to the cranio-spinal axis of 23.4 Gy in 13 daily fractions of 1.8 Gy, followed by an additional boost to the tumour site of 30.6 Gy in 17 daily fractions of 1.8 Gy, summing up to a total dose of 54.0 Gy in 30 daily fractions of 1.8 Gy.
SMO-inhibitor Criteria: Adult and post-pubertal SHH (p53wt) M0.
Sonidegib 200 mg/day (daily) from first day of radio-chemotherapy until end of maintenance chemotherapy, including 6w chemotherapy break.


Treatment: Drugs: Sonidegib
Sonidegib is a selective smoothened inhibitor that inhibits the sonic hedgehog-signaling pathway. It is used in patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.

Treatment: Drugs: Cisplatin
Cisplatin (CIS) is a platinum derivate used in the treatment in several epithelial tumours. The application route is through the veins.

Treatment: Drugs: Lomustine
Lomustine is a nitrosourea used in the treatment of brain tumours and Hodgkin's disease. The application route is oral.

Treatment: Drugs: Vincristine
Vincristine sulfate (VCR) is an inhibitor of microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Vincristine sulfate is indicated in acute leukemia, Hodgkin's disease, non-Hodgkin's lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor. The application route is through the vein.

Treatment: Other: radiotherapy
Radiotherapy to the cranio-spinal axis of 35.2 Gy in 22 daily fractions of 1.6 Gy, followed by an additional boost to the tumour site of 19.8 Gy in 11 daily fractions of 1.8 Gy, summing up to a total dose of 55.0 Gy in 33 daily fractions of 1.6/1.8 Gy.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
91 months after the date of recruitment of the first patient
Secondary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
when 43 PFS events are observed which is estimated to occur 91 months after the date of recruitment of the first patient.
Secondary outcome [2] 0 0
overall survival (OV)
Timepoint [2] 0 0
when 43 PFS events are observed which is estimated to occur 91 months after the date of recruitment of the first patient.
Secondary outcome [3] 0 0
safety and tolerability profile: CTCAE
Timepoint [3] 0 0
when 43 PFS events are observed which is estimated to occur 91 months after the date of recruitment of the first patient.
Secondary outcome [4] 0 0
health-related quality of life (HRQoL)
Timepoint [4] 0 0
when 43 PFS events are observed which is estimated to occur 91 months after the date of recruitment of the first patient.
Secondary outcome [5] 0 0
overall survival
Timepoint [5] 0 0
when 43 PFS events are observed which is estimated to occur 91 months after the date of recruitment of the first patient.

Eligibility
Key inclusion criteria
- Newly diagnosed, histologically proven, genetically classified, centrally confirmed
medulloblastoma (WNT M0-1, SHH M0-1 (p53wt), Group 4 M0-1)

- Molecular subtype: medulloblastoma, SHH-activated and TP53-wildtype, M0-1;
medulloblastoma, WNT-activated, M0-1; medulloblastoma, Group 4, M0-1

- Histologic subtype: medulloblastoma, classic (CMB); medulloblastoma,
desmoplastic/nodular (DNMB); medulloblastoma, with extensive nodularity (MBEN);
medulloblastoma, large cell/anaplastic (LCA)

- Adult (18 years and above): in WNT-activated and Group 4 medulloblastoma

- Post-pubertal, defined as females with a bone age of at least 15 years and males with
a bone age of at least 17 years, or adult (greater than 18 y of age) (see appendix N)
in SHH-activated and TP53-wildtype medulloblastoma

- Availability of prognostic markers (MYC/MYCN amplification, MYC/MYCN mutation)

- Availability of paraffin embedded tumour tissue (FFPE) (1 block or 30 unstained
slides) and whole blood sample (10 ml) for central review

- For patients with SHH activated tumours: exclusion of germline alteration of TP53,
PTCH, SUFU, BRCA2 and PALB2 if known before randomization

- Clinical status within 2 weeks of randomization: Karnofsky 50-100. NANO-score 0 to 9
(allowing full-blown cerebellar symptoms)

- Clinically standard-risk (centrally assessed MRI review) defined as: 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 M0-1 with no clinical evidence of
extra-CNS metastasis

- Full recovery from surgery or any post-surgical complication (e.g. Bleeding,
infections etc)

- Pre-surgery and/or post-surgery MRI available.

- Baseline brain MRI and spinal MRI available within 2 weeks of randomization.

- Normal liver, renal and haematological function within 2 weeks of randomization.

- WBC greater than or equal to 3×10^9/L

- ANC greater than or equal to 1.5×10^9/L

- Platelet count of greater than or equal to 100×10^9/L independent of transfusion

- Hemoglobin greater than or equal to 10 g/dl

- Total Bilirubin less than or equal to 1.5 ULN

- ALT (SGPT), AST (SGOT), alkaline phosphatase (ALP) less than or equal to 2.5 × ULN

- Serum creatinine less than 1.5 x ULN or creatinine clearance (CrCl) greater than 30
mL/min (using the Cockcroft-Gault formula)

- Negative serum or urine pregnancy test within 7 days of randomization for WOCBP.

- Patients of childbearing / reproductive potential (WOCBP) must use two methods of
adequate birth control, including a highly effective method and a barrier method
during the study treatment period and for at least 20 months after the last study
treatment is mandatory for the patients that received sonidegib, for all other
patients this period is at least 6 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. Male patients even
those who have had a vasectomy must always use a condom during treatment and for 6
months after last treatment. Men should not donate semen during treatment and for at
least 6 months after ending treatment (donation of semen for the semen analyses of the
fertility project 1 b is allowed). Appendix H.

- 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.

- Before patient registration/randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations. For patients less than 18 years
of age, consent has to be obtained from the parent(s) or legal representative.
Minimum age
15 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment for medulloblastoma

- Unavailability of central review pathology results.

- Inability to start radiotherapy within 43 days of surgery

- Significant sensorineural hearing deficit as defined by pure tone audiometry with bone
conduction or air conduction and normal tympanogram showing impairment greater than or
equal to 20 dB at 1-3 kHz

- Any medical contraindication to radiotherapy or chemotherapy.

- Hypersensitivity to contrast medium for MRI.

- Hypersensitivity towards the active substance of any of study drugs or their
excipients

- Prior or current use of mitoxantrone, methotrexate, topotecan, imatinib, irinotecan or
statins

- 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

- 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 less than or equal to 6 and PSA less than 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

- Known history or current evidence of active Hepatitis B (e.g., positive HBV surface
antigen) or C (e.g., HCV RNA [qualitative] is detected)

- Known or current evidence of Human Immunodeficiency Virus (HIV) infection (positive
HIV-1/2 antibodies)

- 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.

Study design
Purpose of the study
Health Services Research
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2030
Actual
Sample size
Target
205
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - University Of Queensland - Brisbane
Recruitment hospital [3] 0 0
Austin Health - Austin hospital - Melbourne
Recruitment hospital [4] 0 0
Peter Maccallum Cancer Institute - Melbourne
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [6] 0 0
John Hunter Children's Hospital - New Lambton Heights
Recruitment hospital [7] 0 0
Prince Of Wales Hospital - Sydney
Recruitment hospital [8] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [9] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [10] 0 0
Westmead Hospital - Crown Princess Mary Cancer Center - Westmead
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Nedlands
Recruitment postcode(s) [5] 0 0
- New Lambton Heights
Recruitment postcode(s) [6] 0 0
- Sydney
Recruitment postcode(s) [7] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Innsbruck
Country [2] 0 0
Austria
State/province [2] 0 0
Wien
Country [3] 0 0
France
State/province [3] 0 0
Lille
Country [4] 0 0
France
State/province [4] 0 0
Lyon
Country [5] 0 0
France
State/province [5] 0 0
Marseille
Country [6] 0 0
France
State/province [6] 0 0
Nice
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
France
State/province [8] 0 0
Saint-Herblain
Country [9] 0 0
France
State/province [9] 0 0
Toulouse
Country [10] 0 0
Germany
State/province [10] 0 0
Bochum
Country [11] 0 0
Germany
State/province [11] 0 0
Bonn
Country [12] 0 0
Germany
State/province [12] 0 0
Dresden
Country [13] 0 0
Germany
State/province [13] 0 0
Erfurt
Country [14] 0 0
Germany
State/province [14] 0 0
Essen
Country [15] 0 0
Germany
State/province [15] 0 0
Frankfurt
Country [16] 0 0
Germany
State/province [16] 0 0
Freiburg
Country [17] 0 0
Germany
State/province [17] 0 0
Goettigen
Country [18] 0 0
Germany
State/province [18] 0 0
Hamburg
Country [19] 0 0
Germany
State/province [19] 0 0
Heidelberg
Country [20] 0 0
Germany
State/province [20] 0 0
Leipzig
Country [21] 0 0
Germany
State/province [21] 0 0
Mainz
Country [22] 0 0
Germany
State/province [22] 0 0
Mannheim
Country [23] 0 0
Germany
State/province [23] 0 0
Munich
Country [24] 0 0
Germany
State/province [24] 0 0
Regensburg
Country [25] 0 0
Germany
State/province [25] 0 0
Tuebingen
Country [26] 0 0
Italy
State/province [26] 0 0
Bologna
Country [27] 0 0
Italy
State/province [27] 0 0
Florence
Country [28] 0 0
Italy
State/province [28] 0 0
Milano
Country [29] 0 0
Italy
State/province [29] 0 0
Torino
Country [30] 0 0
Italy
State/province [30] 0 0
Treviso
Country [31] 0 0
Netherlands
State/province [31] 0 0
Groningen
Country [32] 0 0
Netherlands
State/province [32] 0 0
Rotterdam
Country [33] 0 0
Spain
State/province [33] 0 0
Badalona
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid
Country [36] 0 0
Switzerland
State/province [36] 0 0
Lausanne
Country [37] 0 0
Switzerland
State/province [37] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Other
Name
European Organisation for Research and Treatment of Cancer - EORTC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Medulloblastoma is a rare brain malignancy, mainly affecting children. Treatment of this
rapidly growing tumor begins with maximal surgical removal plus radiation and chemotherapy.
Treatment toxicity is high. Post-pubertal and pediatric medulloblastomas are biologically and
prognostically different, which mandates age-adapted treatment strategies. Patients after
puberty bear an intermediate to high prognostic risk. This means that a large number of these
patients, are faced with death and/or disability (mainly neurocognitive). Therefore, the
scientific and medical need is high. One of the genetic subgroups of medulloblastoma, the
SHH-subgroup (Sonic HedgeHog- subgroup), is highly overrepresented in medulloblastoma
patients after puberty. This subgroup can be treated with a targeted therapy. The
investigators will therefore randomize patients and treat SHH-subgroup patients with
sonidegib and a reduction of radiotherapy dose in the experimental arm of the trial. The
hypothesis that this personalized risk-adapted therapy will improve outcomes in view of
increased efficacy and decreased toxicity.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04402073
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter Hau
Address 0 0
EORTC study coordinator
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
EORTC HQ
Address 0 0
Country 0 0
Phone 0 0
003227741611
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04402073

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 145
John Hunter Children's Hospital
Recruitment hospital [2] 146
Prince of Wales Hospital
Recruitment hospital [3] 147
Royal North Shore Hospital
Recruitment hospital [4] 148
Westmead Hospital
Recruitment hospital [5] 149
Sydney Children's Hospital
Recruitment hospital [6] 150
Princess Alexandra Hospital
Recruitment hospital [7] 151
Royal Brisbane & Womens Hospital
Recruitment hospital [8] 152
The Royal Adelaide Hospital
Recruitment hospital [9] 153
Austin Health - Austin Hospital
Recruitment hospital [10] 154
Peter MacCallum Cancer Centre
Recruitment hospital [11] 155
Sir Charles Gairdner Hospital
Recruitment postcode(s) [1] 146
2305
Recruitment postcode(s) [2] 147
2031
Recruitment postcode(s) [3] 148
2065
Recruitment postcode(s) [4] 149
2145
Recruitment postcode(s) [5] 150
4102
Recruitment postcode(s) [6] 151
4029
Recruitment postcode(s) [7] 152
5000
Recruitment postcode(s) [8] 153
3084
Recruitment postcode(s) [9] 154
3000
Recruitment postcode(s) [10] 155
6009
Funding & Sponsors
Funding source category [1] 57
Charities/Societies/Foundations
Name [1] 57
CanTeen
Address [1] 57
75 King Street Newtown NSW 2043
Country [1] 57
Australia
Funding source category [2] 58
Government body
Name [2] 58
Cancer Australia
Address [2] 58
14/300 Elizabeth Street Surry Hills NSW 2010
Country [2] 58
Australia
Funding source category [3] 65
Charities/Societies/Foundations
Name [3] 65
The Kids’ Cancer Project
Address [3] 65
Suite 1, Level 1/789 Botany Rd, Rosebery NSW 2018
Country [3] 65
Australia
Primary sponsor
Other Collaborative groups
Primary sponsor name
European Organisation for Research and Treatment of Cancer (EORTC)
Primary sponsor address
Avenue E. Mounierlaan 83/11
Brussel 1200 Bruxelles
België - Belgique
Primary sponsor country
Belgium
Secondary sponsor category [1] 60
University
Name [1] 60
The University of Sydney
Address [1] 60
Camperdown NSW 2006
Country [1] 60
Australia
Other collaborator category [1] 61
Other Collaborative groups
Name [1] 61
Cooperative Trials Group for Neuro-Oncology (COGNO)
Address [1] 61
NHMRC Clinical Trials Centre Level 4 92-94 Parramatta Road Camperdown NSW Australia 2050
Country [1] 61
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 41
Sydney Local Health District HREC (RPAH Zone)
Address [1] 41
Research Ethics and Governance Office Royal Prince Alfred Hospital Camperdown NSW 2050
Country [1] 41
Australia
Date submitted for ethics approval [1] 41
27/04/2021
Approval date [1] 41
09/06/2021
Ethics approval number [1] 41
 
Public notes

Contacts
Principal investigator
Title 293 0
Prof
Name 293 0
David Ziegler
Address 293 0
NHMRC Clinical Trials Centre, University of Sydney Lifehouse Level 6 119–143 Missenden Road, Camperdown NSW 2050
Country 293 0
Australia
Phone 293 0
+61 02 9382 1730
Fax 293 0
Email 293 0
[email protected]
Contact person for public queries
Title 294 0
Ms
Name 294 0
PersoMed-I Trial Coordinator
Address 294 0
NHMRC Clinical Trials Centre, University of Sydney Lifehouse Level 6 119–143 Missenden Road, Camperdown NSW 2050
Country 294 0
Australia
Phone 294 0
+61 02 9562 5000
Fax 294 0
Email 294 0
[email protected]
Contact person for scientific queries
Title 295 0
Ms
Name 295 0
PersoMed-I Trial Coordinator
Address 295 0
NHMRC Clinical Trials Centre, University of Sydney Lifehouse Level 6 119–143 Missenden Road, Camperdown NSW 2050
Country 295 0
Australia
Phone 295 0
+61 02 9562 5000
Fax 295 0
Email 295 0
[email protected]