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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/NCT05830084
Additional trial details provided through ANZCTR are available at the end of this record.
Registration number
NCT05830084
Ethics application status
Date submitted
1/05/2023
Date registered
13/04/2023
Date last updated
10/05/2023
Titles & IDs
Public title
Phase Ib / Regorafenib With Conventional Chemotherapy/Newly Diagnosed Patients/ Multimetastatic Ewing Sarcoma
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Scientific title
Phase Ib Study of the Combination of Regorafenib With Conventional Chemotherapy for the Treatment of Newly Diagnosed Patients With Multimetastatic Ewing Sarcoma
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Secondary ID [1]
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2022/3545
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Secondary ID [2]
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2022-002874-10
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Universal Trial Number (UTN)
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Trial acronym
REGO-EWING
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Bone Cancer
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Condition category
Condition code
Cancer
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Sarcoma (also see 'Bone') - soft tissue
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Cancer
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Bone
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Cancer
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Children's - Other
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - regorafenib tablet
Experimental: Induction chemotherapy (VDC/IE) and local treatment /consolidation chemotherapy - Standard ES treatment consists of: induction chemotherapy (VDC/IE) and local treatment (surgery/radiotherapy), followed by consolidation chemotherapy (VC/IE)/ Bu-Mel (according to physician and patient choice).
Regorafenib will be administered during induction chemotherapy (VDC/IE) and during consolidation chemotherapy with conventional chemotherapy (VC/IE) but not Bu-Mel therapy Conventional chemotherapy will be administered at the recommended dose (100%) and only regorafenib will be escalated/de-escalated.
Regorafenib will only be given concomitant to radiotherapy in case the primary tumor is located in the extremities. In case of primary tumors located in the pelvis, abdomen, thorax, spine, brain, head or neck, regorafenib will be stopped at least 1 week before start of radiotherapy.
Treatment: Drugs: regorafenib tablet
Regorafenib will be escalated/de-escalated, starting at DL0:
DL1: 82 mg/m^2 once daily for 21 days/28 days (max 160mg) (100% of the RP2D)
DL0 (starting dose): 66 mg/m^2 once daily for 21 days/28 days (max 120mg) (80% of the RP2D)
DL-1: 50 mg/m^2 once daily for 21 days/28 days (max 80mg) (60% of the RP2D)
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Occurrence of Dose-Limiting Toxicities (DLT)
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Assessment method [1]
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The dose-finding escalation will be driven by the occurrence of Dose-Limiting Toxicities (DLT), assessed over the first 28-day cycle (cycle 1), and defined as any of the following haematological and non-haematological events that occur during the DLT period (4 weeks after the start of treatment = cycle 1) and are at least possibly related (possibly, probably, or definitely) attributable to VDC/IE + regorafenib:
Any cardiac toxicity grade ≥ 3
Any grade 3 or 4 (hematological or non-hematological) toxicity leading to delay of start of next course by > 7 days (i.e: starting > day 21).
Any dose interruption or reduction due to toxicity which results in administration of less than 80% of the planned dosage of regorafenib or 75% of the planned dosage of chemotherapy.
Any grade 3 or 4 toxicity resulting in discontinuation of the new combination
Any grade 5 toxicity related to study treatment (death)
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Timepoint [1]
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28 days after the start of treatment
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Secondary outcome [1]
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Overall Survival (OS)
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Assessment method [1]
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Defined as the time from start of anti-cancer treatment to death, irrespective of the cause. Surviving patients will be censored at their last follow-up date
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Timepoint [1]
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Until 18 months after inclusion of the last patient
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Secondary outcome [2]
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Progression-Free Survival (PFS)
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Assessment method [2]
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Defined as the time from start of anti-cancer treatment to first event, where an event is progression without complete remission, recurrence following complete remission or death.
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Timepoint [2]
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Until 18 months after inclusion of the last patient
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Eligibility
Key inclusion criteria
1. Any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or
round cell sarcomas which are 'Ewing's-like' but negative for EWSR1 gene rearrangement
2. Metastatic disease
3. Age ≥2 years and <50 years (from second birthday to 49 years 364 days)
4. Patient assessed as medically fit to receive the Ewing sarcoma standard multimodal
treatment and regorafenib, including:
- Absolute Neutrophil Count (ANC) ≥ 0.75x10^9/L, platelets ≥ 75x10^9/L.
- Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 5×ULN
- Bilirubin ≤ 2×ULN
- Creatinine < 2x ULN or creatinine clearance >60 ml/min/1.73 m^2
- International normalized ratio (INR)/ Partial thromboplastin time (PTT). INR and
PTT ≤ 1.5 x ULN. INR & PTT ≤ 1.5xULN
5. Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF)
≥50%) at baseline, as determined by echocardiography
6. Adequately controlled blood pressure (BP) with or without antihypertensive
medications, defined as: a BP <95th percentile for sex, age, and height at screening
(as per National Heart Lung and Blood Institute [NHLBI] guidelines) and no change in
antihypertensive medications within 1 week prior to Cycle 1 Day 1. Patients >18 years
old should have BP ≤ 150/90 mmHg.
7. No prior treatment for Ewing sarcoma other than surgery
8. Negative pregnancy test for female patients of childbearing potential within 7 days
prior to study registration.
9. Patient agrees to use highly effective contraception during therapy and for 12 months
after last trial treatment (females) or 6 months after last trial treatment (males),
where applicable
10. Subject must be able to swallow and retain oral medication.
11. Written informed consent from the patient and/or the parent/legal guardian, according
to local, regional or national regulation prior to any study specific procedures.
12. Patients must be affiliated to a social security system or beneficiary of the same, as
per local regulatory requirements (France only)
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Minimum age
2
Years
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Maximum age
50
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
1. Localized tumor or metastatic disease to lung/pleura only.
2. Contra-indication to the Ewing sarcoma standard multimodal treatment
3. Pregnant or breastfeeding women or intending to become pregnant during the study.
4. Follow-up not possible due to social, geographic or psychological reasons
5. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter absorption of oral drugs
6. A clinically significant ECG abnormality, including a marked prolonged QTcF interval
(eg, a repeated demonstration of a QTcF interval >480 msec) Clinically significant,
uncontrolled heart disease (including history of any cardiac arrhythmias, e.g.,
ventricular, supraventricular, nodal arrhythmias, or conduction abnormality, unstable
angina, active coronary artery disease and myocardial infarction within 6 months
before randomization.) Uncontrolled hypertension (systolic pressure >150 mmHg or
diastolic pressure > 90 mmHg on repeated measurement) despite optimal medical
management
7. Previous arterial or venous thromboembolisms Grade ≥ 3 per CTCAE v5.0
8. Hypersensitivity to any active substance or to any excipients
9. Radiographic evidence of encasement or invasion of a major blood vessel or of
intratumoral cavitation
10. Major surgical procedure or significant traumatic injury within 28 days before
starting study treatment
11. Non-healing wound, ulcer or bone fracture.
12. Interstitial lung disease with ongoing signs and symptoms.
13. Any other medical or other condition that, in the opinion of the investigator(s),
would preclude the subject's participation in this clinical study
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
27/03/2023
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
27/03/2026
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Actual
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Sample size
Target
24
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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France
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State/province [1]
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Ile De France
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Funding & Sponsors
Primary sponsor type
Other
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Name
Gustave Roussy, Cancer Campus, Grand Paris
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Bayer
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
New drug efficacy in ES has been disappointing in the last decades and no new drugs have been
successfully introduced up to now in front line treatment. Among the tested drugs, early
clinical data suggest that strategies using multi-targeted tyrosine kinase inhibitors (TKI)
with anti-angiogenic activities are among the most efficient and may be beneficial in the
treatment of patients with ES.
Several TKI have been and are currently being tested as single-agent in patients with
relapsed/refractory ES with encouraging results in phase II trials. Regorafenib has shown
promising activity in Ewing sarcoma relapse setting, Nevertheless, regorafenib has never been
combined with the intensive chemotherapy VDC/IE schedule and therefore this combination needs
to be evaluated in order to avoid dose reduction of the current standard treatment and hence
its efficacy.
The current clinical trial has been therefore designed to test the feasibility of regorafenib
with ES conventional chemotherapy. It consists of a phase Ib that will only recruit patients
with multi-metastatic (other than lungs/pleura only) ES, that present the highest unmet
medical need (2 year EFS: 33%, similar to patients with relapse/refractory ES).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT05830084
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Trial related presentations / publications
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Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed
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Contacts
Principal investigator
Name
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Pablo Berlanga, MD
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Address
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Gustave Roussy, Cancer Campus, Grand Paris
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Pablo Berlanga, MD
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Address
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Country
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Phone
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+33 (0)1 42 11 41 67
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05830084
Additional trial details provided through ANZCTR
Accrual to date
4
Recruiting in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1]
164
Queensland Children's Hospital
Recruitment hospital [2]
165
Perth Children's Hospital
Recruitment hospital [3]
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Monash Children’s Hospital
Recruitment hospital [4]
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Chris O’Brien Lifehouse
Recruitment postcode(s) [1]
164
4101
Recruitment postcode(s) [2]
165
6009
Recruitment postcode(s) [3]
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3168
Recruitment postcode(s) [4]
167
2050
Funding & Sponsors
Funding source category [1]
91
Charities/Societies/Foundations
Name [1]
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The Australian Organisation for Young People Living with Cancer (Canteen)
Address [1]
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75 King St, Newtown NSW 2042 Australia
Country [1]
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Australia
Funding source category [2]
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Government body
Name [2]
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MRFF, Australian Department of Health
Address [2]
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Department of Health GPO Box 9848 Canberra ACT 2601 Australia
Country [2]
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Australia
Funding source category [3]
93
Charities/Societies/Foundations
Name [3]
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The Kid's Cancer Project
Address [3]
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Suite 1, Level 1/789 Botany Rd, Rosebery NSW 2018
Country [3]
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Australia
Funding source category [4]
94
Other Collaborative groups
Name [4]
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Australian and New Zealand Sarcoma Association
Address [4]
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VCCC Level 1 305 Grattan Street Melbourne Victoria 3000 Australia
Country [4]
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Australia
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australia and New Zealand Children's Haematology and Oncology Group (ANZCHOG)
Primary sponsor address
27-31 Wright St, Clayton VIC 3168
Primary sponsor country
Australia
Other collaborator category [1]
95
Hospital
Name [1]
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Gustave Roussy
Address [1]
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114 Rue Edouard Vaillant, 94805 Villejuif, France
Country [1]
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France
Ethics approval
Ethics application status
Approved
Ethics committee name [1]
68
The Child and Adolescent Health Service Human Research Ethics Committee
Address [1]
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15 Hospital Avenue Nedlands WA 6009
Country [1]
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Australia
Date submitted for ethics approval [1]
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11/07/2023
Approval date [1]
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14/08/2023
Ethics approval number [1]
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RGS0000006256
Public notes
Contacts
Principal investigator
Title
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A/Prof
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Name
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Marianne Phillips
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Address
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Clinic H, Room H14 Locked Bag 2010, Nedlands WA 6909
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Country
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Australia
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Phone
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+618 6456 4427
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Fax
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Email
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[email protected]
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Contact person for public queries
Title
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A/Prof
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Name
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Marianne Phillips
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Address
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Clinic H, Room H14 Locked Bag 2010, Nedlands WA 6909
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Country
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Australia
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Phone
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+618 6456 4427
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Title
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A/Prof
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Name
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Marianne Phillips
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Address
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Clinic H, Room H14 Locked Bag 2010, Nedlands WA 6909
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Country
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Australia
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Phone
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+618 6456 4427
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Fax
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Email
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[email protected]
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