Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03763422


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


Registration number
NCT03763422
Ethics application status
Date submitted
13/11/2018
Date registered
4/12/2018
Date last updated
1/02/2022

Titles & IDs
Public title
Trial in Low Grade Glioma Patients: Wait or Treat
Scientific title
IDH Mutated 1p/19q Intact Lower Grade Glioma Following Resection: Wait Or Treat? IWOT - a Phase III Study
Secondary ID [1] 0 0
EORTC-BTG-1635
Universal Trial Number (UTN)
Trial acronym
IWOT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low-grade Glioma 0 0
Temozolomide 0 0
Phase III 0 0
Wait or Treat 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Temozolomide
Treatment: Other - Radiotherapy
Treatment: Surgery - Surgery

Experimental: Early Treatment arm - Radiotherapy + Temozolomide

Active comparator: Active surveillance arm - Treatment as per local practice


Treatment: Drugs: Temozolomide
Oral Administration of Temozolomide

Treatment: Other: Radiotherapy
50.4 Gy in 28 fractions over 6 weeks

Treatment: Surgery: Surgery
Surgery
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Next intervention free survival (FIFS)
Timepoint [1] 0 0
From the date of randomization until initiation of second treatment or death whichever occurs first assessed up to 11.5 years as of first patient in (FPI)
Secondary outcome [1] 0 0
First intervention free survival (FIFS)
Timepoint [1] 0 0
from the date of randomization until initiation of preferably RT/TMZ or any other first therapeutic intervention (second surgery, RT, chemotherapy) or death (any cause) whichever occurs first assessed up to 11.5 years as of first patient in
Secondary outcome [2] 0 0
Progression Free Survival (PFS)
Timepoint [2] 0 0
From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first assessed up to 11.5 years as of first patient in
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
From the date of randomization up to the date of death up to 1 year after first progression or start of second treatment in early treatment arm or first treatment in active surveillance arm assessed up to 11.5 years as of first patient in
Secondary outcome [4] 0 0
Seizure activity
Timepoint [4] 0 0
The IWOT Seizure Control Composite Score Index can be completed up to 4 weeks before or after the planned assessment. A time window of 8 weeks is therefore available for each assessment. Assessed up to 11.5 years after FPI
Secondary outcome [5] 0 0
Safety profile: CTCAE
Timepoint [5] 0 0
The collection period will start from randomization and up to start of second treatment for patients in the early treatment arm and from randomization to first treatment, for patients in active surveillance arm. Assessed up to 11.5 years after FPI
Secondary outcome [6] 0 0
Translational research
Timepoint [6] 0 0
tissue and blood at randomization and new tissue at repeated surgical interventions if patient consented for translational research.Assessed up to 11.5 years after FPI
Secondary outcome [7] 0 0
HRQoL related to seizures
Timepoint [7] 0 0
From randomization until progression assessed up to 11.5 years as of FPI

Eligibility
Key inclusion criteria
* Histologically WHO grade II (diffuse) or III (anaplastic) astrocytoma, IDHmt without 1p/19q co-deletion (local diagnosis)
* Time since diagnostic surgery or first resection = 6 months
* No need for immediate radiotherapy followed by chemotherapy
* Having seizures only, without functional deficits due to the tumor (but the presence of functional deficits due to the resection is allowed)
* Patients for whom by local judgment an active surveillance policy is a realistic management alternative
* The patient is at least 18 years of age on day of signing informed consent
* WHO PS 0-2
* Adequate hematological, renal, and hepatic function, as follows:

* Absolute neutrophil count = 1.5 x 10*9/L
* Platelets = 100 × 10*9/L
* Serum creatinine = 1.5 times upper limit of laboratory normal (ULN)
* Total serum bilirubin = 1.5 × ULN
* AST and ALT = 2.5 × ULN
* Alkaline phosphatase of = 2.5 × ULN
* Presence of at least one paraffin block from the initial diagnosis for pathology review and translational research. If a representative formalin-fixed, paraffin-embedded (FFPE) block is not available, the collection of optimally 36, minimally 24 x 5 µm, unstained slides is required.
* At the time of randomization presence only of a non-enhancing tumor on T1 weighted contrast enhanced MR images; some faint non-nodular enhancement or enhancement that can be ascribed to the surgical resection or peri-operative ischemia is allowed. Preoperative enhancement is allowed provided this area is resected as shown on postoperative imaging
* Ability to take oral medication
* Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test done within 72 hours prior to randomization
* Patients of childbearing / reproductive potential must agree to use adequate birth control measures, as defined by the investigator, during RT and TMZ treatment and for at least 6 months after the last TMZ cycle. A highly effective method of birth control is defined as those which result in low failure rate (i.e., less than 1 percent per year) when used consistently and correctly
* Women who are breast feeding must agree to discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment
* Male patients should be advised not to father a child and not to donate sperm up to 6 months after receiving the last dose of TMZ, and to seek advice on cryoconservation of sperm prior to treatment start
* Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments
* Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Presence of signs of increased intracranial pressure after surgery
* Requirement of steroids for control of tumor symptoms
* Presence of uncontrolled seizures after surgery, defined as having both:

* persistent seizures interfering with everyday life activities AND
* failed three lines of anti-epileptic drug regimen, including at least one combination regimen
* Presence of contra-indications for radiotherapy
* Hypersensitivity to dacarbazine (DTIC), to the active substance or to any of the excipients used for TMZ capsules
* Prior chemotherapy, or prior radiotherapy to the brain
* Pregnancy or breastfeeding
* Known HIV, chronic hepatitis B, or hepatitis C infection
* Inability to take oral medication (e.g., frequent vomiting, partial bowel obstruction)
* Concurrent severe or uncontrolled medical disease (e.g., active systemic infection, diabetes, hypertension, coronary artery disease, 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 or prostate cancer (with PSA of less than or equal to 0.1 ng/mL). Other cancers for which the subject has completed potentially curative treatment more than 3 years prior to study entry are allowed
* 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
Treatment
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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/12/2021
Sample size
Target
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
Brisbane, QLDNSW,SA,TAS,VIC,West-Australi
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - University of Queensland - Woolloongabba
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Randwick - Sydney
Recruitment hospital [3] 0 0
Westmead Hospital - Crown Princess Mary Cancer Centre - Westmead
Recruitment hospital [4] 0 0
Illawarra Cancer Care Centre - Wollongong Hospital - Wollongong
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [7] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [8] 0 0
St Vincent's Hospital - Fitzroy (Melbourne)
Recruitment hospital [9] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [10] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
2031 - Randwick - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
2500 - Wollongong
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
7000 - Hobart
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3065 - Fitzroy (Melbourne)
Recruitment postcode(s) [9] 0 0
3084 - Heidelberg
Recruitment postcode(s) [10] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Vienna
Country [2] 0 0
Belgium
State/province [2] 0 0
Aalst
Country [3] 0 0
Belgium
State/province [3] 0 0
Wilrijk
Country [4] 0 0
Denmark
State/province [4] 0 0
Aarhus
Country [5] 0 0
France
State/province [5] 0 0
Bron
Country [6] 0 0
France
State/province [6] 0 0
Lille
Country [7] 0 0
France
State/province [7] 0 0
Marseille
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
France
State/province [9] 0 0
Strasbourg
Country [10] 0 0
Italy
State/province [10] 0 0
Bologna
Country [11] 0 0
Italy
State/province [11] 0 0
Firenze
Country [12] 0 0
Italy
State/province [12] 0 0
Meldola
Country [13] 0 0
Italy
State/province [13] 0 0
Milano
Country [14] 0 0
Italy
State/province [14] 0 0
Padova
Country [15] 0 0
Italy
State/province [15] 0 0
Torino
Country [16] 0 0
Netherlands
State/province [16] 0 0
Eindhoven
Country [17] 0 0
Netherlands
State/province [17] 0 0
Leiden
Country [18] 0 0
Netherlands
State/province [18] 0 0
Leidschendam
Country [19] 0 0
Netherlands
State/province [19] 0 0
Maastricht
Country [20] 0 0
Netherlands
State/province [20] 0 0
Rotterdam
Country [21] 0 0
Netherlands
State/province [21] 0 0
Tilburg
Country [22] 0 0
Netherlands
State/province [22] 0 0
Utrecht
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Valencia
Country [26] 0 0
Switzerland
State/province [26] 0 0
Bellinzona
Country [27] 0 0
Switzerland
State/province [27] 0 0
Lausanne
Country [28] 0 0
Switzerland
State/province [28] 0 0
Zürich
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Scotland
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Edinburgh
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Other
Name
European Organisation for Research and Treatment of Cancer - EORTC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cooperative Trials Group for Neuro-Oncology (COGNO)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Martin Van den Bent
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03763422

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Funding & Sponsors
Funding source category [1] 45
Government body
Name [1] 45
Cancer Australia
Address [1] 45
Level 14, 300 Elizabeth Street Sydney NSW 2000
Country [1] 45
Australia
Funding source category [2] 47
Charities/Societies/Foundations
Name [2] 47
Mark Hughes Foundation
Address [2] 47
PO Box 417 Hamilton NSW 2303
Country [2] 47
Australia
Primary sponsor
University
Primary sponsor name
The University of Sydney
Primary sponsor address
NHMRC Clinical Trials Centre,
University of Sydney
Lifehouse Level 6
119–143 Missenden Road,
Camperdown NSW 2050
Primary sponsor country
Australia
Other collaborator category [1] 44
Other Collaborative groups
Name [1] 44
Cooperative Trials Group for Neuro-Oncology (COGNO)
Address [1] 44
NHMRC Clinical Trials Centre Lifehouse Building, Level 6 119-143 Missenden Road Camperdown NSW 2050 Australia
Country [1] 44
Australia
Other collaborator category [2] 46
Other Collaborative groups
Name [2] 46
European Organisation for Research and Treatment for Cancer (EORTC)
Address [2] 46
Avenue E Mounierlaan 83/11 B-1200 Brussels Belgium
Country [2] 46
Belgium
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 22
SLHD Ethics Review Committee RPAH Zone
Address [1] 22
RPAH Medical Centre Suite 210A, 100 Carillon Avenue NEWTOWN NSW 2042
Country [1] 22
Australia
Date submitted for ethics approval [1] 22
25/01/2021
Approval date [1] 22
27/04/2021
Ethics approval number [1] 22
 
Public notes

Contacts
Principal investigator
Title 209 0
A/Prof
Name 209 0
Mark Pinkham
Address 209 0
Building 1 Ground Floor, Princess Alexandra Hospital 199 Ipswich Road Woolloongabba QLD 4102
Country 209 0
Australia
Phone 209 0
07 3176 7853
Fax 209 0
(07) 3176 1983
Email 209 0
[email protected]
Contact person for public queries
Title 210 0
Ms
Name 210 0
Trial Coordinator
Address 210 0
Level 6, Chris O'Brien Lifehouse 119-143 Missenden Road Camperdown NSW 1450
Country 210 0
Australia
Phone 210 0
(02) 9562 5000
Fax 210 0
(02) 9562 5094
Email 210 0
[email protected]
Contact person for scientific queries
Title 211 0
A/Prof
Name 211 0
Mark Pinkham
Address 211 0
Building 1 Ground Floor, Princess Alexandra Hospital 199 Ipswich Road Woolloongabba QLD 4102
Country 211 0
Australia
Phone 211 0
07 3176 7853
Fax 211 0
(07) 3176 1983
Email 211 0
[email protected]