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Trial registered on ANZCTR


Registration number
ACTRN12609000485235
Ethics application status
Approved
Date submitted
8/01/2009
Date registered
18/06/2009
Date last updated
8/09/2024
Date data sharing statement initially provided
13/03/2020
Date results provided
15/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised phase III Trial on concurrent and adjuvant Temozolomide chemotherapy in non 1p/19q deleted anaplastic glioma to evaluate overall survival.
Scientific title
Phase III Trial on concurrent and adjuvant Temozolomide chemotherapy in non 1p/19q deleted anaplastic glioma to evaluate overall survival.
Secondary ID [1] 253293 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaplastic Glioma 4177 0
Condition category
Condition code
Neurological 4383 4383 0 0
Other neurological disorders
Cancer 4386 4386 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There will be 4 arms with the following interventions for treatments:

Arm 1- Radiotherapy only

Arm 2 - Radiotherapy and concomitant Temozolomide chemotherapy

Arm 3 - Radiotherapy and adjuvant Temozolomide chemotherapy

Arm 4 - Radiotherapy, concomitant Temozolomide chemotherapy and adjuvant Temozolomide chemotherapy.

Radiotherapy consists of a fractionated regimen delivering a total dose of 59.4 Gy in 6.5 weeks, in a once daily schedule of 1.8 Gy per fraction for a total of 33 fractions.

Concomitant Temozolomide - Patients randomised to this arm receive Temozolomide continuously orally at a daily dose of 75 mg/m2 1 hour before radiotherapy during weekdays. During weekends without radiotherapy, the drug will be taken in the morning. The dose administered will be determined by Body Surface Area (BSA), calculated at the beginning of the concomitant treatment. The daily dose throughout the trial will be rounded to the nearset 10 mg.

Adjuvant Temozolomide - Patients randomised to this arm will start adjuvant Temozolomide after a 4 week resting period after the end of radiotherapy. Temozolomide will then be administered orally once a day for 5 consecutive days (days 1-5). The starting dose of the first cycle will be 150 mg/m2/day with a single dose escalation to 200 mg/m2/day in subsequent cycles if no significant toxicity is observed in the first cycle. The dose administered will be determined using the Body Surface Area (BSA) calculated at the beginning of each treatment cycle.

Patients will receive a maximum of 12 cycles of Adjuvant Temozolomide.
Intervention code [1] 3896 0
Treatment: Drugs
Comparator / control treatment
Arm 1 Radiotherapy only
Control group
Active

Outcomes
Primary outcome [1] 5263 0
Overall survival
Timepoint [1] 5263 0
From the day of randomisation to death due to any cause. Patients would have three monthly disease and status assessment after the end of radiotherapy until death or when the last analysis is planned. Patients not reported dead or lost to follow up will be censored at the date of the last examination.
Secondary outcome [1] 8869 0
Progression free survival. From randomisation date to first date of disease progression or death, as assessed by Magnetic Resonance Imaging (MRI) or Computed Topography(CT) scans.
Timepoint [1] 8869 0
From randomisation date to first day of disease progression or death, as assessed by Magnetic Resonance Imaging (MRI) or Computed Topography (CT) scans. Patients will be assessed at baseline, 4 weeks after the end of radiotherapy and then three monthly till death. Time of final analysis will depend on finding status. Ideally, following all patients till death.
Secondary outcome [2] 8870 0
Neurological deterioration free survival.
1. Decrease in
World Health Organisation (WHO) performance status: For patients with baseline World Health Organisation (WHO) performance status 0: deterioration to World Health Organisation (WHO) performance status 2 or worse for which there is no other explanation, and which is maintained for at least 3 months. For patients with baseline World Health Organisation (WHO) performance status 1 or 2, deterioration to World Health Organisation (WHO) performance status 3 or worse for which there is no other explanation, and which is maintained for at least 3 months.
Timepoint [2] 8870 0
This outcome will be measured at baseline within 4 weeks of randomisation, during radiotherapy (weeks 4 and 6), 4 weeks after the end of radiotherapy, then every 3 months till death. If neither neurological deterioration nor death is observed, the patient in censored at the date of the last follow up.
Secondary outcome [3] 8871 0
Development of cognitive deterioration
Timepoint [3] 8871 0
Short cognitive screening with the Mini-Mental State Examination (MMSE) will take place at randomisation, 4 wks after radiotherapy and then at every scheduled 3 monthly follow-up visit till death. This 30 point test includes questions on orientation to time and place, registration, attention, calculations, recall, language and visual construction.
Secondary outcome [4] 8872 0
Toxicity as measured by Common Terminology Criteria for Adverse Events- Version 3(CTCAE v3).
Timepoint [4] 8872 0
Baseline

During Radiotherapy with or without concomitant chemotherapy - weekly, additional tests in weeks 4 and 6 and 4 wks after radiotherapy ends.

Patients are also tested every 3 months after ending radiotherapy.

Patients randomised to receive adjuvant temozolomide are followed every 4 weeks prior to start of the next cycle of temozolomide.

Maximum overall treatment time is 7 wks (theoretical treatment time is 6.5 weeks).

Any acute toxicity except the following: headache. fatigue, hair loss, skin reaction, sickness, mucositis (nasopharyx included), temporary reduced hearing (ear canal included) or temporary loss of taste (nasopharynx included), which are expected toxicities of cancer.
Secondary outcome [5] 8873 0
Quality of Life (QoL) will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire version 3 (QLQ-C30).
Timepoint [5] 8873 0
These will be completed within 14 days prior to randomisation, 4 weeks after radiotherapy, then at every 3 monthly visit. After discontinuation of treatment, every 3 months there will be a follow-up visit until death or 5 years, depending on which occurs earliest.

Eligibility
Key inclusion criteria
Histologically confirmed newly diagnosed anaplastic oligodendroglioma, anaplastic oligoastrocytoma or anaplastic astrocytoma by local diagnosis AND absence of combined 1p/19q loss. Both of which must have been determined by either local testing or central review.

Newly diagnosed disease

Prior surgery for a low grade tumour is allowed, provided histological confirmation of an anaplastic tumour is present at the time of progression.

Tumour material available for central 1p/19q assessment, central O6-methylguanine-DNAmethyltransferase promotor methylation status assessment and central pathology review.

Patients must be on a stable or decreasing dose of steroids for at lease 2 weeks prior to ransomisation.

WHO performance status 0-2

Start of radiotherapy within 8 days of randomisation

Start of radiotherapy within 7 weeks of (49 days) of surgery

No prior chemotherapy (including no treatment with Carmustine or bis-chloronitrosourea (BCNU) containing wafers (Gliadel)

No prior radiotherapy to the brain

No concomitant treatment with other anti-cancer agents or with any other experimental agent

Adequate renal, haematological and hepatic function according to all the following laboratory values (to be performed within 14 days prior to randomisation):
Neutrophils > or = 1.5*1000000000 cells/l
Platelets > or = 100*1000000000 cells/l
Bilirubin<1.5 times upper limit of laboratory normal

Alkaline phosphatase, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) < 2.5 times upperlimit for laboratory normal
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnant or breast feeding

Known Human Immunodeficiency Virus (HIV) infection, chronic hepatitis B or C infection.

Any medical condition that could interfere with follow-up, oral medication intake (eg. frequent vomiting, partial bowel obstruction)

Previous concurrent malignancies at other sites with the exemption of surgically cured carcinoma in situ of the cervix and non-melanoma skin cancer.

Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

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)
Central randomisation at site via computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients are centrally randomised by European Organisation for Research and Treatment of Cancer (EORTC) computer software using Dynamic (adaptive) random allocation methods such as Minimisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/09/2010
Actual
31/08/2010
Date of last participant enrolment
Anticipated
Actual
18/08/2015
Date of last data collection
Anticipated
30/06/2024
Actual
27/08/2024
Sample size
Target
748
Accrual to date
Final
751
Recruitment in Australia
Recruitment state(s)
TAS,NSW,VIC,QLD,SA,WA
Recruitment outside Australia
Country [1] 1516 0
Belgium
State/province [1] 1516 0
Country [2] 1517 0
United Kingdom
State/province [2] 1517 0
Country [3] 1518 0
United States of America
State/province [3] 1518 0
Country [4] 1519 0
Canada
State/province [4] 1519 0
Country [5] 1520 0
Belgium
State/province [5] 1520 0

Funding & Sponsors
Funding source category [1] 4358 0
University
Name [1] 4358 0
University of Sydney
Country [1] 4358 0
Australia
Funding source category [2] 288271 0
Other Collaborative groups
Name [2] 288271 0
Cancer Council Australia
Country [2] 288271 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
92 – 94 Parramatta Road, Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 3924 0
Other Collaborative groups
Name [1] 3924 0
European Organisation for Research and Trearment of Cancer (EORTC)
Address [1] 3924 0
EORTC Data Centre Avenue E.Mounier,laan,83/11 B-1200 Brussels
Country [1] 3924 0
Belgium
Secondary sponsor category [2] 3925 0
Other Collaborative groups
Name [2] 3925 0
Medical Research Council
Address [2] 3925 0
Medical Research Council
20 Park Crescent
London
W1B 1AL
Country [2] 3925 0
United Kingdom
Secondary sponsor category [3] 3926 0
Other Collaborative groups
Name [3] 3926 0
Radiation Therapy Oncology Group (RTOG)
Address [3] 3926 0
1818 Market Street,
Suite 1600
Philadelphia, PA 19103-3604
Country [3] 3926 0
United States of America
Other collaborator category [1] 281238 0
Other Collaborative groups
Name [1] 281238 0
Cooperative Trials Group for Neuro-Oncology (COGNO)
Address [1] 281238 0
NHMRC Clinical Trials Centre
Lifehouse Building, Level 6
119-143 Missenden Road
Camperdown
NSW 2050
Country [1] 281238 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6697 0
Cancer Institute NSW
Ethics committee address [1] 6697 0
Ethics committee country [1] 6697 0
Australia
Date submitted for ethics approval [1] 6697 0
Approval date [1] 6697 0
29/05/2009
Ethics approval number [1] 6697 0
AU RED Reference: HREC/09/CIC/3

Cancer Institute NSW Reference Number: 2009C/02/085
Ethics committee name [2] 293052 0
Sydney Local Health District Human Research Ethics Committee (RPA Zone)
Ethics committee address [2] 293052 0
Ethics committee country [2] 293052 0
Australia
Date submitted for ethics approval [2] 293052 0
Approval date [2] 293052 0
18/11/2013
Ethics approval number [2] 293052 0
HREC/13/RPA/492

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

Contacts
Principal investigator
Name 35075 0
Prof Anna Nowak
Address 35075 0
Comprehensive Cancer Centre, DD block, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands WA 6009.
Country 35075 0
Australia
Phone 35075 0
+61 8 6151 0897
Fax 35075 0
Email 35075 0
[email protected]
Contact person for public queries
Name 12422 0
CATNON Trial Coordinator
Address 12422 0
National Health and Medical Research Council (NHMRC) Clinical Trials Centre Locked Bag 77, Camperdown NSW 1450, Australia
Country 12422 0
Australia
Phone 12422 0
+61 295625000
Fax 12422 0
+61 2 95625094
Email 12422 0
[email protected]
Contact person for scientific queries
Name 3350 0
Anna Nowak
Address 3350 0
Comprehensive Cancer Centre, DD block, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands WA 6009.
Country 3350 0
Australia
Phone 3350 0
+61 8 6151 0897
Fax 3350 0
Email 3350 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
no information about it yet


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.