Low-grade GliomaPhase 3IWOTNCT03763422
Trial in Low Grade Glioma Patients: Wait or Treat
A Phase 3 study testing Temozolomide, Radiotherapy and Surgery in people with Low-grade Glioma and Temozolomide, run by European Organisation for Research and Treatment of Cancer - EORTC at 45 sites in 10 countries.
Trial summary
The 1635-EORTC-BTG study - Wait or Treat - concerns patients that represent a clinically favorable group of patients with IDHmutated astrocytoma (oligo-symptomatic), without a need for immediate post-operative treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Low-grade Glioma, Temozolomide, Phase III
- What is being tested?
- Temozolomide, Radiotherapy and Surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 45 sitesin 10 countries
- Study dates
- 16 Mar 2020to 29 Dec 2021
- Phase
- Phase 3
- 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
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
45 sites in 10 countries.
45 sites in 10 countries
Australia10 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Monash Medical Centre
Clayton, Victoria, 3168
St Vincent's Hospital
Fitzroy (Melbourne), Victoria, 3065
Austin Hospital
Heidelberg, Victoria, 3084
Royal Hobart Hospital
Hobart, Tasmania, 7000
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
Prince of Wales Hospital
Randwick - Sydney, New South Wales, 2031
Westmead Hospital - Crown Princess Mary Cancer Centre
Westmead, New South Wales, 2145
Illawarra Cancer Care Centre - Wollongong Hospital
Wollongong, New South Wales, 2500
Princess Alexandra Hospital - University of Queensland
Woolloongabba, Brisbane, QLD, 4102
Italy7 sites
AUSL Bologna - Ospedale Bellaria
Bologna, 40139
Azienda Ospedaliero-Universitaria Careggi
Florence, 50134
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014
Istituto Clinico Humanitas
Milan, 20089
IRCCS - Istituto Neurologico Carlo Besta
Milan, 20133
IRCCS - Istituto Oncologico Veneto
Padova, 35128
Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale San Giovanni - Dipartimento Neuroscienze
Torino, 10126
Netherlands7 sites
Catharina Ziekenhuis
Eindhoven, 5602
Leiden University Medical Centre
Leiden, 2300
Haaglanden Medisch Centrum (HMC) - Haaglanden MC - locatie Antoniushove
Leidschendam, BA 2262
Maastro Clinic - Maastricht Radiation Oncology
Maastricht, 6229
Erasmus MC
Rotterdam, 2040
ETZ Tilburg - St. Elisabethziekenhuis TweeSteden
Tilburg, 5022
UMC-Academisch Ziekenhuis Utrecht
Utrecht, 3584 CX
Spain6 sites
Hospital Clinic Universitari de Barcelona
Barcelona, 08036
Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals
Barcelona, 08908
Institut Catala d'Oncologia - Hospital Germans Trias i Pujol
Barcelona, 08916
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario 12 De Octubre
Madrid, 28041
Hospital Universitario La Fe
Valencia, 46026
France5 sites
CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
Bron, 69677
CHRU de Lille
Lille, 59037
Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone (APHM)
Marseille, 13385
Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
Paris, 75651
Institut de Cancerologie Strasbourg Europe (formar Paul Strauss)
Strasbourg, 67200
Switzerland3 sites
Oncology Institute of Southern Switzerland (IOSI)
Bellinzona, 6500
Centre Hospitalier Universitaire Vaudois
Lausanne, 1011
UniversitaetsSpital Zurich
Zurich, 8091
United Kingdom3 sites
NHS Tayside - Ninewells Hospital
Dundee, Scotland, DD1 9SY
NHS Lothian - Western General Hospital
Edinburgh, EH4 2XU
Clatterbridge Centre for Oncology NHS Trust - Clatterbridge NHS -Wirral
Metropolitan Borough of Wirral, CH63 4JY
Belgium2 sites
Onze Lieve Vrouw Ziekenhuis
Aalst, 9300
Gasthuiszusters van Antwerpen - GasthuisZusters Antwerpen - Sint-Augustinus
Wilrijk, 2610
Austria1 site
Universitaetskliniken der Uni Wien - Universitaetsklinikum Wien - AKH uniklinieken
Vienna, 1090
Denmark1 site
Aarhus University Hospitals - Aarhus University Hospital-Skejby
Aarhus, 8250
About this study
Official title: IDH Mutated 1p/19q Intact Lower Grade Glioma Following Resection: Wait Or Treat? IWOT - a Phase III Study
The 1635-EORTC-BTG study - Wait or Treat - concerns patients that represent a clinically favorable group of patients with IDHmutated astrocytoma (oligo-symptomatic), without a need for immediate post-operative treatment. It will establish whether early adjuvant treatment with radiotherapy and adjuvant temozolomide in resected IDHmutated astrocytoma will improve outcome, and whether benefits of early treatment outweigh potential side-effects of that, such as deterioration in neurocognitive function or Quality of Live, seizure activity and Patient Reported outcome compared to active surveillance.
- Conditions
- Low-grade Glioma, Temozolomide, Phase III, Wait or Treat
- Being tested
- Temozolomide, Radiotherapy, Surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called TMZ
Oral Administration of Temozolomide
RadiotherapyRadiation
Also called RT
50.4 Gy in 28 fractions over 6 weeks
SurgeryProcedure or surgery
Surgery
| Study group | Role | What they receive |
|---|---|---|
| Early Treatment arm | Experimental | Radiotherapy + Temozolomide Receives: Drug: Temozolomide; Radiation: Radiotherapy |
| Active surveillance arm | Active comparator | Treatment as per local practice Receives: Drug: Temozolomide; Radiation: Radiotherapy; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Next intervention free survival (FIFS)
Measured: 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 outcomes (7)
First intervention free survival (FIFS)
Measured: 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
Progression Free Survival (PFS)
Measured: 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
Overall Survival
Measured: 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
Seizure activity
Seizure activity will be evaluated by the IWOT Seizure Control Composite Score Index completed by patients with an additional answer from the local investigator.
Measured: 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
Safety profile: CTCAE
This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, for adverse event reporting.
Hematological toxicity will be assessed on the basis of blood counts. The nadir count will be assessed for each cycle of TMZ therapy, and graded according to CTCAE.
Non-hematological acute side effects will be assessed and reported separately for each cycle of TMZ therapy, and graded according to the Common Terminology Criteria for Adverse Events version 5.0.
Measured: 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
Translational research
The main objectives of TR are the assessment of markers that can identify patients in whom an active surveillance policy is not recommended or who are at risk to develop delayed complications is important. Furthermore, identification of predictive factors that could guide when to start RT and chemotherapy would aid the implementation of an active surveillance approach in clinical practice.
Measured: 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
HRQoL related to seizures
A seizure specific questionnaire will be used. The Seizure Control Composite Score Index is self-reported 7-item questionnaire developed to assess seizures frequency and severity.
Measured: From randomization until progression assessed up to 11.5 years as of FPI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2018
- Study start16 Mar 2020
- Primary completion29 Dec 2021
- Study completion29 Dec 2021
Why it stopped: Poorly recruiting
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Low-grade GliomaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Cooperative Trials Group for Neuro-Oncology (COGNO)
- Responsible party
- Sponsor
- Investigators
- Martin Van den Bent, Principal investigator, EORTC Study Coordinator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03763422
- Sponsor's protocol ID
- EORTC-BTG-1635
- Acronym
- IWOT
- Status last verified
- Jan 2022
- First submitted
- 13 Nov 2018
- Last updated
- 1 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IDH Mutated 1p/19q Intact Lower Grade Glioma Following Resection: Wait Or Treat? IWOT - a Phase III Study
- ClinicalTrials.gov ID
- NCT03763422
- Acronym / sponsor ID
- IWOT / EORTC-BTG-1635
- Conditions
- Low-grade Glioma, Temozolomide, Phase III, Wait or Treat
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poorly recruiting
- Enrolment
- 19 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Collaborators
- Cooperative Trials Group for Neuro-Oncology (COGNO)
- Study start
- 16 Mar 2020 (actual)
- Primary completion
- 29 Dec 2021 (actual)
- Study completion
- 29 Dec 2021 (actual)
- First posted
- 4 Dec 2018 (actual)
- 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.
The 1635-EORTC-BTG study - Wait or Treat - concerns patients that represent a clinically favorable group of patients with IDHmutated astrocytoma (oligo-symptomatic), without a need for immediate post-operative treatment. It will establish whether early adjuvant treatment with radiotherapy and adjuvant temozolomide in resected IDHmutated astrocytoma will improve outcome, and whether benefits of early treatment outweigh potential side-effects of that, such as deterioration in neurocognitive function or Quality of Live, seizure activity and Patient Reported outcome compared to active surveillance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early Treatment arm | Experimental | Drug: Temozolomide, Radiation: RadiotherapyRadiotherapy + Temozolomide |
| Active surveillance arm | Active comparator | Drug: Temozolomide, Radiation: Radiotherapy, Procedure: SurgeryTreatment as per local practice |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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
Key exclusion criteria (14 listed)
- 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:
- Presence of contra-indications for radiotherapy
- Hypersensitivity to dacarbazine (DTIC), to the active substance or to any of the excipients used for TMZ 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 |
|---|---|---|
| TemozolomideAlso: TMZOral Administration of Temozolomide | Drug | Active surveillance arm, Early Treatment arm |
| RadiotherapyAlso: RT50.4 Gy in 28 fractions over 6 weeks | Radiation | Active surveillance arm, Early Treatment arm |
| SurgerySurgery | Procedure or surgery | Active surveillance arm |
Primary outcome
Next intervention free survival (FIFS)
Time frame: 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)
7 secondary outcomes
First intervention free survival (FIFS)
Time frame: 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
Progression Free Survival (PFS)
Time frame: 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
Overall Survival
Time frame: 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
Seizure activity
Time frame: 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
Safety profile: CTCAE
Time frame: 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
Translational research
Time frame: 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
HRQoL related to seizures
Time frame: From randomization until progression assessed up to 11.5 years as of FPI
Results and safety
The study was stopped early (reason given: Poorly recruiting). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2022.
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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.
Martin Van den Bent principal investigator
EORTC Study Coordinator
45 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Temozolomide, Radiotherapy and Surgery in people with Low-grade Glioma and Temozolomide, run by European Organisation for Research and Treatment of Cancer - EORTC at 45 sites in 10 countries.
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 23 inclusion and 14 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 1 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in Australia, Italy, Netherlands, Spain, France and 5 more countries. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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: Poorly recruiting). 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?
Next intervention free survival (FIFS) (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Feb 2022; AzTrials last refreshed its copy on 26 Oct 2026.