Trial in Low Grade Glioma Patients: Wait or Treat

NCT03763422 | Terminated Phase 3 DMC

• 1 other identifier: EORTC-BTG-1635
• Study Type: interventional
• Target: 19
• Locations: 9 countries
• Sites: 35

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• Next intervention free survival (FIFS)

  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)

  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)

  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

  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

  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

  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

Study Arms (2)

Early Treatment arm

EXPERIMENTAL

Radiotherapy + Temozolomide

Drug: Temozolomide; Radiation: Radiotherapy

Active surveillance arm

ACTIVE COMPARATOR

Treatment as per local practice

Drug: Temozolomide; Radiation: Radiotherapy; Procedure: Surgery

Interventions

Temozolomide DRUG

Oral Administration of Temozolomide

Also known as: TMZ

Active surveillance arm; Early Treatment arm

Radiotherapy RADIATION

50.4 Gy in 28 fractions over 6 weeks

Also known as: RT

Active surveillance arm; Early Treatment arm

Surgery PROCEDURE

Surgery

Active surveillance arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Cooperative Trials Group for Neuro-Oncology (COGNO): collaborator

Study Sites (45)

Princess Alexandra Hospital - University of Queensland

Woolloongabba, Brisbane, QLD, 4102, Australia

Location

Prince of Wales Hospital

Randwick - Sydney, New South Wales, 2031, Australia

Location

Westmead Hospital - Crown Princess Mary Cancer Centre

Westmead, New South Wales, 2145, Australia

Location

Illawarra Cancer Care Centre - Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital

Fitzroy (Melbourne), Victoria, 3065, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Universitaetskliniken der Uni Wien - Universitaetsklinikum Wien - AKH uniklinieken

Vienna, 1090, Austria

Location

Onze Lieve Vrouw Ziekenhuis

Aalst, 9300, Belgium

Location

Gasthuiszusters van Antwerpen - GasthuisZusters Antwerpen - Sint-Augustinus

Wilrijk, 2610, Belgium

Location

Aarhus University Hospitals - Aarhus University Hospital-Skejby

Aarhus, 8250, Denmark

Location

CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer

Bron, 69677, France

Location

CHRU de Lille

Lille, 59037, France

Location

Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone (APHM)

Marseille, 13385, France

Location

Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere

Paris, 75651, France

Location

Institut de Cancerologie Strasbourg Europe (formar Paul Strauss)

Strasbourg, 67200, France

Location

AUSL Bologna - Ospedale Bellaria

Bologna, 40139, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Istituto Clinico Humanitas

Milan, 20089, Italy

Location

IRCCS - Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

IRCCS - Istituto Oncologico Veneto

Padua, 35128, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale San Giovanni - Dipartimento Neuroscienze

Torino, 10126, Italy

Location

Catharina Ziekenhuis

Eindhoven, 5602, Netherlands

Location

Leiden University Medical Centre

Leiden, 2300, Netherlands

Location

Haaglanden Medisch Centrum (HMC) - Haaglanden MC - locatie Antoniushove

Leidschendam, BA 2262, Netherlands

Location

Maastro Clinic - Maastricht Radiation Oncology

Maastricht, 6229, Netherlands

Location

Erasmus MC

Rotterdam, 2040, Netherlands

Location

ETZ Tilburg - St. Elisabethziekenhuis TweeSteden

Tilburg, 5022, Netherlands

Location

UMC-Academisch Ziekenhuis Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital Clinic Universitari de Barcelona

Barcelona, 08036, Spain

Location

Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Institut Catala d'Oncologia - Hospital Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

Oncology Institute of Southern Switzerland (IOSI)

Bellinzona, 6500, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

UniversitaetsSpital Zurich

Zurich, 8091, Switzerland

Location

NHS Tayside - Ninewells Hospital

Dundee, Scotland, DD1 9SY, United Kingdom

Location

NHS Lothian - Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Clatterbridge Centre for Oncology NHS Trust - Clatterbridge NHS -Wirral

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

MeSH Terms

Interventions

Temozolomide; Radiotherapy; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Martin Van den Bent

  EORTC Study Coordinator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: December 4, 2018
• Study Start: March 16, 2020
• Primary Completion: December 29, 2021
• Study Completion: December 29, 2021
• Last Updated: February 1, 2022

Record last verified: 2022-01

Locations

CH (3); ES (6); BE (2); DK (1); AU (1); IT (7); GB (3); FR (5); NL (7)