Trial in Low Grade Glioma Patients: Wait or Treat

NCT ID: NCT03763422

Last Updated: 2022-02-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-16
• Study Completion Date: 2021-12-29

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early Treatment arm

Radiotherapy + Temozolomide

Group Type: EXPERIMENTAL

Temozolomide

Intervention Type: DRUG

Oral Administration of Temozolomide

Radiotherapy

Intervention Type: RADIATION

50.4 Gy in 28 fractions over 6 weeks

Active surveillance arm

Treatment as per local practice

Group Type: ACTIVE_COMPARATOR

Temozolomide

Intervention Type: DRUG

Oral Administration of Temozolomide

Radiotherapy

Intervention Type: RADIATION

50.4 Gy in 28 fractions over 6 weeks

Surgery

Intervention Type: PROCEDURE

Surgery

Interventions

Temozolomide

Oral Administration of Temozolomide

Intervention Type: DRUG

Radiotherapy

50.4 Gy in 28 fractions over 6 weeks

Intervention Type: RADIATION

Surgery

Surgery

Intervention Type: PROCEDURE

Other Intervention Names

TMZ; RT

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cooperative Trials Group for Neuro-Oncology (COGNO)

UNKNOWN

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin Van den Bent

Role: PRINCIPAL_INVESTIGATOR

EORTC Study Coordinator

Locations

Princess Alexandra Hospital - University of Queensland

Woolloongabba, Brisbane, QLD, Australia

Prince of Wales Hospital

Randwick - Sydney, New South Wales, Australia

Westmead Hospital - Crown Princess Mary Cancer Centre

Westmead, New South Wales, Australia

Illawarra Cancer Care Centre - Wollongong Hospital

Wollongong, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Monash Medical Centre

Clayton, Victoria, Australia

St Vincent's Hospital

Fitzroy (Melbourne), Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Universitaetskliniken der Uni Wien - Universitaetsklinikum Wien - AKH uniklinieken

Vienna, , Austria

Onze Lieve Vrouw Ziekenhuis

Aalst, , Belgium

Gasthuiszusters van Antwerpen - GasthuisZusters Antwerpen - Sint-Augustinus

Wilrijk, , Belgium

Aarhus University Hospitals - Aarhus University Hospital-Skejby

Aarhus, , Denmark

CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer

Bron, , France

CHRU de Lille

Lille, , France

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

Marseille, , France

Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere

Paris, , France

Institut de Cancerologie Strasbourg Europe (formar Paul Strauss)

Strasbourg, , France

AUSL Bologna - Ospedale Bellaria

Bologna, , Italy

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Istituto Clinico Humanitas

Milan, , Italy

IRCCS - Istituto Neurologico Carlo Besta

Milan, , Italy

IRCCS - Istituto Oncologico Veneto

Padua, , Italy

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

Torino, , Italy

Catharina Ziekenhuis

Eindhoven, , Netherlands

Leiden University Medical Centre

Leiden, , Netherlands

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

Leidschendam, , Netherlands

Maastro Clinic - Maastricht Radiation Oncology

Maastricht, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

ETZ Tilburg - St. Elisabethziekenhuis TweeSteden

Tilburg, , Netherlands

UMC-Academisch Ziekenhuis Utrecht

Utrecht, , Netherlands

Hospital Clinic Universitari de Barcelona

Barcelona, , Spain

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

Barcelona, , Spain

Institut Catala d'Oncologia - Hospital Germans Trias i Pujol

Barcelona, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario 12 De Octubre

Madrid, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Oncology Institute of Southern Switzerland (IOSI)

Bellinzona, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

UniversitaetsSpital Zurich

Zurich, , Switzerland

NHS Tayside - Ninewells Hospital

Dundee, Scotland, United Kingdom

NHS Lothian - Western General Hospital

Edinburgh, , United Kingdom

Clatterbridge Centre for Oncology NHS Trust - Clatterbridge NHS -Wirral

Metropolitan Borough of Wirral, , United Kingdom

Countries

Australia; Austria; Belgium; Denmark; France; Italy; Netherlands; Spain; Switzerland; United Kingdom

Other Identifiers

EORTC-BTG-1635

Identifier Type: -

Identifier Source: org_study_id