RecruitingPhase 3NCT03663725

Treatment Intensification With Temozolomide in Adults With a Glioblastoma

Phase III Randomised Trial Evaluating Treatment Intensification With Temozolomide in Adults With a Glioblastoma


Sponsor

Centre Oscar Lambret

Enrollment

486 participants

Start Date

Mar 13, 2019

Study Type

INTERVENTIONAL

Conditions

Summary

Due to conflicting data on the optimal moment to start TMZ chemotherapy and the impact of prolongation of the adjuvant phase with TMZ, the ANOCEF (Association des Neuro-Oncologues d'Expression Francophone) group proposes this randomized trial comparing an intensified arm (early TMZ and extended adjuvant TMZ until toxicity, progression or patient refusal) versus the classical EORTC regimen as control (RT and concomitant TMZ started 4-6 weeks after surgery followed by a number of adjuvant TMZ cycles strictly limited to 6) for primary GBM adult patients.


Eligibility

Min Age: 18 Years

Inclusion Criteria10

  • Patient ≥18 years old
  • Histological diagnosis of de novo GBM (extemporaneous diagnosis or standard pathological examination). In case of extemporaneous diagnosis, the patient can be included. If the diagnosis is not confirmed, the patient will be withdrawn from study.
  • Time between initial surgery/biopsy and planned start of treatment (if allocated to the experimental arm) ≤ 15 days (ideally in the first 7 days)
  • Karnofsky performance status (KPS) ≥ 60%, or KPS \<60% only related to glioma-related motor paresis.
  • Adequate biological functions
  • Common toxicity criteria (CTC) non hematological adverse events ≤ Grade 1 (except for alopecia, nausea, vomiting and neurological symptoms)
  • Females of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 6 months after stopping the study drug.
  • Standard radiation therapy deemed feasible (60 Gy, 30 fractions)
  • Time interval of less than 43 days between initial surgery/biopsy and planned start of radiation therapy
  • Written informed consent

Exclusion Criteria12

  • Secondary or recurrent glioblastoma (GBM)
  • Planned use of tumor-treating electric fields
  • Planned use of Carmustine implants
  • Prior malignancy in the last 5 years before inclusion or concomitant
  • Severe myelosuppression
  • Known hypersensitivity to any of the study drugs, study drug classes, excipients in the formulation or to dacarbazine (DTIC)
  • Current or recent treatment with another experimental drug or patients included in a clinical therapeutic trial (in the 30 days prior to inclusion).
  • Known current viral hepatitis, HIV infection or current active infectious disease
  • Inability to swallow oral medications or any mal-absorption condition
  • Pregnant or breastfeeding patients.
  • Inability to comply with medical follow-up of the trial (geographical, social or psychic reasons)
  • Person under guardianship or curatorship

Interventions

DRUGIntensified protocol

Early Temozolomide (TMZ) 1 cycle (150 mg/m²/ day X 5 days, per os) Started between day 2 and 15 after surgery/ biopsy RT (60 Gy, 2 Gy/fraction) + concomitant TMZ (75 mg/m2/day X 42 days, per os) Started between W4 and W6 after surgery/ biopsy Adjuvant TMZ 6 cycles (150-200 mg/m2 X 5 days /month, per os) Started 1 month after the end of the concomitant TMZ Prolonged TMZ Until progression, intolerance, patient's or physician's decision (150-200 mg/m2 every 4 weeks, per os)

DRUGStupp protocol

RT (60 Gy, 2 Gy/fraction) + concomitant Temozolomide (75 mg/m2/day X 42 days, per os) Started between W4 and W6 after surgery/ biopsy Adjuvant TMZ 6 cycles (150-200 mg/m2 X 5 days /month, per os) Started 1 month after the end of the concomitant TMZ


Locations(19)

Centre Léon Bérard

Lyon, France

CHU La Timone

Marseille, France

Centre Hospitalier d'Amiens

Amiens, France

ICO Centre Paul Papin

Angers, France

Centre François Baclesse

Caen, France

Centre Jean Perrin

Clermont-Ferrand, France

Hôpitaux Civils de Colmar

Colmar, France

Centre Georges François Leclerc

Dijon, France

CHU Grenoble Alpes

Grenoble, France

CHU de Limoges

Limoges, France

ICM Val d'Aurelle

Montpellier, France

CHRU Nancy

Nancy, France

ICO Centre René Gauducheau

Nantes, France

CHU de Nice - Hôpital de Cimiez

Nice, France

APHP La Pitié Salpêtrière

Paris, France

CH René Dubos

Pontoise, France

Institut Cancérologie Loire

Saint-Priest-en-Jarez, France

Centre Paul Strauss

Strasbourg, France

CHRU Tours

Tours, France

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NCT03663725


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