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Trial in Low Grade Glioma Patients: Wait or Treat (IWOT)

E

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Terminated
Phase 3

Conditions

Wait or Treat
Low-grade Glioma
Temozolomide
Phase III

Treatments

Radiation: Radiotherapy
Procedure: Surgery
Drug: Temozolomide

Study type

Interventional

Funder types

NETWORK
Other

Identifiers

NCT03763422
EORTC-BTG-1635

Details and patient eligibility

About

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.

Enrollment

19 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

19 participants in 2 patient groups

Early Treatment arm
Experimental group
Description:
Radiotherapy + Temozolomide
Treatment:
Drug: Temozolomide
Radiation: Radiotherapy
Active surveillance arm
Active Comparator group
Description:
Treatment as per local practice
Treatment:
Drug: Temozolomide
Procedure: Surgery
Radiation: Radiotherapy

Trial contacts and locations

45

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Data sourced from clinicaltrials.gov

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