Neoplasms

All Conditions

Nervous System Diseases

Behaviors and Mental Disorders

Rare Diseases

Glioma

Brain Neoplasms

Oligodendroglioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Quality of Life

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Vincristine

Lomustine

Procarbazine

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Radiotherapy (RT) for over approximately 5-6 weeks:

* at 50.4/54 Gy in 1.8 Gy fractions for grade II and
* at 59.4 Gy in 1.8 Gy fractions for grade III gliomas

PCV cycles are 6 weeks long and given as:

* Day 1: Lomustine (CCNU) at 110 mg/m2 body surface orally,
* Days 8/29: Vincristine 1.4 mg/m2 i.v. (capped at 2 mg),
* Days 8-21: Procarbazine 60 mg/m2 orally (capped at 100 mg).

Six 42-day cycles of lomustine plus temozolomide according to the commonly used regimen:

* Day 1: Lomustine (CCNU) at 100 mg/m2
* Days 2-6: Temozolomide at 100 mg/m2 (cycles 1) and in 50 mg/m2 steps to 200 mg/m2 from cycle 2 on dependent on hematological toxicity

At progression, patients without prior radiotherapy will undergo radiotherapy and PCV as an adjunct chemotherapy if bone marrow reserve allows in the experimental arm.

CETEG

In the comparator arm there is the option for second radiotherapy or even reuse of the full radiochemotherapy regimen as it had been given at diagnosis (BIC).

Radiotherapy at 50.4/54 Gy in 1.8 Gy fractions for grade II and 59.4 Gy in 1.8 Gy fractions for grade III gliomas

Wolfgang Wick, Prof. Dr.

Antje Wick, PD Dr.

Oligodendrogliomas in the novel edition of the Central Nervous System (CNS) World Health Organization (WHO) classification are now molecularly defined by isocitrate dehydrogenase (IDH)1 or IDH2 mutations and 1p/19q co-deletion. The prognosis of these molecularly defined tumors is to be determined in new series since survival data from older histology-based studies and population-based registries are confounded by the inclusion of 20-70% not molecularly matching subsets. Also, the optimal treatment is a matter of ongoing investigations. An extensive, but safe surgery is associated with improved outcome as is the addition of chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) to the partial brain radiotherapy (RT). However, the exact timing of postsurgical therapy especially for tumors of the WHO grade II and acknowledging some variability in grading as well as the choice of chemotherapy, temozolomide instead of PCV (CODEL: NCT00887146 randomizing CNS WHO grade 2 and 3 oligodendrogliomas to chemoradiation(CHRT)therapy with PCV or with temozolomide) or the need for primary radiotherapy RT are subjects of clinical studies (POLCA: NCT02444000 randomizing patients with newly diagnosed CNS WHO grade 3 oligodendrogliomas to standard CHRT with PCV or PCV alone). Given the young age of patients with CNS WHO grade 2 and 3 oligodendrogliomas and the relevant risk of neurocognitive, functional and quality-of-life impairment with the current aggressive standard of care treatment, chemoradiation with PCV, of the tumor located in the brain optimizing care is the major challenge.

NOA-18/IMPROVE CODEL aims at improving qualified overall survival (qOS) for adult patients with CNS WHO grade 2 and 3 oligodendrogliomas by randomizing between standard chemoradiation with up to six six-weekly cycles with PCV and six six-weekly cycles with lomustine and temozolomide (CETEG), thereby delaying radiotherapy (RT) and adding the chemoradiotherapy (CHRT) concept at progression after initial radiation-free chemotherapy, allowing for an effective salvage treatment and delaying potentially deleterious side effects. QOS represents a new concept and is defined as OS without functional and/or cognitive and/or quality of life (QOL) deterioration regardless whether tumor progression or toxicity is the main cause.

The primary objective of the NOA-18/IMPROVE CODEL trail is to show superiority of an initial CETEG treatment followed by partial brain radiotherapy (RT) plus PCV (RT-PCV) at progression over partial brain radiotherapy (RT) followed by procarbazine, lomustine and vincristine (PCV) chemotherapy (RT-PCV) and best investigators choice (BIC) at progression for sustained qOS. An event with respect to a sustained qOS is then defined as a functional and/or cognitive deterioration on two consecutive study visits with an interval of 3 months, tolerating a deviation of at most 1 month. Assessments are done with 3-monthly MRI, assessment of the NANO (Neurologic assessment in neuro-oncology) scale, HRQoL, and KPS (Karnofsky performance status) and annually cognitive testing. Secondary objectives are evaluation and comparison of the two groups regarding secondary endpoints (short-term qOS, PFS, OS, complete and partial response rate). The trial is planned to be conducted at 21 NOA (Neurooncology Working Party of the German Cancer Society) study sites in Germany.

A Clinical Study to Improve Brain Function and Quality of Life of Patients With Newly Diagnosed Brain Tumors (Gliomas).

Improvement of Functional Outcome for Patients With Newly Diagnosed Grade II or III Glioma With Co-deletion of 1p/19q - IMPROVE CODEL: the NOA-18 Trial

The primary efficacy endpoint is the overall survival without functional and/or cognitive and/or quality of life deterioration over a period of 90 days, coined qualified overall survival (qOS). Short-term qOS is defined as the time from randomization to a deterioration in any of the following measures: NeuroCogFX®, KPI, HRQoL, NANO scale or death.

A decline is a reduction in the mean percentile rank in 2 or more items (Fliessbach et al.

2010, Hoffermann et al. 2017) in two or more subset scores of established neuropsychometric test batteries determined by NeuroCogFX® (Fliessbach et al. 2010).

A decrease in the KPI from 100 or 90 to 70 or less, a decrease in KPI of at least 20 from 80 or less, or a decrease in KPS from any baseline to 50 or less.

Fulfilment of one of these criteria is considered neurological deterioration unless attributable to comorbid events or changes in corticosteroid dose (van den Bent et al.

2011).

A worsening of at least 10 points, which is the minimal clinically relevant difference, in at least one of the five selected domains of the HrQoL (global health status (GHS), physical functioning (PF), social functioning (SF), determined in the QLQ-C30 with higher scores indicate better HRQoL; communication deficits (CD) \& motor dysfunction (MD) determined by QLQ-BN20 with lower scores indicate better HRQoL) (Taphoorn et al. 2015).

A decline in the NANO scale defined as a ≥2 level worsening from baseline within ≥1 domain or worsening to the highest score within ≥1 domain that is felt to be related to underlying tumor progression and not attributable to a comorbid event or change in concurrent medication (Nayak et al. 2017).

Defined as qOS as described above (deterioration in NeuroCogFX®, KPI, HRQoL, NANO scale or death) but neglecting the subsequent time interval of 3 months (90 days).

Defined as the time from randomization until death due to any cause.

Defined as the time from randomization to the day of first documentation of clinical or radiographic tumor progression or death of any cause.

Spots Global Cancer Trial Database for ceteg

Every month we try and update this database with for ceteg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ceteg

Every month we try and update this database with for ceteg cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ceteg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.