Gateway for Cancer Research funds EORTC 1634-BTG trial in post-pubertal brain tumor patients

Gateway for Cancer Research℠ awards grant to the EORTC 1634- Brain Tumour Group (BTG) academic trial in Post-Pubertal Patients with Newly-Diagnosed Medulloblastoma (PersoMed-I).

Medulloblastoma is a rare brain tumor. In the US, it affects 550 adults, and in Europe around 450 adults annually, with the majority being young adults. Adolescent and adult medulloblastomas are biologically distinct in comparison to pediatric medulloblastomas, which mandates age adapted treatment strategies. Adolescent patients all bear an intermediate to high prognostic risk, leading to poor patient survival and disability. We are still unaware of the most effective treatment with the lowest possible rate of side effects (long-term toxicity) for this age group.

Today, treatment consists of maximal surgical removal plus craniospinal radiotherapy and maintenance chemotherapy. Treatment toxicity is high and often includes decline of cognition, fertility, neurological function and hearing, connected to severe impairments of quality of life, social and professional function. There is therefore an unmet medical and scientific need to help treat adolescent and adult patients burdened by this rare brain tumour.

The EORTC 1634-BTG trial and connected translational research projects provide a unique opportunity to investigate a personalized medical therapy that can be applied to about 70% of adolescent and adult patients with medulloblastoma, all the while addressing highly relevant toxicity and efficacy aspects in this highly under-investigated population, with an eminent output for affected patients in view of increasing survival rates and patient re-integration socially and professionally, alike.

Gateway for Cancer Research awarded over $500K to the EORTC-1634BTG study, marking the first collaboration between the two organisations. "EORTC is proud to count Gateway for Cancer Research as their partner in tackling unmet patient-centred needs in cancer clinical research. Their support contributes to an important international randomised clinical trial that will pave new avenues in neuro-oncology for adolescent and adult patients", commented Dr. Denis Lacombe, EORTC CEO.

"Gateway for Cancer Research and EORTC are deeply committed to advancing research that ultimately changes the standard of care for cancer patients worldwide," said Michael Burton, president and CEO, Gateway for Cancer Research. "We are proud to partner with EORTC to fund this promising clinical trial, and we are confident that our collaboration will truly accelerate progress for the patients we are privileged to serve."

The study

The EORTC1634-BTG PersoMed I study is a European based study (50 sites in 9 countries) with an intergroup collaboration in Australia. It will be the first prospective randomized trial in post-pubertal and adult patients with medulloblastoma. In view of novel combination therapies, it will use a targeted therapy in combination with radio-chemotherapy in a randomized setting, based on evaluation of the genetic subtype of medulloblastoma, and will therefore be personalized. The study will prospectively investigate molecular subtypes in an adult population, addressing the area of better characterization of cancers through biomarkers, and will implement a dose reduction of radio-chemotherapy in its experimental arms, focusing on treatment de-escalation. It will unify the pediatric and the adult neuro-oncology trial world and be the first trial worldwide that includes pediatric and adult patients in a prospective setting, also addressing patient feedback.

The primary objective of EORTC 1634-BTG is to compare PFS (progression free survival) of a personalized intensity-modulated therapy (experimental arm; sonidegib) vs. standard therapy (modified NOA-07) in the Sonic Hedgehog (SHH)-dependent subgroup. It therefore aims to improve PFS, translating into a higher survival rate and clinically relevant functional improvements for the affected patients.

In addition, by decreasing toxicity in its risk-adapted setting, the study will help to decrease short- and long-term toxicity burden and thereby help to re-integrate affected patients in their social and professional lives. The study also implements effective interventions that enable symptom management during and after treatment and empower patients to better handle their disease and become actively involved in their care decisions. This is reflected in tight toxicity management plans, patient education and monitoring of patient-reported outcomes.

Secondary objectives include additional efficacy objectives as well as toxicity of treatment. As patient reported outcomes are highly important in a setting where young patients in the middle of their lives are affected, short- and long-term health-related quality of life (HR-QoL), neurocognitive function, social outcome and endocrine function will be assessed in the study.

A total of 205 patients will be recruited over a period of 3 years. Patient follow-up duration until primary objective, after LPI (last patient in), is estimated at 4.6 year to provide the targeted number of events for the study analysis. The overall duration of this study is 9 years and is coordinated by Professor Peter Hau (Universitaetsklinikum Regensburg, Germany).

On the study's importance, Professor Peter Hau commented: "The EORTC 1634-BTG trial is the first randomised trial in adults with medulloblastoma worldwide. It both aims to decrease treatment toxicity and increase efficacy in targeted subpopulations of patients with medulloblastoma and will thereby be the first randomised trial ever in medulloblastoma that uses a targeted therapy. In addition to its immediate output, it will also generate a wealth of clinical, imaging and biological data that will help to develop the field further after the trial has concluded."