Alliance for Clinical Trials in Oncology

The Alliance for Clinical Trials in Oncology is a National Cancer Institute-funded cooperative created in 2011 with the merger of the North Central Cancer Treatment Group (NCCTG), American College of Surgeons Oncology Group (ACOSOG) and the Cancer and Leukemia Group B (CALGB).  The Alliance is comprised of multiple multidisciplinary disease committees such as neuro-oncology, leukemia, breast and respiratory which coordinate clinical trials within their field.  Modality Committees (e.g. radiation oncology, oncology nursing) provide multidisciplinary support for each of the disease committees.  Scientific and operational support are provided by programs including Statistics and Data Management and Central Protocol Operations which interface with each disease committee as needed based on requirements of the clinical trials. The Tumor Section is represented at the Neuro-Oncology Committee and Neuro-radiology committee.

The Alliance meets regularly in Chicago, and the next meeting of the Neuro-Oncology Committee is Saturday, May 12, 2018.  The Alliance website can be found at:

www.allianceforclinicaltrialsinoncology.org

Currently open clinical trials supported by Alliance which are relevant to neuro-oncology are updated regularly on the Alliance website. 

One currently accruing trial with relevance to neurosurgeons is entitled “Corticosteroids + bevacizumab vs corticosteroids + placebo for radionecrosis after radiosurgery for brain metastases”. Also called the ‘BEST’ trial, the aim of this phase 2 study is to investigate whether adding bevacizumab to standard corticosteroid therapy leads to greater symptom improvement and less treatment-related side effects compared to steroids alone. Secondary objectives include evaluation of side effect profiles, quality of life assessments and comparison of intracranial PFS. Patients in the bevacizumab arm will receive 10 mg/kg IV on days 1 and 15 of a 28 day cycle for 4 cycles. Target enrollment is 130 patients and the PI is Caroline Chung, MD at MD Anderson.

A number of trials are currently in development through the Alliance and do not appear on the website or clinicaltrials.gov. One example is a recurrent GBM trial in development entitled “A phase 2 study of Anti-PD-1/PD-L1 blockade immunotherapy in patients with hypermutated recurrent glioblastoma.” In the current study design, patients with first or second recurrence of their glioblastoma are eligible. Surgery is performed to confirm recurrence and provide specimen for Foundation Medicine panel. Patients with greater than 20 mutations are sub-classified as hypermutated and randomized 1:1 to receive either durvalumab or clinician’s choice standard of care. Patients considered non-hypermutated are randomized 1:1 to receive either durvalumab plus tremelimumab or clinician’s choice standard of care. The PI for this study is Gavin Dunn.

Neurosurgeons interested in further information regarding the Alliance are encouraged to contact Brad Elder, MD (brad.elder@osumc.edu) to discuss possible opportunities for involvement.

Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma

A newly-opened clinical trial NCT03180268:  NRG-BN003, a Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma

Daniel Cahill, MD, PhD and Michael Vogelbaum, MD, PhD

The NRG Oncology cooperative group is one of two National Cancer Institute (NCI)-funded cancer clinical cooperative groups with a special focus on clinical trials for brain cancers.  As a historical reminder, in 2014 the three legacy groups (consisting of the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG)) were unified into the combined group now known as “NRG Oncology”.

Important for the Tumor Section, we highlight a new study that holds special importance for neurosurgeons, NRG-BN003. This trial is for patients with World Health Organization (WHO) grade II (atypical) meningiomas that have received gross-total resection (GTR), which is built upon results from the prior study RTOG-0539 from the legacy RTOG group.  Initial results of this study, presented at the 2015 ASTRO meeting by Rogers et al, noted that a subset of the pre-determined intermediate risk group of patients consisted of grade II atypical meningiomas that had undergone GTR (n=36); of these patients, after receipt of intensity modulated radiation therapy (IMRT), only 1 patients had died from disease progression at the 3 year timepoint. Thus, the investigators concluded that postoperative RT was a supported treatment option for GTR WHO grade II meningiomas, due to the documented minimal toxicity from IMRT and high rates of tumor control.

With this study as background, this NRG Oncology trial, led by Dr. Leland Rogers, aims to accrue 148 patients to determine whether IMRT after GTR of a WHO grade II meningioma improves progression-free survival when compared to observation, as measured from randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed up to 10 years. GTR (Simpson Grade 1-3) must be confirmed on post-operative imaging following the most recent surgery; submission of both pre-operative and post-operative MRIs is required for patients. In this phase III study, patients are then randomized to 1 of 2 arms after undergoing GTR. In ARM 1, patients undergo observation. In ARM 2, patients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions (59.4 Gy in 33 daily fractions of 1.8 Gy each).  After completion of study treatment, patients are followed up at 3, 6, and 12 months, every 6 months for year 2 and 3, then yearly for 10 years. Important exclusion criteria include optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma, or definitive evidence of metastatic meningioma.

Neurosurgeons are anticipated to be the critical drivers of patient enrollment in this trial, through the identification of patients who can meet enrollment criteria.  

Other Clinical Trials

For a full list of recent neuro-oncology clinical trials, please see the clinicaltrials.gov website.