Table 1.

Summary of recommendations for neuro-oncology clinical trial eligibility

Criterion	Types of Trials	Recommendation
Age	Primary brain tumor	• Allow children (age ≥12) to participate in adult trials when disease biology and clinical course is similar in children and adults • Allow older patients (age ≥65) to participate on trials, particularly in diseases such as GBM where older patients represent a significant portion of the patient population
Functional status	Solid tumor phase I trials	• Performance score requirement can be of ECOG ≤2 or equivalent KPS of ≥60 for selected phase 1 clinical trial based on mechanism of action and expected toxicity profile.
Comorbid medical conditions	Primary brain tumor	• Allow participation of patients with a prior or concurrent history of malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, rather than specifying a specific time frame since completion of treatment
	Immunotherapy	• Allow patients with select, well-controlled autoimmune diseases to enroll on immune checkpoint inhibitor trials, eg, thyroiditis
Concomitant medications	Immunotherapy	• Allow corticosteroids at baseline but consider limiting maximum total daily doses of 2 mg dexamethasone and/or stratification according to dexamethasone dose in randomized trials
Long washout	Primary brain tumor	• Use 5 half-lives rather than a 4-week washout from prior therapy with short half-life. A general statement that the patient must have recovered from the effects of prior treatment would allow for even broader participation, particularly when prior therapy has long half-life.
Archival tissue requirements	Primary brain tumor	• The amount of tissue required for study enrollment needs a strong rationale and should be limited to what is necessary
Molecular subtypes	Primary brain tumor	• For molecular targets that are not stable throughout the disease course, a repeat biopsy should be considered to confirm target expression
Laboratory values	Primary brain tumor	• Only the relevant laboratory tests based on the safety profile of the study agent should be used as the basis for eligibility criteria • For those laboratory tests included as eligibility criteria, allow for a safe range above normal parameters
	Immunotherapy	• Depending on the trial design and primary outcome, baseline ALC > 1000 cells/µL is ideal, but ≥500 cells/µL may be reasonable
Pathology	GBM	• Patients with tumors meeting criteria for “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV” should be allowed to participate on GBM clinical trials • Patients with IDH-mutant GBM can be included in phase 0/I GBM studies where efficacy is not primary endpoint or patients can be stratified by IDH status in randomized studies
	Solid tumor phase I trials	• Patients with primary brain tumors including lower-grade gliomas and other rare CNS tumors should be included in dose escalation phases of solid phase I clinical trials • Exploratory expansion cohorts of specific brain tumor histopathology should be included if there is a biologic rationale for efficacy
Prior therapy	Phase I	• Allow inclusion regardless of prior therapy unless a particular study question makes the prior therapy relevant • Allow prior exposure to bevacizumab
	Phase II/III recurrent GBM	• When efficacy is an important endpoint and there is a high likelihood that outcomes may be influenced by prior therapies, strategies to allow broader enrollment include specifying separate analyses for patients who have or have not received the particular treatment (eg, bevacizumab refractory vs bevacizumab naïve), enrolling separate arms for these patient populations, or stratifying randomization based on prior exposure.
Number of relapses	Recurrent GBM and phase I	• Allow any number of prior relapses, especially in phase 0/I trials and especially in bevacizumab- naïve patients
	Recurrent GBM and phase II	• Allow at least 2 prior relapses in bevacizumab-naïve patients