Table 1.

Summary of RRCTs

	ALT-TRACC	EX-TEM	REAL-Pro
Primary objective	To examine the feasibility of a multi-centre prospective RRCT evaluating alternating oxaliplatin and irinotecan doublet schedules versus continuous clinician choice doublet chemotherapy during initial treatment of metastatic colorectal cancer	To determine the overall survival impact of an additional six cycles of post-radiation temozolomide following the current standard of concurrent chemoradiation and six cycles of temozolomide	To compare the incidence of cognitive decline in elderly patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate versus enzalutamide
Study design	Phase II open-label, multi-centre, registry-based randomised controlled trial	Phase III open-label, multi-centre, registry-based randomised controlled trial	Phase IIII Prospective, open-label, multi-centre, registry-based randomised clinical trial
Population	Patients diagnosed with treatment-naïve metastatic colorectal cancer (mCRC) deemed by their treating clinician to be fit for doublet chemotherapy	Newly diagnosed patients with histologically confirmed glioblastoma (WHO grade IV) and radiologically stable or responding disease (as per RANO criteria) following concurrent chemoradiation and six cycles of post-radiation temozolomide	Men aged 75 years or older with mCRPC appropriate for treatment with enzalutamide or abiraterone acetate
Randomisation and treatment arms	Patients randomised in a 1:1 ratio to one of two treatment arms: alternating cycles of oxaliplatin and then irinotecan doublet chemotherapy (experimental arm) versus continuous doublet chemotherapy (control arm).	Patients randomised in a 1:1 ratio after completing concurrent chemoradiation and six cycles of post-radiation temozolomide: observation (control arm) versus six further cycles (experimental arm) of post radiation temozolomide chemotherapy.	Participants stratified according to previous docetaxel treatment (yes/no) and randomised in a 1:1 ratio to enzalutamide versus abiraterone acetate
Primary endpoint	Progression free survival	Overall survival	Cognitive function
Secondary endpoints	Efficacy and toxicity by collecting data from the TRACC registry	Progression free survival, adverse events and the necessity for temozolomide dose modification to be determined by data entered into the BRAIN registry	Depression, falls and serious adverse events determined by data recorded in the ePAD registry

ALT-TRACC Alternating oxaliplatin and irinotecan doublets versus continuous doublet chemotherapy in previously untreated metastatic colorectal cancer, EX-TEM Phase III Trial of Extended Temozolomide in Newly Diagnosed Glioblastoma, REAL-Pro Registry-based Study of Enzalutamide vs Abiraterone assessing cognitive function in Elderly Metastatic Castration-Resistant Prostate Cancer