Correlation of single arm versus randomised phase 2 oncology trial characteristics with phase 3 outcome.
OBJECTIVE
The primary aim of this study was to determine whether randomised phase 2 (RP2) trials predict phase 3 trial outcome better than single arm phase 2 (SAP2) studies. Although theoretical superiority of RP2 trials has been postulated, no empiric studies have been conducted.


METHODS
Published phase 3 trials testing systemic cancer therapy were identified through a Medline search. Those of superiority design, which cited phase 2 trials supporting the experimental arm, were included. Trial design and outcome details were extracted. Statistical analysis was performed using the Generalized Estimating Equation method correlating phase 2 features with phase 3 outcome, accounting for any phase 3 duplication.


RESULTS
Of 189 eligible phase 3 trials, 18.5% were in haematological malignancies and 81.5% in solid tumors. The primary outcome was positive in 79 (41.8%). These were supported by 336 phase 2 trials (range 1-9 per phase 3 trial) including 66 RP2 trials. Positive phase 2 outcome, randomised or not, correlated with positive phase 3 outcome (p=0.03). RP2 studies were not superior to SAP2 studies at predicting phase 3 study success. Phase 2 trial features not predictive of phase 3 outcome included primary endpoint, sponsorship, sample size, similarity in patient population and therapy.


CONCLUSIONS
RP2 studies were not superior to SAP2 trials at predicting phase 3 study success. Further research into phase 2 trial design is required given the added resources required to conduct RP2 studies and the lack of empiric evidence supporting superiority over single arm studies.
Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, Canada. Electronic address: jose.monzon@albertahealthservices.ca.
Jose G
JG
Monzon
NCIC Clinical Trials Group, Queen's University, Kingston, Canada.
Annette E
AE
Hay
NCIC Clinical Trials Group, Queen's University, Kingston, Canada.
Gail T
GT
McDonald
NCIC Clinical Trials Group, Queen's University, Kingston, Canada.
Joseph L
JL
Pater
Department of Oncology, Juravinski Hospital and Cancer Centre and McMaster University, 711 Concession St., Hamilton, Ontario L8V 1C3, Canada.
Ralph M
RM
Meyer
Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
Eric
E
Chen
NCIC Clinical Trials Group, Queen's University, Kingston, Canada.
Bingshu E
BE
Chen
NCIC Clinical Trials Group, Queen's University, Kingston, Canada.
Janet E
JE
Dancey
D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000592:standards*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods / Q000592:standards*; D018572:Disease-Free Survival; D004358:Drug Therapy / Q000379:methods / Q000592:standards; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000592:standards*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards*; D012074:Remission Induction; D012107:Research Design / Q000592:standards; D018401:Sample Size
Clinical trials; Phase 2; Randomised; Single-arm