Molecular profiling-based assignment of cancer therapy (NCI-MPACT): A randomized multicenter phase II trial

Alice P. Chen, Shivaani Kummar, Nancy Moore, Lawrence V. Rubinstein, Yingdong Zhao, P. Mickey Williams, Alida Palmisano, David Sims, Geraldine O'Sullivan Coyne, Christina L. Rosenberger, Mel Simpson, Kanwal P.S. Raghav, Funda Meric-Bernstam, Stephen Leong, Saiama Waqar, Jared C. Foster, Mariam M. Konaté, Biswajit Das, Chris Karlovich, Chih Jian LihEric Polley, Richard Simon, Ming Chung Li, Richard Piekarz, James H. Doroshow

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


PURPOSE This trial assessed the utility of applying tumor DNA sequencing to treatment selection for patients with advanced, refractory cancer and somatic mutations in one of four signaling pathways by comparing the efficacy of four study regimens that were either matched to the patient's aberrant pathway (experimental arm) or not matched to that pathway (control arm). MATERIALS AND METHODS Adult patients with an actionable mutation of interest were randomly assigned 2:1 to receive either (1) a study regimen identified to target the aberrant pathway found in their tumor (veliparib with temozolomide or adavosertib with carboplatin [DNA repair pathway], everolimus [PI3K pathway], or trametinib [RAS/RAF/MEK pathway]), or (2) one of the same four regimens, but chosen from among those not targeting that pathway. RESULTS Among 49 patients treated in the experimental arm, the objective response rate was 2% (95% CI, 0% to 10.9%). One of 20 patients (5%) in the experimental trametinib cohort had a partial response. There were no responses in the other cohorts. Although patients and physicians were blinded to the sequencing and random assignment results, a higher pretreatment dropout rate was observed in the control arm (22%) compared with the experimental arm (6%; P =.038), suggesting that some patients may have had prior tumor mutation profiling performed that led to a lack of participation in the control arm. CONCLUSION Further investigation, better annotation of predictive biomarkers, and the development of more effective agents are necessary to inform treatment decisions in an era of precision cancer medicine. Increasing prevalence of tumor mutation profiling and preference for targeted therapy make it difficult to use a randomized phase II design to evaluate targeted therapy efficacy in an advanced disease setting.

Original languageEnglish
Pages (from-to)133-144
Number of pages12
JournalJCO Precision Oncology
Issue number5
StatePublished - Jan 2021


Dive into the research topics of 'Molecular profiling-based assignment of cancer therapy (NCI-MPACT): A randomized multicenter phase II trial'. Together they form a unique fingerprint.

Cite this