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Randomized Controlled Trial
. 2018 Jun;144(6):1197-1204.
doi: 10.1007/s00432-018-2632-6. Epub 2018 Apr 11.

MODUL-a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach

Hans-Joachim Schmoll  1 , Dirk Arnold  2 , Aimery de Gramont  3 , Michel Ducreux  4 , Axel Grothey  5 , Peter J O'Dwyer  6 , Eric Van Cutsem  7 , Frank Hermann  8 , Ivan Bosanac  9 , Belguendouz Bendahmane  9 , Christoph Mancao  10 , Josep Tabernero  11
Affiliations
Randomized Controlled Trial

MODUL-a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach

Hans-Joachim Schmoll et al. J Cancer Res Clin Oncol. 2018 Jun.

Abstract

Purpose: The old approach of one therapeutic for all patients with mCRC is evolving with a need to target specific molecular aberrations or cell-signalling pathways. Molecular screening approaches and new biomarkers are required to fully characterize tumours, identify patients most likely to benefit, and predict treatment response.

Methods: MODUL is a signal-seeking trial with a design that is highly adaptable, permitting modification of different treatment cohorts and inclusion of further additional cohorts based on novel evidence on new compounds/combinations that emerge during the study.

Results: MODUL is ongoing and its adaptable nature permits timely and efficient recruitment of patients into the most appropriate cohort. Recruitment will take place over approximately 5 years in Europe, Asia, Africa, and South America. The design of MODUL with ongoing parallel/sequential treatment cohorts means that the overall size and duration of the trial can be modified/prolonged based on accumulation of new data.

Conclusions: The early success of the current trial suggests that the design may provide definitive leads in a patient-friendly and relatively economical trial structure. Along with other biomarker-driven trials that are currently underway, it is hoped that MODUL will contribute to the continuing evolution of clinical trial design and permit a more 'tailored' approach to the treatment of patients with mCRC.

Keywords: Biomarker; FOLFOX + bevacizumab; MODUL; Metastatic colorectal cancer; Signal seeking; Switch maintenance therapy.

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Conflict of interest statement

Ivan Bosanac, Belguendouz Bendahmane, and Christoph Mancao are employees of the study sponsor (F. Hoffmann-La Roche). All other authors report no relevant conflict of interest.

Figures

Fig. 1
Fig. 1
MODUL study design. FP fluoropyrimidine (5-FU/LV or capecitabine), 5-FU/LV 5-fluorouracil/leucovorin; MSI-H high microsatellite instability, MSS microsatellite stable. aPatients who progress early and who are not BRAFmut will enter the post-treatment follow-up phase with initiation of second-line treatment per Investigator discretion. bRandomization stratified by: Cohorts 1 and 2: region (EU, Americas, Africa, or Asia), induction treatment response (CR/PR vs. SD); Cohort 3: induction treatment response (CR/PR vs. SD), HER2 IHC (IHC0/ IHC1+/IHC2 + vs. IHC3+); Cohort 4: region (EU vs. rest of world), induction treatment response (CR/PR vs. SD), microsatellite stability (MSI-H vs. MSS), RAS status (wild-type KRAS and NRAS vs. mutant KRAS and/or NRAS). cPatients discontinuing study treatment for any reason during the induction or maintenance treatment phases will enter the post-treatment follow-up phase
Fig. 2
Fig. 2
Whole blood and plasma biomarker assessments
See this image and copyright information in PMC

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