Page 54 - Read Online
P. 54

Farlow et al. J Cancer Metastasis Treat 2019;5:18  I  http://dx.doi.org/10.20517/2394-4722.2018.100                          Page 7 of 10

               Table 3. Ongoing window trials in head and neck squamous cell carcinoma
                                  Principal
                Type            investigator/    Agent(s)              Inclusion criteria*         NCT
                                 institution
                Targeted therapy  Duvurri/University of   AZD6738, olaparib  Newly diagnosed, treatment naive  03022409
                             Pittsburgh                    Planned surgery/biopsy + adjuvant RT and/or chemo
                Immunotherapy  Wolf/University of   IRX-2  Stage II-IVA OCSCC                    02609386
                             Michigan                      Treatment naive
                                                           KPS ≥ 70%
                                                           Adequate hematologic, hepatic, and renal function
                Immunotherapy  Worden/University of  Pembrolizumab  Any T stage with ≥ N2 disease  02641093
                             Michigan                      T4 disease, any N stage
                                                           T3 OCSCC, any N stage
                                                           Clinical evidence of ECE
                                                           ECOG 0-1
                Immunotherapy  Neskey/Medical   Nivolumab  Newly diagnosed, treatment naive, T2-T4, M0 OCSCC; or  03021993
                             University of South           Recurrent/persistent locoregional T2-T4 OCSCC initially
                             Carolina                      treated with surgery alone, ECOG 0-1
                Immunotherapy  Schoenfeld/Dana-  Nivolumab ±   ≥ T2 ± ≥ N1 surgically resectable OCSCC  02919683
                             Farber Cancer Institute Ipilimumab  ECOG 0-1
                                                           Adequate hematologic, hepatic, and renal function
                Immunotherapy  Porosnicu/Wake Forest Durvalumab  Surgically resectable OCSCC/OPSCC  02827838
                                                           No prior immunotherapy or RT
                                                           ECOG 0-1
                                                           Adequate hematologic, hepatic, and renal function
                Immunotherapy  Curry/Thomas   Durvalumab ±   Surgically resectable HNSCC         03618654
                             Jefferson       Metformin     ECOG 0-1
                                                           Body weight > 30 kg
                                                           Adequate hematologic, hepatic, and renal function
                Targeted therapy/  Ferris/University of   Motolimod and   Treatment naive Stage II-IVA HNSCC  02124850
                immunotherapy  Pittsburgh    Cetuximab ±   Planned surgical resection
                                             Nivolumab     ECOG 0-1
                                                           Adequate hematologic, hepatic, and renal function
               *Inclusion criteria abbreviated. See ClinicalTrials.gov for full inclusion and exclusion criteria, as well as primary endpoints for each trial.
               HNSCC: head and neck squamous cell carcinoma; NCT: ClinicalTrials.gov identifier; OCSCC: oral cavity SCC; OPSCC: oropharyngeal SCC;
               P: pharynx; HP: hypopharynx; L: larynx; KPS: Karnofsky performance status; ECOG: Eastern Cooperative Oncology Group Performance
               Scale; RT: radiotherapy; ECE: extracapsular extension

               the studied agents, although work remains to duplicate and understand these results.


               By definition, window trials occur in a short timeframe, which requires careful coordination to obtain
               the desired imaging studies, tumor tissue, and serial biologic samples. As the authors of a recent study
               discuss [15,31] , this can be difficult in a patient population that often has socioeconomic and adherence
               challenges with an already complicated diagnosis and treatment strategy to discuss. For this reason and
               because patients may be hesitant to take an investigational drug that should not be marketed to improve
               clinical outcomes in the research setting, accrual can take longer than expected. Accrual goals were not
               uniformly available for the studies included in this review, and many unpublished planned window trials
               may have failed due to poor accrual. Narrowing subject selection to specific tumor sites (i.e., oral cavity,
               oropharynx, larynx, or hypopharynx) or immunogenomic profiles may further elongate recruitment
               timelines.

               Pre- and post-treatment tissue is readily available by nature of the window of opportunity design, but the
               timing, selection, processing, and analysis protocols for tumor tissue and other desired body fluid samples
               must be considered. Tumor heterogeneity is a well-known phenomenon, and immunogenomic profiles
               can vary across both space and time. Pharmacokinetics of the drug under study should also be factored
               into the timing of obtaining biologic samples. Unlike in breast cancer where Ki67 is commonly employed,
               HNSCC studies have not coalesced on particular biomarkers, nor do standardized protocols for obtaining
               biomarker data or evaluating their clinical impact exist as of yet [14,15] . Several window trials discussed
               here were not randomized or did not use data from control subjects, which has been known to complicate
   49   50   51   52   53   54   55   56   57   58   59