Table 3 Selected published trials of oncology drugs in healthy volunteers sorted by study objective
From: Reviewing the role of healthy volunteer studies in drug development
NCT number, PMID number | Treatment | Target/MOA | Study population/study design | Study objective/study endpoints | Enrolled (N) |
|---|---|---|---|---|---|
Mass balance | |||||
 NCT01674322, 25488930 [47] | [14C]-Ibrutinib | Bruton tyrosine kinase | Single center, open-label, single-dose study in healthy males | PK of total radioactivity, parent drug and metabolites (plasma, urine, feces) based on CYP2D6 genotype | 6 (2 CYP2D6 poor metabolizer subjects) |
 NCT01711762, 26451002 [46] | [14C]-Cobimetinib | MEK inhibitor | Single center, open-label, nonrandomized study in healthy males | PK of total radioactivity, parent drug and metabolites (plasma, urine, feces) | 6 |
Bioequivalence | |||||
 N/A, 26272586 [52] | Ceritinib | ALK inhibitor | Two randomized, open-label, 2-period, crossover studies in healthy subjects | Changes in bioavailability with low- or high-fat meal, or light snack compared to fasting conditions | 40 (28, 12) |
 N/A, 25643050 [53] | Erlotinib | EGFR inhibitor | Two single center, open-label, crossover studies (two and three sequence) in healthy subjects | Changes in bioavailability when coadministered with ranitidine or omeprazole | 48 (24 each) |
 N/A, 28776077 [57] | Abiraterone Acetate | CYP17 inhibitor | Single center, open-label, fixed treatment sequence, 3-period, single-dose, crossover study in healthy males | Changes in bioavailability with novel formulation under both fasted and fed conditions compared with historical controls | 11 |
Biosimilarity | |||||
 NCT01603264, 25041377 [80] | Trastuzumab (PF-05280014, EU-, or US-approved trastuzumab) | HER2 inhibitor | Single center, double-blind, parallel group, single-dose, 3-arm, active comparator trial in healthy subjects | Establish 3-way clinical PK similarity of PF-05280014 to both EU- and US-trastuzumab formulations, and of EU- to US-trastuzumab | 101 |
 NCT01608087, 28651442 [59] | Bevacizumab, (BI 695502, US-, or EU-approved bevacizumab) | VEGF inhibitor | Two center, randomized, single-blind, single-dose, two-stage, 3 parallel-arm, active-comparator trial in healthy subjects | Establish 3-way clinical PK similarity to enable use of just one reference product for a Phase III biosimilarity trial | 91 |
Drug–drug interaction | |||||
 NCT01147055, NCT01149785, 26381275 [81] | Crizotinib | ALK inhibitor | Two single center, open-label, 2-period, 2-treatment, 1-sequence, single-dose, crossover studies in healthy subjects | Estimate the effects of multiple doses of ketoconazole and rifampin on single-dose PK | 30 (15 each) |
 N/A, 20702754 [66] | Nilotinib | BCR/ABL inhibitor | Two single center, open-label, 2-period, 1 sequence, single-dose crossover studies in healthy subjects | Estimate the effects of multiple doses of ketoconazole and rifampin on single-dose PK | 15 (rifampin) 26 (ketoconazole) |
Organ impairment | |||||
 NCT01298063, 24906422 [68] | Afatinib | EGFR inhibitor | Single center, open-label, single-dose study comparing mild (n = 8) and moderate hepatic impairment (n = 8) to matched healthy controls (n = 16) | Compare relative drug exposure between subjects with hepatic impairment and matched healthy controls, as measured by AUC0−∞ and Cmax | 32 |
 NCT02096718, 27436099 [69] | Single center, open-label, single-dose study comparing moderate (n = 8) and severe renal impairment (n = 8) to matched healthy controls (n = 14) | Compare relative drug exposure between subjects with renal impairment and matched healthy controls, as measured by AUClast and Cmax | 30 | ||
Pharmacokinetic/pharmacodynamic relationships | |||||
 N/A, 28660498 [70] | Degarelix | GnRH antagonist | Single center, double-blind (open-label for moxifloxacin) randomized, crossover study in healthy males | Compare the effect of single-dose degarelix, placebo, and moxifloxacin on the QT interval | 80 |
 NCT00406406, 22884766 [64] | Bosutinib | Src/Abl inhibitor | Single-center, randomized, double-blind, placebo-controlled, single-ascending dose, sequential-group study in healthy subjects | Assess the safety, tolerability, and PK with ascending doses to support further clinical pharmacology assessment | 48 |
 N/A, 20376000 [73] | Sunitinib | PDGFR/VEGFR/KIT/FLT3/CSF1R/RET inhibitor | Single center, open-label, multiple dose study in healthy subjects | To develop a PD/PK model to investigate the concentration-effect relationship between drug and biomarkers (blood pressure, VEGF-A, VEGF-C and sVEGFR-2) | 12 |