Background: Cbz is approved for treatment of pts with hormone-refractory metastatic prostate cancer after progression on a docetaxel-containing regimen. The dose-escalation part of this Phase I study (NCT00925743) found the maximum tolerated dose (MTD) of Cbz/Cis to be 15/75 mg/m². No Cbz–Cis PK interactions were seen. As Cbz is mainly metabolized by CYP3A, the study also evaluated the impact of a strong CYP3A inhibitor (K; study part 3) or strong CYP3A inducer (R; study part 4) on the PK of Cbz in combination with Cis. Methods: The study included pts with metastatic or unresectable solid tumors for which Cis-based therapy was considered appropriate. Pts received Cbz/Cis every 3 weeks at MTD, with K 400 mg (part 3) or R 600 mg (part 4) administered orally once daily prior to, on, and after Cycle 2 Day 1 for a total of 10 (K) or 14 (R) days. In part 3, the Cbz/Cis dose was 5/75 mg/m² in Cycles 1 and 2 to provide a safety margin to the MTD. Effects on Cbz PK were assessed with a linear mixed-effects model. The primary endpoint was Cbz clearance (CL). Safety assessments included adverse events (AEs) and laboratory abnormalities. Results: The PK population included 23 pts (part 3) and 21 pts (part 4). Repeated administration of K resulted in a 20% decrease in Cbz CL (L/h/m²) (geometric mean ratio [GMR]: 0.80; 90% confidence interval [CI]: 0.55, 1.15; n = 18), corresponding to a 25% increase in AUC (ng*h/mL/mg/m²) (GMR: 1.25; 90% CI: 0.86, 1.81; n = 18). Repeated administration of R resulted in a 21% increase in Cbz CL (L/h/m²) (GMR: 1.21; 90% CI: 0.95, 1.53; n = 20), corresponding to a 17% decrease in AUC (ng*h/mL/mg/m²) (GMR: 0.83; 90% CI: 0.65, 1.05; n = 20). The GMR of AUC_0–24was 1.09 (90% CI: 0.9, 1.33; n = 21), suggesting a low impact of R during the initial phases of Cbz elimination. The most frequent AEs included nausea (part 3: 68%; part 4: 74%), vomiting (part 3: 68%; part 4: 74%) and fatigue (part 3: 52%; part 4: 70%). Conclusions: The CL of Cbz was decreased by 20% by co-administration with K and increased by 21% by co-administration with R. Safety results were consistent with prior findings for this Cbz/Cis combination. Clinical trial information: NCT00925743.