A Dose Escalation Study of MK-1775 in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001)

• Status: Completed
• Trial end date: 2014-01-06

Summary

This study will investigate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) activity of MK-1775, both as monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in participants with advanced solid tumors. Dose limiting toxicities (DLT) of MK-1775 in combination with gemcitabine, cisplatin, or carboplatin will also be assessed. The primary hypotheses of the study are as follows: 1) Oral administration of MK-1775 both as monotherapy and in combination with either gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors will be safe and tolerable, 2) The side effects observed in participants with advanced solid tumors after administration of MK-1775 combined with each of the chemotherapies (gemcitabine, cisplatin and carboplatin) will allow for the definition of a single dose combination Maximum Administered Dose (MAD)/Maximum Tolerated Dose (MTD) and a multiple dose combination Biologically Effective Dose (BED)/MTD for each of the 3 combinations, 3) At a tolerated dose, MK-1775 plasma exposure will exceed target thresholds established in preclinical models, and 4) At a tolerated dose, PD markers of MK-1775 activity in combination with either gemcitabine, cisplatin, or carboplatin (in surrogate tissue and/or tumor) will meet or exceed the target threshold established in preclinical models.

• Phase: Phase 1

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Adavosertib; Carboplatin; Cisplatin; Gemcitabine