A Dose Escalation Study of Adavosertib (MK-1775) in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001)
Summary
This study will investigate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) activity of adavosertib, both as monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in participants with advanced solid tumors. Dose limiting toxicities (DLT) of adavosertib in combination with gemcitabine, cisplatin, or carboplatin will also be assessed. The primary hypotheses of the study are as follows: 1) Oral administration of adavosertib 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 adavosertib 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, adavosertib plasma exposure will exceed target thresholds established in preclinical models, and 4) At a tolerated dose, PD markers of adavosertib 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.
Timeline
- Start
- 2008-02-25
- Primary completion
- 2014-01-06
- Completion
- 2014-01-06
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Adavosertib | Small molecule | 25 mg | Oral |
| Subject | Adavosertib | Small molecule | 50 mg | Oral |
| Subject | Adavosertib | Small molecule | 75 mg | Oral |
| Subject | Adavosertib | Small molecule | 100 mg | Oral |
| Subject | Adavosertib | Small molecule | 125 mg | Oral |
| Subject | Adavosertib | Small molecule | 150 mg | Oral |
| Subject | Adavosertib | Small molecule | 175 mg | Oral |
| Subject | Adavosertib | Small molecule | 200 mg | Oral |
| Subject | Adavosertib | Small molecule | 225 mg | Oral |
| Subject | Adavosertib | Small molecule | 250 mg | Oral |
| Subject | Adavosertib | Small molecule | 325 mg | Oral |
| Subject | Adavosertib | Small molecule | 650 mg | Oral |
| Subject | Adavosertib | Small molecule | 1300 mg | Oral |
| Subject | Carboplatin | Small molecule | 5 unknown | Intravenous |
| Subject | Cisplatin | Other / unclassified | 75 mg/m2 | Intravenous |
| Subject | Gemcitabine | Small molecule | 1000 mg/m2 | Intravenous |