AMG 386 Drug-Drug Interaction Study With Paclitaxel

Eligible subjects enrolled in the study will begin receiving paclitaxel on a three weeks on / one week off schedule at study day 1 and weekly AMG 386 beginning at study day 8. The pharmacokinetic portion of the study occurs during the first two study cycles with intensive PK collections on study weeks 1, 6 and 8. Once the pharmacokinetic assessment period is completed, continued combination therapy with AMG 386 and paclitaxel or single-agent AMG 386 will be administered at the investigator's discretion until progression, unacceptable toxicity develops, or study withdrawal.

Inclusion criteria

• Men or women ≥ 18 years of age
• Have a pathologically documented, and definitely diagnosed, advanced solid tumor that is refractory to standard treatment, or for which no curative therapy is available
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Normal or clinically acceptable ECG (12 lead reporting PR, QRS, QTc)

Exclusion criteria

• Subjects with gastric cancer or any malignancy with purely squamous cell histology
• Known history of primary central nervous system (CNS) tumors or CNS metastases
• Myocardial infarction within 1 year before study day 1, unstable or uncontrolled disease/condition related to or affecting cardiac function
• History of stroke, arterial or venous thrombosis, or pulmonary embolism within 1 year before study day 1
• A baseline ECG QTc interval > 450 msec
• Active grade 2 or greater peripheral vascular disease
• History of pulmonary hemorrhage or gross hemoptysis within 6 months before study day 1
• Non-healing wound, ulcer (including gastrointestinal) or fracture
• Known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection
• Major surgery within 1 month before study day 1
• Concurrent antitumor treatment within 4 weeks (6 weeks for nitrosoureas or mitomycin) before study day 1
• Unable to tolerate IV administration or repeated blood withdrawal
• Hypersensitivity to paclitaxel or drugs using the vehicle cremophor
• Known sensitivity to mammalian-derived products, bacterially-produced proteins, or any of the products to be administered during dosing
• Chronic neuropathy grade ≥ 1
• Concurrent or prior treatment with 2C8 and 3A4 substrates
• Enrolled in or has not yet completed at least 30 days (prior to study day 1) since ending other investigational device or drug, or currently receiving other investigational treatment.
• Men and woman of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study and an additional 6 months after the last dose of AMG 386
• Women who are lactating/breastfeeding
• Women with a positive pregnancy test
• Women planning to become pregnant during the duration of the study