Clinical trial NCT01992341: AMG 386 Drug-Drug Interaction Study With Paclitaxel
Official title: An Open-Label, Pharmacokinetic Drug-Drug Interaction (DDI) Study of AMG 386 in Combination With Paclitaxel in Adult Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: sarcomas
carcinomas
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the pharmacokinetics of paclitaxel when given alone and in combination with AMG 386 to determine whether AMG 386 alters the pharmacokinetics of paclitaxel

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Paclitaxel PK parameters
timeFrame: 9 weeks
Secondary outcomes:
measure: AMG 386 PK parameters
timeFrame: 9 weeks
measure: Safety
timeFrame: Average of 6 months
measure: Safety
timeFrame: Average of 6 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: