Effect of Different Doses of AMG 706 on the Gallbladder in Advanced Solid Tumors

An Open-Label, Randomized, Phase 1b Study Evaluating the Effect of Different Doses of AMG 706 on the Gallbladder in Subjects With Advanced Solid Tumors

The study involves the use of three different dosing regimens of AMG 706 in patients with advanced solid tumors to see how the drug affects the gallbladder size and function. The study will be conducted in 11 sites in the US and Australia. A total of 48 patients will be enrolled in the study with the possibility of enrolling 8 more in each treatment arm.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: AMG 706; Drug: AMG 706; Drug: AMG 706

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed advanced metastatic solid tumor
• Ineligible to receive or progressed on standard of care therapies
• Measurable or non-measurable disease per modified RECIST
• Gallbladder must be in situ on screening ultrasound
• ECOG Performance Status of 0 to 2
• Life expectancy of 6 months or more as determined by the investigator
• Adequate organ and hematologic function as evidenced by laboratory studies prior to randomization
• Men and women 18 years or older

Exclusion Criteria:

• Uncontrolled CNS metastases
• Known history of prior cholecystitis, prior biliary procedure or prior or ongoing biliary disease
• Radiation therapy within 14 days prior to randomization
• Peripheral neuropathy > Grade 1 per CTC AE v.3
• Currently or previously treated with AMG 706 or other VEGF inhibitors such as SU11248 (sunitinib), PTK787 (vatalanib), AZD2171, BAY 43-9006 (sorafenib), ZD6474 (vandetanib)
• Previous treatment with bevacizumab is allowed if at least 6 weeks have elapsed from the last dose of bevacizumab to the date of randomization
• Any anti-coagulant therapy within 7 days prior to randomization; low dose heparin and warfarin for prophylaxis against central venous catheter thrombosis is allowed
• Less than 30 days have elapsed since participation in an investigational drug/device study or currently receiving investigational treatments
• History of arterial or venous thrombosis within 1 year prior to randomization
• History of bleeding diathesis or bleeding within 14 days of randomization
• MI, CVA, TIA, PTCA/stent, CHF, Grade 2 or greater PVD, uncontrolled arrhythmias or unstable angina within one year prior to randomization
• Uncontrolled HTN defined by a resting BP of >150/90 mmHg
• Surgery: major surgical procedure within 4 weeks or 28 days prior to randomization; minor surgical procedure, placement of access device or fine needle aspiration within 7 days of randomization; planned elective surgery while on study
• Non-healing or open wound, ulcer or fracture
• Known ongoing or active infection
• Known (+) for HIV, Hep C or Hep B surface antigen
• Known chronic hepatitis
• Known history of allergy or hypersensitivity to AMG 706 or any of its components
• Pregnant, ie, (+) b-HCG; breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm C; Arm C - AMG 706 75 mg BID 5-days on and 2-days off	Drug: AMG 706; Arm B - AMG 706 75 mg BID 2-weeks on and 1-week off; Drug: AMG 706; Arm C - 75 mg BID 5-days on, 2-days off; Drug: AMG 706; AMG 706 125 mg daily continuously (Arm A)
Other: Arm B; Arm B - AMG 706 75 mg BID 2-weeks on and 1-week off	Drug: AMG 706; Arm B - AMG 706 75 mg BID 2-weeks on and 1-week off; Drug: AMG 706; Arm C - 75 mg BID 5-days on, 2-days off; Drug: AMG 706; AMG 706 125 mg daily continuously (Arm A)
Other: Arm A; Arm A = AMG 706 125 mg PO daily continuously	Drug: AMG 706; Arm B - AMG 706 75 mg BID 2-weeks on and 1-week off; Drug: AMG 706; Arm C - 75 mg BID 5-days on, 2-days off; Drug: AMG 706; AMG 706 125 mg daily continuously (Arm A)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Average change from baseline in gallbladder size (volume by ultrasound)	Anticipated 8 months of treatment with AMG 706
Average change from baseline in gallbladder function (ejection fraction)	Subject treatment with AMG 706 anticipated to be 8 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Average changes from baseline in gallbladder size (volume by CT scan)	Subject treatment with AMG 706 anticipated to be 8 months
Maximum change from baseline in gallbladder size (volume) and function (ejection fraction)	Subject treatment with AMG 706 anticipated to be 8 months
Change in gallbladder size (volume) and function (ejection fraction) between the last on-treatment measurement and the last available off-treatment measurement	Subject treatment with AMG 706 anticipated to be 8 months
Objective response in subjects with measurable disease at baseline	Subject treatment with AMG 706 anticipated to be 8 months
Pharmacokinetics of AMG 706 monotherapy	Subject treatment with AMG 706 anticipated to be 8 months
Subject incidence of treatment-emergent adverse events (including all, serious, grade 3, grade 4 and treatment-related	Subject treatment with AMG 706 anticipated to be 8 months
Other selected gallbladder characteristics such as size, area, wall thickness, ductal size, presence of stones, pericholecystic fluid and sludge	Subject treatment with AMG 706 anticipated to be 8 months

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Rosen LS, Lipton L, Price TJ, Belman ND, Boccia RV, Hurwitz HI, Stephenson JJ Jr, Wirth LJ, McCoy S, Hei YJ, Hsu CP, Tebbutt NC. The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors. BMC Cancer. 2013 May 16;13:242. doi: 10.1186/1471-2407-13-242.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: March 15, 2007
• First Submitted That Met QC Criteria: March 15, 2007
• First Posted (Estimate): March 19, 2007

Study Record Updates

• Last Update Posted (Estimate): January 21, 2011
• Last Update Submitted That Met QC Criteria: January 20, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: solid tumors; Phase 1b; Amgen; gallbladder; AMG 706
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Micronutrients; Protein Kinase Inhibitors; Vitamins; Vitamin B Complex; Niacinamide; Imetelstat; Motesanib diphosphate
• Other Study ID Numbers: 20060443