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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: AMG 706
* Drug: AMG 706
* Drug: AMG 706


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gallbladder, AMG 706, solid tumors, Phase 1b, Amgen