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

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT00448786

Collaborator

(none)

Enrollment

Arms

24.9

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: AMG 706 Drug: AMG 706 Drug: AMG 706	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

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

Arm

Intervention/Treatment

Other: Arm C

Arm C - AMG 706 75 mg BID 5-days on and 2-days off

Drug: AMG 706

Arm C - 75 mg BID 5-days on, 2-days off

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

Other: Arm A

Arm A = AMG 706 125 mg PO daily continuously

Drug: AMG 706

AMG 706 125 mg daily continuously (Arm A)

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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