Phase 1b Study to Evaluate the Safety of AMG 706 in Combination With Paclitaxel or Docetaxel as Treatment for Locally Breast Cancer - Full Text View

Sponsored by:	Amgen
Information provided by:	Amgen
ClinicalTrials.gov Identifier:	NCT00322400

Purpose

This open-label, dose-finding, multi-center study is designed to determine the safety and the maximum tolerated dose of AMG 706 given once daily in combination with either weekly paclitaxel (Arm A) or once-every-3 week docetaxel (Arm B) in subjects with locally recurrent or metastatic breast cancer. Secondarily, this study will evaluate the pharmacokinetic (PK) profile of AMG 706 in both treatment arms, the PK profile of paclitaxel in Arm A and the PK profile of docetaxel in Arm B. Additionally, this study will assess objective tumor response and duration of response. Exploratory endpoints include the investigation of potential biomarker development and to assess the effects of genetic variation in drug metabolism genes, cancer genes and drug target genes on subject response to AMG 706 in combination with paclitaxel or docetaxel.

Condition	Intervention	Phase
Locally Recurrent and Metastatic Breast Cancer	Drug: AMG 706 Drug: Docetaxel Drug: Paclitaxel	Phase I

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Docetaxel Paclitaxel Motesanib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety Study
Official Title:	An Open-Label, Dose-Finding Study to Evaluate the Safety of AMG 706 in Combination With Paclitaxel or Docetaxel as Treatment for Locally Recurrent or Metastatic Breast Cancer

Further study details as provided by Amgen:

Primary Outcome Measures:

Incidence of dose limiting toxicities (DLTs) [ Time Frame: Cycle 1 of treatment. For Arm A, 1 cycle = 28 days. For Arm B, 1 cycle = 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics of AMG 706 when administered with paclitaxel (Arm A) or docetaxel (Arm B) [ Time Frame: Cycle 1 (Arms A and B) and Cycle 2 Arm B only) ] [ Designated as safety issue: No ]
Objective tumor response (complete or partial response) according to modified RECIST [ Time Frame: Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation. ] [ Designated as safety issue: No ]
Incidence of adverse events and clinical laboratory abnormalities not defined as DLTs [ Time Frame: From study entry through 30 days post discontinuation of study treatment ] [ Designated as safety issue: Yes ]
Pharmacokinetics of paclitaxel (Arm A) when administered with AMG 706 [ Time Frame: Cycle 1, D1 and D8 for subjects in Arm A only ] [ Designated as safety issue: No ]
Pharmacokinetics of docetaxel (Arm B) when administered with AMG 706 [ Time Frame: Cycles 1 and 2 for subjects in Arm B only ] [ Designated as safety issue: No ]
Duration of response (calculated for those subjects who respond): time from first objective tumor response to objective disease progression or death. [ Time Frame: Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation. ] [ Designated as safety issue: No ]

Enrollment:	46
Study Start Date:	March 2006
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
B1: Experimental AMG 706 50 mg daily + Docetaxel (100 mg/m2 D1 every 21 days)	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Docetaxel Subjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond.
A4: Experimental 75 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8 and D15 every 28 days)	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Paclitaxel Subjects assigned to Arm A will receive 90 mg/m2 of paclitaxel on Days 1, 8 and 15 repeated every 28 days (1 cycle). On Arm A, AMG 706 will be concurrently administered on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond.
A1: Experimental AMG 706 50 mg daily + Paclitaxel (90 mg/m2 D1, D8, D15 every 28 days)	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Paclitaxel Subjects assigned to Arm A will receive 90 mg/m2 of paclitaxel on Days 1, 8 and 15 repeated every 28 days (1 cycle). On Arm A, AMG 706 will be concurrently administered on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond.
B4: Experimental 75 mg AMG 706 daily + Docetaxel (100 mg/m2, D1 every 21 days)	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Docetaxel Subjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond.
B5: Experimental MTD of AMG 706 + Docetaxel (75mg/m2 D1 every 21 days)	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Docetaxel Subjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond.
B3: Experimental 100 mg AMG 706 daily + Docetaxel (100 mg/m2 on D1 every 21 days)	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Docetaxel Subjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond.
B2: Experimental AMG 706 125 mg daily + Docetaxel (100 mg/m2 D1 every 21 days)	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Docetaxel Subjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond.
A2: Experimental AMG 706 125 mg daily + paclitaxel 90 mg/m2 D1, D8, D15 every 28 days	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Paclitaxel Subjects assigned to Arm A will receive 90 mg/m2 of paclitaxel on Days 1, 8 and 15 repeated every 28 days (1 cycle). On Arm A, AMG 706 will be concurrently administered on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond.
A3: Experimental 100 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8, and D15 every 28 days)	Drug: AMG 706 Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. Drug: Paclitaxel Subjects assigned to Arm A will receive 90 mg/m2 of paclitaxel on Days 1, 8 and 15 repeated every 28 days (1 cycle). On Arm A, AMG 706 will be concurrently administered on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Female 18 years of age or older.
Adequate hematologic, renal and hepatic function.
Competent to comprehend, sign, and date an IRB-approved informed consent form.
Subjects of childbearing potential and sexually active must provide a negative pregnancy test and use accepted and effective method of contraception.

Exclusion Criteria:

Prior taxane-containing treatment within 6 months prior to enrollment.
Prior treatment including chemotherapy and/or endocrine therapy discontinued < 21 days prior to enrollment.
More than one prior systemic chemotherapy for locally recurrent or metastatic breast cancer.
Current or prior history of central nervous system metastases.
History of arterial or venous thrombosis within 1 year prior to enrollment.
History of bleeding diathesis or bleeding within 14 days prior to enrollment.
Radiation therapy to a significant portion of bone marrow or prior history of high-dose chemotherapy requiring bone marrow or stem cell support.
Hypersensitivity to paclitaxel, docetaxel, or drugs using the vehicle cremophor.
Prior VEGFr targeted therapies within 30 days of enrollment.
Any anticoagulant therapy within 7 days prior to enrollment, except for warfarin of less than 2mg per day.
Clinically significant cardiac disease including myocardial infarction or other cardiovascular related event within 1 year before enrollment.
Uncontrolled hypertension (systolic >150 mmHg; diastolic > 90 mmHg).
Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive.
Prior bevacizumab or trastuzumab therapy within 12 weeks of enrollment.
Non-healing wound, ulcer or fracture.
Known history of prior episodes of cholecystitis, prior biliary procedure or prior or ongoing biliary disease.
Unable to take oral medications.
Not recovered from previous therapies.
Major surgery within 28 days prior to enrollment.
Prior malignancy unless treated with curative intent and without evidence of disease for greater than 3 years before enrollment.
Peripheral neuropathy grade > 1 per CTCAE version 3.0

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00322400

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

Responsible Party:	Amgen Inc. ( Global Development Leader )
Study ID Numbers:	20050200
Study First Received:	May 4, 2006
Last Updated:	October 30, 2008
ClinicalTrials.gov Identifier:	NCT00322400
Health Authority:	Australia: Therapeutic Goods Administration; United States: Food and Drug Administration

Keywords provided by Amgen:

Clinical trial
AMG 706
Anti-angiogenesis
Locally Recurrent
Metastatic
Breast Cancer
VEGF
Angiogenesis Inhibitor
Oral

Multi-kinase Inhibitor
Anti-tumor
PDGF receptor
Paclitaxel
Docetaxel
Targeted Therapy
Oncology
Amgen
c-Kit

Study placed in the following topic categories:

Docetaxel
Signs and Symptoms
Skin Diseases
Paclitaxel

Breast Neoplasms
Breast Diseases
Recurrence

Additional relevant MeSH terms:

Disease Attributes
Neoplasms
Pathologic Processes
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Mitosis Modulators
Tubulin Modulators
Antimitotic Agents
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009