Phase1b to Evaluate Safety of AMG706 in Combination With Paclitaxel or Docetaxel for Breast Cancer

NCT ID: NCT00322400

Last Updated: 2013-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2012-01-31

Brief Summary

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.

Conditions

Locally Recurrent and Metastatic Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

B1

AMG 706 50 mg daily + Docetaxel (100 mg/m2 D1 every 21 days)

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

A4

75 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8 and D15 every 28 days)

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

A1

AMG 706 50 mg daily + Paclitaxel (90 mg/m2 D1, D8, D15 every 28 days)

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

B4

75 mg AMG 706 daily + Docetaxel (100 mg/m2, D1 every 21 days)

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

B5

MTD of AMG 706 + Docetaxel (75mg/m2 D1 every 21 days)

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

B3

100 mg AMG 706 daily + Docetaxel (100 mg/m2 on D1 every 21 days)

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

B2

AMG 706 125 mg daily + Docetaxel (100 mg/m2 D1 every 21 days)

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

A2

AMG 706 125 mg daily + paclitaxel 90 mg/m2 D1, D8, D15 every 28 days

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

A3

100 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8, and D15 every 28 days)

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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.

AMG 706

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

References

De Boer RH, Kotasek D, White S, Koczwara B, Mainwaring P, Chan A, Melara R, Ye Y, Adewoye AH, Sikorski R, Kaufman PA. Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients with metastatic breast cancer. Breast Cancer Res Treat. 2012 Aug;135(1):241-52. doi: 10.1007/s10549-012-2135-0. Epub 2012 Jul 29.

Reference Type: RESULT

PMID: 22872523 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20050200

Identifier Type: -

Identifier Source: org_study_id