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

NCT00322400 | Completed Phase 1

• 1 other identifier: 20050200
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting toxicities (DLTs)

  Cycle 1 of treatment. For Arm A, 1 cycle = 28 days. For Arm B, 1 cycle = 21 days

Secondary Outcomes (6)

• Pharmacokinetics of AMG 706 when administered with paclitaxel (Arm A) or docetaxel (Arm B)

  Cycle 1 (Arms A and B) and Cycle 2 Arm B only)

• Pharmacokinetics of paclitaxel (Arm A) when administered with AMG 706

  Cycle 1, D1 and D8 for subjects in Arm A only

• Pharmacokinetics of docetaxel (Arm B) when administered with AMG 706

  Cycles 1 and 2 for subjects in Arm B only

• Incidence of adverse events and clinical laboratory abnormalities not defined as DLTs

  From study entry through 30 days post discontinuation of study treatment

• Objective tumor response (complete or partial response) according to modified RECIST

  Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation.

Study Arms (9)

B1

EXPERIMENTAL

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

Drug: Docetaxel; Drug: AMG 706

A4

EXPERIMENTAL

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

Drug: Paclitaxel; Drug: AMG 706

A1

EXPERIMENTAL

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

Drug: Paclitaxel; Drug: AMG 706

B4

EXPERIMENTAL

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

Drug: Docetaxel; Drug: AMG 706

B5

EXPERIMENTAL

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

Drug: Docetaxel; Drug: AMG 706

B3

EXPERIMENTAL

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

Drug: Docetaxel; Drug: AMG 706

B2

EXPERIMENTAL

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

Drug: Docetaxel; Drug: AMG 706

A2

EXPERIMENTAL

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

Drug: Paclitaxel; Drug: AMG 706

A3

EXPERIMENTAL

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

Drug: Paclitaxel; Drug: AMG 706

Interventions

Docetaxel 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.

B1; B2; B3; B4; B5

Paclitaxel 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.

A1; A2; A3; A4

AMG 706 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; A2; A3; A4; B1; B2; B3; B4; B5

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• 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.

  PMID: 22872523 RESULT

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

Docetaxel; Paclitaxel; motesanib diphosphate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2006
• First Posted: May 5, 2006
• Study Start: March 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: January 1, 2012
• Last Updated: July 31, 2013

Record last verified: 2013-07