Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00511459
First received: August 2, 2007
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.

AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.


Condition Intervention Phase
Locally Recurrent and Metastatic Breast Cancer
Drug: AMG 386 Placebo
Drug: AMG 386
Drug: Bevacizumab
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, 4-Arm, Placebo-Controlled Phase 2 Trial of AMG 386 in Combination With Bevacizumab and Paclitaxel or AMG 386 Plus Paclitaxel as First-Line Therapy in Subjects With Her2-Negative, Metastatic or Locally Recurrent Breast Cancer

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 3 YEARS ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective Response (OR) [ Time Frame: 3 YEARS ] [ Designated as safety issue: No ]
  • Duration of Response (DOR) [ Time Frame: 3 YEARS ] [ Designated as safety issue: No ]
  • Time to response [ Time Frame: 3 YEARS ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 3 YEARS ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: 3 YEARS ] [ Designated as safety issue: No ]
  • Incidence of AEs and significant laboratory changes [ Time Frame: 3 YEARS ] [ Designated as safety issue: Yes ]
  • AMG 386 Pharmakokinetic parameters [ Time Frame: 3 YEARS ] [ Designated as safety issue: No ]
  • Incidence of the occurrence of anti-AMG 386 antibody formation [ Time Frame: 3 YEARS ] [ Designated as safety issue: No ]

Estimated Enrollment: 220
Study Start Date: July 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW
Drug: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Drug: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Drug: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Experimental: D
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW
Drug: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Drug: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Experimental: B
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW
Drug: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Drug: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Drug: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Active Comparator: C
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW
Drug: AMG 386 Placebo
AMG 386 Placebo [blinded]
Drug: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Drug: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects must have histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
  • Measurable or non-measurable disease per modified RECIST guidelines
  • ECOG of 0 or 1 (within 14 days prior to randomization)
  • Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to randomization:

    • Cardiac function, as follows:

  • Normal sinus rhythm (no significant ECG changes)
  • Left ventricular ejection fraction ≥ LLN, as determined by echocardiogram or MUGA scan, according to institutional standards within 28 days prior to randomization

Exclusion Criteria:

  • Inflammatory Breast Cancer
  • Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral neuropathy > grade 1 at randomization
  • History of arterial or venous thrombosis, including transient ischemic attack (TIA), within 1 year prior to randomization
  • Adjuvant or neoadjuvant taxane treatment within 12 months of randomization. Any other adjuvant chemotherapy regimen must be discontinued at least 21 days prior to randomization
  • Prior chemotherapy, vaccine, or biological therapy for locally recurrent or metastatic breast cancer (prior endocrine therapy is permitted)
  • Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic chemoembolization on all sites of disease unless disease progression was subsequently documented 14 days prior to randomization.
  • Overexpression of HER-2 (gene amplification by FISH or 3+ over expression by immunohistochemistry).
  • Current or prior history of central nervous system metastasis
  • History of bleeding diathesis or clinically significant bleeding within 6 months prior to randomization
  • Major surgical procedure within 28 days prior to randomization
  • Open breast biopsy within 14 days prior to randomization
  • Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of first dose
  • Prior malignancy (other than thyroid cancer, in situ cervical cancer, or basal cell cancer of the skin, treated with curative intent and without evidence of disease for ≥ 3 years prior to randomization)
  • Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication
  • Non-healing wound, ulcer or fracture
  • Known hypersensitivity to paclitaxel or drugs using the vehicle cremophor
  • Known hypersensitivity to bacterial proteins, or any of the drugs required in this study
  • Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
  • Known active or chronic hepatitis
  • Uncontrolled hypertension as defined as systolic blood pressure ≥ 150 mm Hg and diastolic blood pressure ≥ 90 mm Hg. Anti-hypertensive medications are allowed if the subject is stable on their current dose at the time of randomization
  • Currently or previously treated with any VEGF or VEGFr inhibitor, including but not limited to, bevacizumab, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AEE-788, BAY 43-9006 (sorafenib) and AMG 706.
  • Treatment with coumarin-type anticoagulants, (other than low dose prophylaxis for central venous catheters ≤ 1mg/day) within 7 days prior to randomization
  • Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2 including, but not limited to, AMG 386, XL880, XL820
  • Treatment with immune modulators such as cyclosporine and tacrolimus within 30 days prior to randomization
  • Concomitant therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMS), given for breast cancer prevention or for osteoporosis. Subjects must have discontinued these agents 28 days prior to randomization
  • Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00511459

  Show 77 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00511459     History of Changes
Other Study ID Numbers: 20060341
Study First Received: August 2, 2007
Last Updated: March 27, 2014
Health Authority: Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information
Austria: Bundesamt für Sicherheit im Gesundheitswesen
Belgium: Directorate-General for Medicinal Products
Denmark: Laegemiddelstyrelsen
Finland: Lääkelaitos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: Medisch Centrum Rijnmond_Zuid, lcatie Zuider
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amgen:
Randomized
4-Arm
Placebo controlled
Phase 2 Trial
AMG 386
Paclitaxel
Bevacizumab
First-line Therapy
Her-2 Negative
Metastatic or Locally Recurrent Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Bevacizumab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014