Trastuzumab in Combination With AMG 479 in HER-2 Overexpressing MBC Progressing on Trastuzumab

NCT01479179 | Withdrawn Phase 1

• 1 other identifier: 2009-0542
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of Phase 1 of this clinical research study is to test the safety and tolerability of AMG 479 when given with trastuzumab. The goal of Phase 2 of this clinical research study is to learn if the combination of AMG 479 and trastuzumab can help to control breast cancer. AMG 479 is designed to block tumor cells from growing and spreading. Trastuzumab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell.

Conditions

Breast Cancer

Keywords

Breast Cancer; Metastatic Breast Cancer; HER-2-overexpressing breast cancer; Human epidermal growth factor receptor; AMG 479; Trastuzumab; Herceptin

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Maximum tolerated dose (MTD) is highest dose for which one or fewer dose limiting toxicities (DLTs) are experienced in 6 participants. DLT is defined as a grade 3, or higher hematological or non-hematological toxicity related to study (AMG-479) drug or combination of AMG 479 and trastuzumab therapy during first cycle (21 days).

  After first 21 day cycle

Secondary Outcomes (1)

• Clinical Benefit Rate (CBR)

  Baseline to 24 weeks

Study Arms (1)

AMG 479 + Trastuzumab

EXPERIMENTAL

AMG 479 18 mg/kg or 12 mg/kg intravenously (IV) 30 minutes after trastuzumab. Trastuzumab loading dose (Week 1) 8 mg/kg IV over 90 minutes; maintenance dose 6 mg/kg IV over 30 minutes every 3 weeks.

Drug: AMG 479; Drug: Trastuzumab

Interventions

AMG 479 DRUG

Phase I Starting Dose: 18 mg/kg by vein on Day 1 of a 21 day cycle. Phase II Starting Dose: Maximum tolerated dose from Phase I.

AMG 479 + Trastuzumab

Trastuzumab DRUG

Phase I and II Starting Dose: 8 mg/kg by vein on Day 1 of a 21 day cycle. Phase I and II Maintenance Dose: 6 mg/kg by vein on Day 1 of a 21 day cycle.

Also known as: Herceptin

AMG 479 + Trastuzumab

Eligibility Criteria

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

You may qualify if:

• History of biopsy-proven HER-2-overexpressing breast cancer and radiographic evidence of metastatic disease. The HER-2 status can be determined either by immunohistochemistry (score, 3+) or by fluorescence in situ hybridization.
• Patients must have received anthracycline-, taxane- and capecitabine-based chemotherapy for breast cancer. In addition, patients must have developed progressive disease to trastuzumab- or lapatinib-based therapy within the last 3 months. Patients who develop metastatic breast cancer within 3 months after receiving trastuzumab or lapatinib in the adjuvant and/or neoadjuvant setting are eligible. Three prior lines of HER2-directed therapy (containing either trastuzumab or lapatinib) for metastatic breast cancer are allowed.
• Woman \>/=18 years old.
• Performance status 0-2 (by Eastern Cooperative Oncology Group {ECOG} scale).
• Continuation from # 5: Serum creatinine \</= 1.5 x the ULN or calculated creatinine clearance (by Cockcroft-Gault formula) \>/=40 mL/min; Aspartate aminotransferase (AST) \</= 2.5 x ULN; Alanine aminotransferase (ALT) \</= 2.5 x ULN; Alkaline phosphatase \</= 2.5 x ULN (\</= 5 x ULN with bone/liver metastases ); Bilirubin \</= 1.5 x ULN.
• Glycosylated hemoglobin (HgbA1c)\</= 8%
• Fasting blood glucose \</= 160 mg/dL (Fasting will require subjects to refrain from all food and beverage \[except water\] for at least 8 hours). Documentation will confirm patient compliance with nothing by mouth (NPO) status prior to lab exam.
• Patients must not be pregnant. A pregnancy test will be obtained if the patient is a woman of child-bearing potential, defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months).
• Patients must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>/= 20 mm with conventional techniques, including palpation, plain x-ray, or magnetic resonance imaging (MRI), or or \>/= 10 mm with spiral computed tomography (CT) scan. Bone metastases and pleural effusions are not considered measurable disease.
• Patients may not be receiving any other investigational agents within 30 days of registration.
• Left ventricular ejection fraction determined by echocardiogram or multiple-gated acquisition scan (MUGA) (cardiac scan) must be 50% or higher.

You may not qualify if:

• Central nervous system (CNS) metastases , unless previously treated by either radiation therapy and/or surgical resection, clinically stable and off corticosteroids. Subjects with a history of CNS metastases that are both treated and stably controlled are eligible if all of the following apply: therapy has been administered (surgery and/or radiation therapy); there is no additional treatment planned for brain metastases; the subject is clinically stable; the subject is off corticosteroids or on a stable dose of corticosteroids for at least 14 days prior to enrollment
• Prior malignancy (other than in situ cervical cancer, or basal cell or squamous cell carcinoma of the skin), unless treated with curative intent and without evidence of disease for 3 years or longer.
• Administration of other prior anticancer therapies within 4 weeks of enrollment, except Trastuzumab and Lapatinib.
• Toxicities related to prior anticancer treatment (except alopecia) that have not resolved to \</= grade 1 according to common terminology criteria for adverse events (CTCAE V4.0) before registration or prior to start of therapy.
• Prior treatment with investigational treatment targeted to IGF axis including, but not limited to, CP-751,871, IM-A12, RO4858696.
• Previous exposure to AMG 479.
• Currently receiving systemic antibiotic therapy for the treatment of an active infection.
• History of bleeding diathesis.
• Known positive test for human immunodeficiency virus, or chronic hepatitis B or C infection.
• Any co-morbid medical condition that may put the subject at significant risk for toxicity.
• Major surgical procedure within 28 days of registration (prior to the start of therapy).
• Minor surgical procedures within 7 days of registration although placement of central access device, fine needle aspiration, thoracentesis or paracentesis \> 1 day before registration is acceptable.
• Known inability to tolerate intravenous (IV) drug administration.
• Has not yet completed at least 30 days before registration since ending other investigational device or drug study(s)
• Subject has known sensitivity to any of the products to be administered during dosing.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Amgen: collaborator

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ganitumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Francisco J. Esteva, MD,PHD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2011
• First Posted: November 24, 2011
• Study Start: November 1, 2012
• Primary Completion: November 1, 2015
• Last Updated: October 26, 2016

Record last verified: 2016-10