Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer

Amgen

Status and phase: Completed; Phase 1

Conditions: Tumors; Metastatic Cancer; Breast Tumors; Breast Cancer; Oncology; Metastases; Locally Recurrent and Metastatic Breast Cancer; Breast Neoplasms; Cancer; Solid Tumors

Treatments: Drug: AMG 386 10 mg/kg, Capecitabine and Lapatinib; Drug: AMG 386 30 mg/kg, Capecitabine and Lapatinib; Drug: AMG 386 30 mg/kg, Paclitaxel and Trastuzumab; Drug: AMG 386 10 mgkg, Paclitaxel and Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00807859

20062042

Details and patient eligibility

About

The purpose of this study is to determine if AMG 386 in combination with either paclitaxel and trastuzumab or capecitabine and lapatinib is safe and well tolerated in subjects with HER2-positive locally recurrent or metastatic breast cancer.

This is an open-label phase 1b trial and has 2 study parts. Study part 1 is a dose escalation study to determine a tolerable dose of AMG 386 in combination with paclitaxel and trastuzumab (cohort A) or with capecitabine and lapatinib (cohort B). Study part 2 is cohort expansion of the tolerable doses determined in part 1.

Enrollment: 65 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease not amenable to any local treatment with curative intent.
• HER2-positive by FISH, CISH, or IHC 3+
• ECOG performance status 0 or 1
• Left ventricular ejection fraction greater than or equal to institutional lower limit of normal
• Adequate laboratory studies (hematological, chemistries and urinalysis)
• Life expectancy greater than or equal to 3 months
• Cohort A only:
• Trastuzumab naïve or trastuzumab in the neo-adjuvant setting
• No clinically significant drop in cardiac function prior exposure to trastuzumab
• No prior chemotherapy for metastatic or locally recurrent breast cancer
• No prior lapatinib therapy
• At least 3 weeks from enrollment since prior chemotherapeutic agents, including taxanes, in the neoadjuvant or adjuvant setting
• At least 3 months from enrollment since prior trastuzumab in the neoadjuvant or adjuvant setting
• Cohort B only:
• Must have failed trastuzumab in the first-line metastatic setting. Trastuzumab must be discontinued for at least 3 weeks prior to enrollment
• Must have received prior chemotherapy as adjuvant therapy or for metastatic disease
• Prior chemotherapy treatment must be discontinued for at least 3 weeks prior to enrollment
• No prior capecitabine
• No prior lapatinib

Exclusion criteria

• Inflammatory breast cancer
• Central nervous system metastasis
• Clinically significant cardiovascular disease
• Radiation therapy ≤ 14 days prior to enrollment.
• Concurrent anticoagulation therapy, excluding aspirin, anti-platelet agents, low molecular weight heparin or low dose warfarin per protocol.
• Uncontrolled hypertension defined as diastolic blood pressure > 90 mmHg OR systolic blood pressure > 140 mmHg.
• Subjects with a history of prior malignancy, except:
• For Cohort B only:
• Current or prior history of long QT syndrome
• Baseline ECG report of QTc interval of > 480 milliseconds
• Severe chronic liver disease (Child Pugh C)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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65 participants in 4 patient groups

Cohort A1

Experimental group

Treatment:

Drug: AMG 386 10 mgkg, Paclitaxel and Trastuzumab

Cohort A3

Experimental group

Treatment:

Drug: AMG 386 30 mg/kg, Paclitaxel and Trastuzumab

Cohort B1

Experimental group

Treatment:

Drug: AMG 386 10 mg/kg, Capecitabine and Lapatinib

Cohort B3

Experimental group

Treatment:

Drug: AMG 386 30 mg/kg, Capecitabine and Lapatinib