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

Breast Cancer Clinical Trial

Official title: Phase I/II Study of Trastuzumab in Combination With AMG 479, A Fully Human Monoclonal Antibody Against Insulin-Like Growth Factor Type 1 Receptor (IGF-1R), in Patients With HER-2 Overexpressing Metastatic Breast Cancer Progressing on Trastuzumab-Based or Lapatinib-based Therapy

Status Withdrawn

Clinical Trial 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.

Clinical Trial Description

Phase 1 and Phase 2 of the Study:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Groups of 3 participants will be enrolled in the Phase 1 portion of the study. There are 2 dose levels that will be tested in Phase 1.

If you are enrolled in the Phase 1 portion, the dose of AMG 479 you receive will depend on when you joined this study. The first group of participants will receive the higher dose level of AMG 479. If there are intolerable side effects, the next group will receive the lower dose.

If you are enrolled in the Phase 2 portion, you will receive AMG 479 at the highest dose that was tolerated in the Phase 1 portion.

All participants will receive the same dose level of trastuzumab.

Study Drug Administration:

You will receive AMG 479 by vein over 60-120 minutes on Day 1 of each 21-day cycle.

You will receive trastuzumab by vein over 30-90 minutes on Day 1 of each cycle.

If you are already receiving trastuzumab at the time you join the study, you will continue to receive the standard dose of trastuzumab. If the last dose of trastuzumab was given more than 1-3 weeks before you joined the study (depending on the dose previously received), then you will receive a higher "loading" dose of trastuzumab followed by the standard dose.

Study Visits:

At every visit, you will be asked about any side effects you may have had.

Your vital signs will be checked before, during, and after each infusion of AMG 479.

On Day 1 of Cycle 1, blood (about 5 tablespoons) will be drawn for routine tests.

If you are in Phase 1, blood (about 1 tablespoon each time) will be drawn for pharmacokinetic (PK) testing 2 times (before and after the study drug dose) on Day 1 of Cycles 1 and 2. PK testing measures the amount of study drug in the body at different time points.

On Day 8 of Cycle 1, blood (about 1 tablespoon) will be drawn for routine tests.

On Day 15 of Cycle 1:

• You will have a physical exam, including measurement of your weight and vital signs.

• Blood (about 1 tablespoon) will be drawn for routine tests.

• Your performance status and any updates to your medical history will be recorded.

On Day 1 of Cycles 2, 4, and 6, you will have CT or MRI scans to check the status of the disease.

On Day 1 of Cycles 2 and beyond:

• Blood (about 1-2 teaspoons) will be drawn for blood sugar tests. You will need to fast for 8 hours before these tests.

• You will have a physical exam, including measurement of your weight and vital signs.

• Your performance status and any updates to your medical history will be recorded.

• Blood (about 1 tablespoon) will be drawn for routine tests.

You will have a PET-CT scan at Week 3 if you had a PET-CT scan at screening.

On Day 8 of Cycles 1-3, blood (about 1½ teaspoons) will be drawn to check your blood clotting function.

Every 3 months, you will have either an ECHO or MUGA scan to check your heart function.

In certain cases with your doctor's permission, the study visits may occur 1 day earlier or later than described above. If you are having side effects, extra clinic visits may be needed.

Length of Treatment:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment visit.

End of Treatment Visit:

Within 30 days after the last study drug dose:

• You will have a physical exam, including measurement of your weight and vital signs.

• You will be asked if you have had any side effects and about any drugs you may be taking.

• Any updates to your medical history will be recorded.

• Blood (about 3 tablespoons) will be drawn for routine tests.

• You will have a hearing test

• If you have not had one in the last 30 days or after your last treatment, you will have an ECHO or MUGA scan to check your heart function.

• If the doctor thinks it is needed, you will have CT or MRI scans to check the status of the disease.

• If you are in Phase 1, blood (about 1 tablespoon) will be drawn for PK testing.

This is an investigational study. Trastuzumab is FDA approved and commercially available for the treatment of breast cancer. AMG-479 is not FDA approved or commercially available. AMG-479 is currently being used for research purposes only.

Up to 35 patients will take part in this study. All will be enrolled at MD Anderson. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT01479179
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: November 2012