Phase I Trial of Afatinib and Trastuzumab in HER2 Overexpressing Cancer.

Phase I Trial of Afatinib in Combination With 3 Weekly Trastuzumab in Patients With Tumours Overexpressing HER2. Once the MTD of Afatinib With 3 Weekly Trastuzumab Was Established the Safety of This Dose Will be Assessed Also in Combination With Weekly Trastuzumab.

The aim of the study is to determine the Maximum Tolerated Dose (MTD) of afatinib in combination with 3-weekly trastuzumab in HER2 overexpressing cancer and to assess the efficacy of afatinib given at the MTD dosage, with 3-weekly trastuzumab in HER2 overexpressing metastatic breast cancer.

Inclusion criteria:

1. Patients aged 18 years and older
2. Patients with cancers overexpressing HER2 by Immunohistochemistry test( IHC) 3+ and/or IHC 2+ with positive gene amplification by FISH (confirmation on archived tissue needed)
3. Written informed consent that is consistent with ICH-GCP guidelines.
4. Patients must be eligible for treatment with trastuzumab.
5. Patients must have adequate organ function (kidney, liver, bone marrow, cardiac)
6. Eastern Cooperative Oncology Group (ECOG) = 0 or 1.
7. Measurable disease according to RECIST 1.1 (Phase Ib).

Exclusion criteria:

1. Active brain metastases.
2. Prior treatment with erbB family targeting therapies within the past four weeks before start of therapy or concomitantly with the trial other than trastuzumab and/or lapatinib.
3. Patients having more than 2 lines of chemotherapy for the treatment of metastatic breast cancer (Phase Ib).