Status: Closed
Activation Date: 2016APR21
Closing Date: 2017APR20
Phase: I
Description: A Phase 1b Pharmacodynamic Study of Durvalumab (MEDI4736) in Patients with HER-2 Positive Metastatic Breast Cancer (MBC) Receiving Trastuzumab
Eligibility: Patients with histologically and/or cytologically confirmed HER-2 positive metastatic breast cancer. Must have an available formalin fixed paraffin embedded tissue block from primary or metastatic tumour. Patients enrolled to the RP2D / expansion cohort must have accessible disease suitable for biopsy and have consented to biopsy prior to treatment and at the end of cycle 1 (paired biopsies are recommended in all patients). Patients must have measurable disease per RECIST 1.1 and adequate organ function. Age >=18 years. ECOG 0, 1, or 2. Must have had prior exposure to a taxane, trastuzumab and pertuzumab and preferably also prior exposure to TDM-1 (no limit to number of prior regimens). Prior surgery and radiation permitted provided adequate time has elapsed form last dose. No active or prior autoimmune or inflammatory disorders, or history of primary immunodeficiency. No live attenuated vaccination on treatment or within 30 days of either registration or last dose.
Objective: PRIMARY - To determine the recommended phase II dose of durvalumab given to patients with advanced/recurrent HER-2 positive metastatic breast cancer (MBC) who are receiving treatment with trastuzumab. SECONDARY - (1) To describe the toxicities of durvalumab in patients receiving trastuzumab; (2) To evaluate the response rate and clinical benefit rate of durvalumab (measured by RECIST 1.1/Immune Response Criteria) in patients receiving trastuzumab; (3) To assess PD-L1 expression in paired biopsies pre and post treatment with durvalumab as a marker of response/benefit. EXPLORATORY - (1) To perform whole exome sequencing and RNAseq in paired biopsies (pre and post treatment) to explore biological correlates relative to PD-1/PD-L1 and trastuzumab and durvalumab exposure (minimum of 6 patients with paired biopsies); (2) To collect ctDNA as an exploratory marker; (3) To assess T cell and other immune cell subsets in paired biopsies pre and post treatment.
Participation: Limited to invited centres
Lay Description: The main purpose of this study is to determine the best dose of durvalumab in patients with HER-2 positive metastatic breast cancer who are receiving trastuzumab, and to investigate the safety and toxicity of durvalumab when given with trastuzumab, as well as response and clinical benefit of this therapy. Additional research will investigate the effects durvalumab and trastuzumab have on cancer cells, as well as explore immune cell profiles both before and after treatment.
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Hide Tissue Samples
Disease Site | Trial Code | Patients Accrued | Patients - Blocks | Patients - Slides | Patients - Blocks and/or Slides |
IND | I229 | 15 | 14 | 15 | 15 |
(Core size is 0.6 mm)
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Fluid SamplesDisease Site | Trial Code | Patients Accrued | TMA Blocks | Patients on TMA Blocks |
IND | I229 | 15 | 1 | 3 |
Disease Site | Trial Code | Patients Accrued | Patients - Whole Blood | Patients - Cellular Component of Blood | Patients - DNA extracted from Blood | Patients - RNA extracted from Blood | Patients - Plasma | Patients - Serum | Patients - Urine | Patients - Buccal |
IND | I229 | 15 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |