This study is designed as a phase 1 dose escalation study followed by a randomised phase II study. The study will be performed in three different centres: Addenbrooke \& Cambridge university (Cambridge, UK), Netherlands Cancer Institute Amsterdam), and Vall d'Hebron Hospital (Barcelona, Spain). Three to six patients will be followed for one completed cycle of therapy (28 days) and subsequent enrolment of new cohorts will be based on the safety assessment in that first cycle and the documentation of dose limiting toxicities. To determine the safety and efficacy of tamoxifen in combination with the isoform selective Pi3K inhibitor GDC-0032 compared with tamoxifen alone.
To determine the recommended phase II dose (RPTD) of GDC-0032 in combination with tamoxifen in hormone receptor positive, HER2 negative metastatic breast cancer patients who have progressed after prior endocrine treatment .Description of toxicity profile, severity and frequency of adverse events (observed with the combination of GDC-0032 and tamoxifen To evaluate the safety and tolerability of GDC-0032 in combination with tamoxifen, recording adverse events using CTCAE v. 4.0 criteria To describe the pharmacokinetics of GDC-0032 in combination with tamoxifen To investigate the possibility of major drug-drug interactions (PK) To obtain proof of target inhibition by selected pharmacodynamic measurements To look for preliminary evidence of anti-tumour activity To assess the status of potential biomarkers for drug response like PIK3CA gene mutations, relevant proteins and phospho-proteins in the PI3K pathway, circulating tumour DNA (ct-DNA) To assess germline DNA sequence for pharmacogenetics studies
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
189
Gustave Roussy
Paris, France
Antoni van Leeuwenhoek
Amsterdam, Netherlands
Reinier de Graaf Gasthuis
Delft, Netherlands
Deventer Ziekenhuis
Deventer, Netherlands
Ziekenhuis Groep Twente
Hengelo, Netherlands
MUMC
Maastricht, Netherlands
Haaglanden Medisch Centrum
The Hague, Netherlands
Hospital Germans Trias i Pujol
Badalona, Spain
Vall d'Hebron University Hospital/VHIO
Barcelona, Spain
Hospital Clínic de Barcelona
Barcelona, Spain
...and 4 more locations
Number of patients with MTD toxicity
MTD toxicity will be assessed in the first 28 days of treatment
Time frame: 4 weeks
Safety Number of patients with adverse events
Number of patients with adverse events
Time frame: 2 year
Pharmacokinetics Number of patients with germline DNA sequence
Number of patients with germline DNA sequence
Time frame: 12 months
Response Number of patients with a response to protocol treatment
Number of patients with a response to protocol treatment
Time frame: 2 year
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