NCT02285179

Clinical Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen

Phase I/Prospective Randomized Phase II Trial Of the Safety and Efficacy of Tamoxifen in Combination With GDC-0032 Compared With Tamoxifen alONe.

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 189 (actual)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	GDC-0032	Dose of GDC-0032 given orally, once daily (total daily dose) level -1: 2 mg Q.O.D GDC-0032 level 1: (starting) 2 mg QD for 21 days, 7 days off and tamoxifen 20 mg qd level 2: 4 mg QD for 21 days, 7 days off and tamoxifen 20 mg qd
DRUG	Tamoxifen	daily dose of 20 mg

Timeline

• Start date: 2014-11-01
• Primary completion: 2022-05-01
• Completion: 2022-05-01
• First posted: 2014-11-06
• Last updated: 2022-10-12

Locations

14 sites across 4 countries: France, Netherlands, Spain, United Kingdom