Efficacy and Safety of AZD4547 Versus Paclitaxel in Patients With Advanced Gastric or Gastro-oesophageal Cancer

A Randomised Open-Label Phase II Study to Assess the Efficacy & Safety of AZD4547 Monotherapy Versus Paclitaxel in Patients With Advanced Gastric Adenocarcinoma (Inc. Adenocarcinoma of the Lower Third of the Oesophagus or the Gastro-Oesophageal Junction)With FGFR2 Polysomy or Gene Amplification.

The purpose of this study is to assess the efficacy, safety and tolerability of AZD4547 compared with paclitaxel in patients with advanced gastric or lower-oesophageal cancer whose tumours are found to have FGFR2 polysomy or gene amplification.

A Randomised Open-Label Phase IIa Study to Assess the Efficacy and Safety of AZD4547 monotherapy versus paclitaxel in Patients with Advanced Gastric or Gastro-oesophageal Junction Cancer with FGFR2 Polysomy or Gene Amplification (SHINE study). Patients were to be assigned to strata by FGFR2 status of: polysomy, low or high gene amplification.

Inclusion Criteria:

• Female or male aged 25 or over
• Histological diagnosis of locally advanced or metastatic gastro adenocarcinoma (including adenocarcinoma of the lower third of the oesophagus or the gastro oesophageal junction )
• Radiographically confirmed progression after 1 prior chemotherapy or chemoradiotherapy for gastric cancer. Suitable for and expected to benefit from paclitaxel monotherapy.
• At least one lesion, not previously irradiated, that has baseline at least 10mm in the longest diameter for non nodal lesions and is assessed by Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI)
• Provision of either an archival tumour sample or a fresh tumour sample for confirmation of FGFR2 polysomy/gene amplification

Exclusion Criteria:

• Prior exposure to AZD4547 or history of hypersensitivity other drugs similar in structure or class to AZD4547. Hypersensitivity to paclitaxel or formulated in cremophor EL (polyoxyethylated castor oil)
• Prior taxane treatment for gastric cancer with the exception of adjuvant/neo-adjuvant therapy given > 6 months; Major surgery, radiotherapy with wide field of radiation or any cancer treatment within 4 weeks before the first dose of the study treatment
• With the exception of alopecia, any unresolved toxicities from prior therapy with a Common Terminology Criteria for AE (CTCAE) grade >1 at the time of starting study treatment.
• Blood and Echocardiogram (ECG) readings that are deemed to be abnormal by falling outside of the reference ranges in the protocol inclusion/exclusion section.
• Taking other regular medication that are predicted to interact with AZD4547 due to their route of metabolism.