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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Gastro-oesophageal Junction Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: AZD4547
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD4547<br>AZD4547 taken orally in tablet formation, 80mg b.d., in a 2 week on, 1 week off schedule | Drug: AZD4547<br>* Tablets taken, oral, twice daily, commencing with a 2 week on AZD4547, 1 week off AZD4547 schedule.<br>|
| Active Comparator: Paclitaxel<br>Paclitaxel - 80mg/m² as a 1 hour infusion given weekly on days 1, 8 and 15 of a 28 day cycle (up to the maximum number of cycles per local practice) | Drug: paclitaxel<br>* Infusion administered once a week, 3 weeks on and 1 week off<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival | PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression). | Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off) |  | Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week) | 
| Objective Response Rate | ORR=Percentage of patients with at least one visit response of CR (complete response) or PR (partial response) that is confirmed at least 4 weeks later; CR:disappearance of target lesions and no new lesions; PR is at least 30% decrease in sum of diameters of lesions taking as a reference the smallest sum since treatment started. | Week 8 (±1 week) and then every 8 weeks (±1 week) | 
| Percentage Change From Baseline at Week 8 in Target Lesion Size | A negative change denotes a reduction in target lesion size. Percentage change from baseline in tumour size at 8 weeks in target lesion size. | Baseline, Week 8 (±1 week) | 
| Percentage of Patients Without Progressive Disease at 8 Weeks | PD = A ≥ 20% increase in the sum of diameters of target lesions and an absolute increase of ≥ 5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diamters | Week 8 (±1 week) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastro-oesophageal junction cancer, gastric cancer, lower third oesophageal cancer, polysomy, amplification, FGFR