Assess the Efficacy of AZD8931 in Combination With Paclitaxel Versus Paclitaxel Alone in Patients With Gastric Cancer

Study Overview
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Brief Summary
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The purpose of the study is to assess the efficacy and safety and PK of AZD8931 plus paclitaxel versus paclitaxel alone in patients with metastatic, gastric or gastro-oesophageal junction, cancer.

Detailed Description
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A Phase IIa Multi-centre Randomised Double-Blind Placebo-controlled Study to Assess the Efficacy, Safety and Pharmacokinetics of AZD8931 in Combination with Paclitaxel versus Paclitaxel alone in Patients with Metastatic, Gastric or Gastro-oesophageal Junction, Cancer who progress following First Line Therapy and are Ineligible for Treatment with trastuzumab by HER2 Status (SAGE)

Official Title
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A Phase IIa Multi-centre Randomised Double-Blind Placebo-controlled Study to Assess the Efficacy, Safety and Pharmacokinetics of AZD8931 in Combination With Paclitaxel Versus Paclitaxel Alone in Patients With Metastatic, Gastric or Gastro-oesophageal Junction, Cancer Who Progress Following First Line Therapy and Are Ineligible for Treatment With Trastuzumab by HER2 Status (SAGE)

Conditions
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Metastatic, Gastric or Gastro-oesophageal Junction, Cancer

Intervention / Treatment
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* Drug: AZD8931
* Drug: Placebo
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 years or older (20 years or older in Japan) Patients must have radiologically confirmed progression following 1st line fluoropyrimidine and platinum based treatment for metastatic gastric cancer (the date of progression and start of first line treatment to be captured on the database) Suitable for paclitaxel therapy. At least one lesion, not previously irradiated and not chosen for a mandatory fresh tumour biopsy during the study screening period, that can be accurately measured at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeat assessment. Ineligible for trastuzumab treatment by local assessment. This should include IHC analysis to determine HER2 status with further testing by FISH/CISH when considered part of local practice. Eligible patients are defined as; HER2 IHC 0, HER2 IHC +1 and +2 Exclusion Criteria: Have received more than 1 prior chemotherapy regimen for metastatic gastric cancer. (chemotherapy as adjuvant treatment is permitted). Any prior taxane therapy (at any time from diagnosis of gastric cancer) Any prior therapy with an inhibitor of ErbB1 (EGFR) or ErbB2 (HER2) (eg, lapatinib) Resting ECG with measurable QTc(F) interval of greater than 480 msec at 2 or more time points within a 24 hour period (see section 6.4.9.1 ) Unresolved toxicity grater than CTCAE grade 2 (except alopecia) from previous anti-cancer therapy

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: AZD8931<br>* 40 mg, oral dose twice daily<br>Drug: Paclitaxel<br>* IV once weekly for 3 weeks followed by a week off.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo, oral dose twice daily<br>Drug: Paclitaxel<br>* IV once weekly for 3 weeks followed by a week off.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tumour Size at 8 Weeks Were Analyzed for Comparing Relative Efficacy of AZD8931 Plus Paclitaxel With Paclitaxel Alone |  | Baseline and 8 weeks, accessed up to data cut off on 4 December 2012 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Were Analysed for Comparing Relative Efficacy of AZD8931 Plus Paclitaxel With Paclitaxel Alone | Time from the date of randomization until the date of objective disease progression (as per RECIST1.1) or the date of death (by any cause in absence of progression). | Baseline and every 8 weeks, accessed up to data cut off on 4 December 2012 | 
| The Objective Response Rate (ORR) Was Analysed for Investigating the Efficacy of AZD8931 Plus Paclitaxel With Paclitaxel Alone | The number of subjects with at least one visit response of CR or PR. (Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), A ≥ 20% increase in the sum of diameters of target lesions and an absolute increase of ≥ 5mm; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Not Evaluable (NE), All target lesion measurements are missing or >1/3 target lesion measurements are missing and sum of diameters of non-missing target lesions does not qualify for PD; Not applicable (NA), No target lesions are recorded at baseline) | Baseline and 8 weeks, accessed up to data cut off on 4 December 2012 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Gastric Cancer who progress following First Line Therapy and are Ineligible for Treatment with trastuzumab by HER2 Status