Safety and efficacy of AZD4547 versus paclitaxel in Advanced Gastric or Gastro-oesophageal Junction Cancer patients

Conditions: FGFR, Amplification, polysomy, gastro-oesophageal junction cancer, lower third oesophageal cancer, gastric cancer, randomised, efficacy
MedDRA version: 14.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10063916Term: Metastatic gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10017761Term: Gastric cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10061967Term: Gastric cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10030155Term: Oesophageal carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 14.1Level: PTClassification code 10030159Term: Oesophageal carcinoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10017765Term: Gastric cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: LLTClassification code 10026104Term: Malignant neoplasm of lower third of esophagusSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2010-023377-19-DE

Lead Sponsor: AstraZeneca

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 160

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 first line treatment for advanced/metastatic gastric cancer. Suitable for and expected to benefit from paclitaxel monotherapy
At least one lesion, not previously irradiated, that at baseline is equal to or larger than 10mm in the longest diameter for non nodal lesions with 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 by the sponsor approved laboratory. Patients with FGFR2 polysomy or gene amplified tumours will be eligible for the main study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 Cremaphor EL (polyoxyethylated castor oil)
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 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the efficacy of AZD4547 compared with paclitaxel by assessment of Progression-Free Survival (PFS) in all randomised patients and also in the patients with tumours that have FGFR2 amplification (FISH score 6) alone.;Secondary Objective: Efficacy endpoints (Overall Survival, Objective Response Rate & %<br>patients without progressive disease at 8 weeks)<br>Safety & tolerability<br>AZD4547 PK<br>AZD4547 exposure/PD endpoint relationships<br>Quality of life & disease symptoms;Primary end point(s): Investigate the efficacy of AZD4547 compared with paclitaxel by assessment of Progression-Free Survival (measured by RECIST 1.1 or death) in all randomised patients and also in the patients with tumours that have FGFR2 amplification (FISH score 6) alone;Timepoint(s) of evaluation of this end point: RECIST assessments will be performed at baseline and every 8 weeks until progression

Secondary Outcome Measures

Name	Time	Method