E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
FGFR, Amplification, polysomy, gastro-oesophageal junction cancer,
lower third oesophageal cancer, gastric cancer, randomised, efficacy |
|
E.1.1.1 | Medical condition in easily understood language |
stomach and food-pipe cancer, anti-tumour activity, high number of copies of gene driving cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063916 |
E.1.2 | Term | Metastatic gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017761 |
E.1.2 | Term | Gastric cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061967 |
E.1.2 | Term | Gastric cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030159 |
E.1.2 | Term | Oesophageal carcinoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017765 |
E.1.2 | Term | Gastric cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026104 |
E.1.2 | Term | Malignant neoplasm of lower third of esophagus |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030155 |
E.1.2 | Term | Oesophageal carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigate the efficacy of AZD4547 vs paclitaxel by assessment of Progression-Free Survival (PFS) in: all randomised patients, patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone |
|
E.2.2 | Secondary objectives of the trial |
Overall Survival, Objective Response Rate, % patients without progression & change in tumour size at 8 weeks, duration of responseSafety & tolerabilityAZD4547 PK & exposure/PD endpoint relationshipQuality of life, disease symptoms, WHO performance status |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 benefitfrom paclitaxel monotherapyAt least one lesion, not previously irradiated, that at baseline is equal to or larger than 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 |
|
E.4 | Principal exclusion criteria |
Prior exposure to AZD4547 or history of hypersensitivity other drugs similar in structure or class to AZD4547. Hypersensitivity to paclitaxel orformulated in Cremaphor EL (polyoxyethylated castor oil)Prior taxane treatment for gastric cancer with the exception of adjuvant/neo-adjuvant therapy given > 6 monthsMajor surgery, radiotherapy with wide field of radiation or any cancer treatment within 4 weeks before the first dose of the study treatmentWith the exception of alopecia, any unresolved toxicities from prior therapy with a Common Terminology Criteria for AE (CTCAE) grade >1 atthe 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. |
|
E.5 End points |
E.5.1 | 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 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
RECIST assessments will be performed at baseline and every 8 weeks until progression |
|
E.5.2 | Secondary end point(s) |
Investigate the efficacy of AZD4547 vs paclitaxel by comparison of Overall Survival in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone.Investigate the efficacy of AZD4547 vs. paclitaxel by comparison of the change in tumour size at 8 weeks in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone.Efficacy of AZD4547 vs paclitaxel by comparison of objective response rate and duration of response in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone.Efficacy of AZD4547 vs paclitaxel by comparison of % of patients without progression disease at 8 weeks in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumourshave high FGFR2 amplification alone.Safety and tolerability of AZD4547 vs paclitaxel by assessing changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis), vital signs & adverse events.Investigate pharmacokinetics of AZD4547 in patients receiving AZD4547.Investigate possible relationships between plasma AZD4547 and levels of bFGF, FGF23 & phosphate.Disease-related symptom changes & time to symptom progression in patients receiving AZD4547/paclitaxel in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumourshave high FGFR2 amplification alone.Changes in and time to deterioration of Health Related Quality of Life in patients receiving AZD4547/paclitaxel in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone.Changes in, and time to deterioration of, WHO performance status in patients receiving AZD4547/paclitaxel in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumourshave high FGFR2 amplification alone. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Survival contacts, every 3 months after discontinuation of study drug until maturity of the OS endpointRECIST, baseline and at week 8RECIST, baseline and every 8 weeks until progressionRECIST, baseline and at week 8Lab data, vital signs & adverse events - screening to 28 days after study drug discontinuationAZD4547 (pre-interim) C1-D7 pre, D14 (0,0.5-2, 5-6, 8-12 hrs) C2-D1 pre, D14 (0, 0.5-2, 5-6, 8-12 hrs)(Post interim) C1-D7 pre, D14 (0, 3hr) C2-D1 (pre), D14 (pre, 3hr) All, 0-48hr post last doseScreening, Cycle 1 Day 8 Day 15, Cycle 3 Day 1, Day 1 of each subsequent cycleEORTC QLQ-C30, QLQ-STO22 once every 3 weeks until the end of the follow up periodEORTC QLQ-C30, QLQ-STO22 once every 3 weeks until the end of the follow up periodWHO performance status at all visits |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Brazil |
Bulgaria |
Canada |
Czech Republic |
France |
Germany |
Hungary |
India |
Italy |
Japan |
Korea, Republic of |
Romania |
Russian Federation |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 3 |