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 |
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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) |
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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) |
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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) |
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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) |
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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) |
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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) |
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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) |
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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) |
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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 |
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. |
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E.2.2 | Secondary objectives of the trial |
Efficacy endpoints (Overall Survival, Objective Response Rate & % patients without progressive disease at 8 weeks)
Safety & tolerability
AZD4547 PK
AZD4547 exposure/PD endpoint relationships
Quality of life & disease symptoms |
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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 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 |
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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 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. |
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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 |
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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 |
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E.5.2 | Secondary end point(s) |
Investigate the efficacy of AZD4547 compared with paclitaxel by comparison of Overall Survival (OS) in all randomised patients & also in the patients with tumours that have FGFR2 amplification (FISH score 6) alone
Investigate the efficacy of AZD4547 vs paclitaxel by comparison of the change in tumour size at 8 weeks (as measured by RECIST) in all randomised patients & also in the patients with tumours that have FGFR2 amplification (FISH score 6) alone
Efficacy of AZD4547 vs paclitaxel by objective response rate and duration of response (% of Patients with Complete or Partial Response as measured by RECIST 1.1) in randomized patients and in patients with FGFR2 amplified tumours (FISH 6) alone
Investigate the efficacy of AZD4547 vs paclitaxel by assessment of the % of patients without progressive disease (as measured by RECIST 1.1) at 8 weeks in all randomised patients & in the patients with tumours that have FGFR2 amplification (FISH6) alone
Investigate pharmacokinetics of AZD4547 in patients receiving AZD4547
Investigate possible relationships between plasma AZD4547 and levels of bFGF
Investigate possible relationships between plasma AZD4547 and levels of FGF23
Investigate possible relationships between plasma AZD4547 and levels of phosphate
Safety and tolerability of AZD4547 versus paclitaxel by assessing changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis)
Safety and tolerability of AZD4547 versus paclitaxel in terms of changes from baseline in vital signs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Survival contacts (randomised patients) every 3 mths after discontinuation study drug until either approx. 75% data maturity achieved in FISH6 stratum or approx. 70% data maturity achieved in overall population FISH4-6;RECIST-baseline & wk 8; RECIST-baseline & every 8 wks until progression;RECIST-baseline & wk 8; Plasma AZD4547 measured-pre-interim analysis:Cycle 1-Day7(pre),Day14(pre,0.5-2,5-6,8-12 hrs),Cycle2-Day1(pre),Day 14pre,0.5-2,5-6,8-12 hrs),Post interim analysis:Cycle1-Day7(pre),Day14(pre, 3hr)All patients-0-48hr post last dose;Biomarker samples taken during screening:Cycle1-Day 8&15,Cycle3 Day 1&Day 1 of each subsequent cycle;Lab data -collected from screening to 28 days after study drug discontinuation;Vital signs recorded: screening to 28 days after study drug discontinuation |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
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 |
Bulgaria |
Czech Republic |
France |
Germany |
Hungary |
India |
Italy |
Korea, Republic of |
Romania |
Russian Federation |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 18 |