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Termination of study enrolment to Part C, Cohort 3 (08 July 2013) was based on the analysis of data from Study D2610C00004.
Data were available from 33 patient
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This study is primarily designed to assess the safety and tolerability of AZD4547 at increasing doses in patients with advanced solid malignancies and for whom no standard medication options are available. It also assesses the blood levels and action of AZD4547 in the body over a period of time.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A | Experimental | Ascending doses of AZD4547 administered orally to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD) |
|
| Part B | Experimental | Dose expansion phase, at the RD defined in Part A |
|
| Part C | Experimental | Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD4547 | Drug | Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Who Experienced at Least 1 AE | To investigate the safety and tolerability of AZD4547. System organ class (SOC), preferred term (PT), duration and severity all recorded. | AEs are monitored from screenng through to 30 day follow up period |
| Number of Participants Who Experienced at Least 1 Causally Related AE. | To investigate the safety and tolerability of AZD4547. A causally related AE is an AE deemed to be causally related to AZD4547. | AEs are continually assessed from screening up to 30 day FU period |
| Number of Participants With at Least 1 AE of CTCAE >=G3 | To investigate the safety and tolerability of AZD4547 | Ongoing up to discontinuation up to 30 day FU. |
| Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3 | To investigate the safety and tolerability of AZD4547 | Ongoing up to discontinuation up to 30 day FU. |
| Number of Participants Who Experienced at Least One SAE | To investigate the safety and tolerability of AZD4547. A SAE (Serious Adverse Event) is and AE (adverse Event) which fulfills one of the following criteria that the PI assesses closely such as results in death, immediately life-threatening, requires hospitalisation or prolongation of, results in significant disability, results in birth defect, may jepardise the patient or require intervention to prevent any of the previous outcomes. | Serious Adverse Events (SAEs) are continually assessed from Screening up to the end of the 30 day FU period. |
| Number of Participants With at Least 1 Causally Related SAE |
| Measure | Description | Time Frame |
|---|---|---|
| AUC(0-infinity) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK samples out to 96 hours "0 to 96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fabrice André, Dr | Institut de cancérologie Gustave Roussy | Principal Investigator |
| Donal Landers, Dr | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Stanford | California | 94305 | United States | ||
| Research Site |
In Parts A and B, a single dose was followed by a Washout Period of 5 to 10 days before multiple dosing commenced.
First patient enrolled: 21 October 2009 and last patient enrolled: 13 December 2013. This was a multicentre study conducted at a total of 29 centres in 7 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A | Dose escalation |
| FG001 | Part B | Dose expansion phase (80mg bd tablet) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| AZD4547 | Drug | Patients start at a dose of 80 mg twice daily, with no washout |
|
| AZD4547 | Drug | Single dose is followed by washout 5-10 days before multiple dose |
|
To investigate the safety and tolerability of AZD4547: SAEs are assessed and deemed as causally related or not to AZD4547
| SAEs are continually monitored from screening to end of 30 FU period |
| Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR) |
To obtain a preliminary assessment of the anti tumour activity of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1. Objective response = CR + PR; CR=disappearance of all target lesions and PR is >=30% reduction in sum of longest diameter of target lesions |
| Baseline assessment, then assessment every 6 weeks after start of treatment until objective disease progression. |
| Cmax (ng/mL) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
| Css,Max (ng/mL) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK samples out to 96 hours "0-96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
| AUC,ss(0-infinity) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Research Site | New Haven | Connecticut | 06520 | United States |
| Research Site | Detroit | Michigan | 48201 | United States |
| Research Site | New York | New York | 10021 | United States |
| Research Site | Philadelphia | Pennsylvania | 19111 | United States |
| Research Site | Nashville | Tennessee | 37232 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| Research Site | Pierre-Bénite | 69495 | France |
| Research Site | Villejuif | 94805 | France |
| Research Site | Cologne | 50924 | Germany |
| Research Site | Frankfurt | 60488 | Germany |
| Research Site | Freiburg im Breisgau | 79106 | Germany |
| Research Site | Naples | 80131 | Italy |
| Research Site | Rozzano | 20089 | Italy |
| Research Site | Amsterdam | 1066 CX | Netherlands |
| Research Site | Rotterdam | 3015 CE | Netherlands |
| Research Site | Badajoz | 06008 | Spain |
| Research Site | Majadahonda | 28222 | Spain |
| Research Site | Valencia | 46010 | Spain |
| Research Site | Valencia | 46026 | Spain |
| Research Site | Birmingham | B9 5SS | United Kingdom |
| Research Site | Edinburgh | EH4 2XU | United Kingdom |
| Research Site | Glasgow | G12 0YN | United Kingdom |
| Research Site | London | W12 0NN | United Kingdom |
| Research Site | London | W1G 6AD | United Kingdom |
| Research Site | Manchester | M20 4BX | United Kingdom |
| Research Site | Newcastle upon Tyne | NE7 7DN | United Kingdom |
| Research Site | Wolverhampton | WV10 0QP | United Kingdom |
| FG002 |
| Part C |
Dose expansion in patients with FGFR gene-amplified tumours |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part B | Dose expansion phase (80mg bd tablet) |
| BG001 | Part C (FISH Ratio >= 2) | Dose expansion in patients with FGFR gene-amplified tumours |
| BG002 | Part C (FISH Ratio < 2 ) | Dose expansion in patients with FGFR gene-amplified tumours |
| BG003 | Part A | Dose escalation |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | AUC(0-infinity) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | PK samples out to 96 hours "0 to 96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
|
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR) | To obtain a preliminary assessment of the anti tumour activity of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1. Objective response = CR + PR; CR=disappearance of all target lesions and PR is >=30% reduction in sum of longest diameter of target lesions | Efficacy/Tumour response: All dosed patients meeting the final FISH 6 score criteria with a baseline tumour assessment and had a FGFR1 FISH ratio ≥2 if the patient was from Part C | Posted | Number | Patients | Baseline assessment, then assessment every 6 weeks after start of treatment until objective disease progression. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Cmax (ng/mL) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Css,Max (ng/mL) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | PK samples out to 96 hours "0-96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | AUC,ss(0-infinity) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
|
| |||||||||||||||||||||||||||||||||||
| Primary | Number of Patients Who Experienced at Least 1 AE | To investigate the safety and tolerability of AZD4547. System organ class (SOC), preferred term (PT), duration and severity all recorded. | Posted | Number | Participants | AEs are monitored from screenng through to 30 day follow up period |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants Who Experienced at Least 1 Causally Related AE. | To investigate the safety and tolerability of AZD4547. A causally related AE is an AE deemed to be causally related to AZD4547. | Posted | Number | Participants | AEs are continually assessed from screening up to 30 day FU period |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With at Least 1 AE of CTCAE >=G3 | To investigate the safety and tolerability of AZD4547 | Posted | Number | Participants | Ongoing up to discontinuation up to 30 day FU. |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3 | To investigate the safety and tolerability of AZD4547 | Posted | Number | Participants | Ongoing up to discontinuation up to 30 day FU. |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants Who Experienced at Least One SAE | To investigate the safety and tolerability of AZD4547. A SAE (Serious Adverse Event) is and AE (adverse Event) which fulfills one of the following criteria that the PI assesses closely such as results in death, immediately life-threatening, requires hospitalisation or prolongation of, results in significant disability, results in birth defect, may jepardise the patient or require intervention to prevent any of the previous outcomes. | Posted | Number | Number of participants | Serious Adverse Events (SAEs) are continually assessed from Screening up to the end of the 30 day FU period. |
| ||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With at Least 1 Causally Related SAE | To investigate the safety and tolerability of AZD4547: SAEs are assessed and deemed as causally related or not to AZD4547 | Posted | Number | Number of participants | SAEs are continually monitored from screening to end of 30 FU period |
|
|
AEs were collected on a continual basis from Screening up until the end of the 28 day follow up period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part B | Dose expansion phase (80mg bd tablet) | 1 | 6 | 6 | 6 | ||
| EG001 | Part C (FISH Ratio >= 2) | Dose expansion in patients with FGFR gene-amplified tumours | 10 | 33 | 33 | 33 | ||
| EG002 | Part C (FISH Ratio < 2) | Dose expansionj in patients with FGFR gene-amplified tumours | 3 | 12 | 12 | 12 | ||
| EG003 | Part A | Dose escalation | 11 | 43 | 43 | 43 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Renal failure | Renal and urinary disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| ALT increased | Investigations | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| GGT increased | Investigations | MedDRA Version 14.1. | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Pelvi-ureteric obstruction | Renal and urinary disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Tumour associated fever | General disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA Version 14.1. | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Chorioretinopathy | Eye disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Atrial flutter | Vascular disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Bile duct obstruction | Hepatobiliary disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Decreased appetite | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Euthanasia | Social circumstances | MedDRA Version 14.1. | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Hypotension | Nervous system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Pericardial effusion | Blood and lymphatic system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 14.1. | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA Version 14.1. | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Stomatis | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dyspepsia | Nervous system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Muscle spasms | Nervous system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Breath sounds abnormal | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Ageusia | Metabolism and nutrition disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Oedema peripheral | Eye disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| ALT increased | Investigations | MedDRA Version 14.1. | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 14.1. | Systematic Assessment |
| |
| Insomnia | Nervous system disorders | MedDRA Version 14.1. | Systematic Assessment |
|
Due to early termination no AUC(inf), Cmax, Css,max and AUC,ss for Part C (PK). Data from 33 patients after 22 days of multiple dosing in Part A & limited data for part B only.
1 subject not dosed, so pre-stated subject number 95, total with data 94.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Donal Landers | AstraZeneca | +44 1625 231890 | Donal.Landers@astrazeneca.com |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C572463 | AZD4547 |
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| Male |
|
Dose expansion in patients with FGFR gene-amplified tumours |
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| Counts |
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| Participants |
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| Participants |
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| Participants |
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