Fibroblast growth factor receptors (FGFR) Inhibition for Epithelial Solid Tumours
| ISRCTN | ISRCTN44149443 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44149443 |
| EudraCT/CTIS number | 2011-004072-10 |
| Secondary identifying numbers | MO11/9803 |
- Submission date
- 24/08/2011
- Registration date
- 14/10/2011
- Last edited
- 26/10/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Dr John Chester
Scientific
Scientific
Clinical Trials Research Unit
University of Leeds
Leeds
LS2 9JT
United Kingdom
| medctfst@leeds.ac.uk |
Study information
| Study design | Dose escalation cohort trial followed by a randomised expansion cohort |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Fibroblast growth factor receptors (FGFR) Inhibition for Epithelial Solid Tumours: a phase Ib trial of AZD4547 in combination with gemcitabine and cisplatin |
| Study acronym | FIESTA |
| Study objectives | This study aims to investigate, for the first time in man, the combination of gemcitabine/cisplatin (GC) with AZD4547. As GC is a standard-of-care for both neoadjuvant and first-line palliative chemotherapy, the three-drug combination of AZD4547 plus GC (AGC) therefore has the potential for improving outcomes in both disease settings. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Epithelial Solid Tumours |
| Intervention | AZD4547 with Gemcitabine and Cisplatin with increasing doses of AZD4547 during the Dose Escalation Cohort. Randomisation between AZD4547 with Gemcitabine and Cisplatin, and Gemcitabine and Cisplatin alone in the Randomised Expansion Cohort |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | AZD4547, cisplatin, gemcitabine |
| Primary outcome measure | 1. Dose-escalation cohort: 1.1. Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) of AZD4547 in combination with GC 1.2. Recommended Dose for Sustained Tolerability (RDST) for use in the randomized expansion cohort of this trial and in subsequent studies. 2. Randomised expansion cohort: 2.1. Relative proportions of participants experiencing any grade 3/4 CTCAE v4.02 toxicity within first cycle of treatment of AGC and GC regimens. |
| Secondary outcome measures | No secondary outcome measures |
| Overall study start date | 01/02/2012 |
| Completion date | 01/07/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 44 |
| Total final enrolment | 28 |
| Key inclusion criteria | 1. Provision of written informed consent 2. Age 25 years or greater 3. Histologically confirmed locally advanced / metastatic non-haematological malignancy 3.1. Dose-escalation cohort 3.2. Any locally-advanced and/or metastatic malignancy for which no recognised standard treatment is available (including tumours refractory to previous standard therapies), and for whom gemcitabine and cisplatin would be appropriate treatment. Any number of previous lines of therapy are permitted OR 3.3. Locally advanced and/or metastatic transitional cell carcinoma, of the urinary tract, as in the randomised expansion cohort 3.4. Dose expansion cohort-Locally advanced and/or metastatic transitional cell carcinoma (pure or mixed histology) of (upper or lower) urinary tract, including bladder cancer. No prior systemic therapy for locally advanced or metastatic disease - patients who have received prior neoadjuvant or adjuvant chemotherapy for potentially-curable urothelial cancer (up to 4 cycles), completed at least 6 months prior to first documented disease progression, will be eligible 4. Radiologically measurable disease (randomised expansion cohort only) 4.1. T4b Nany Many, Tany N2-3 Many or Tany Nany M1 TCC of the urinary tract (as above), not amenable to curative treatment with surgery or radiotherapy 5. Fit to receive cisplatin-containing combination chemotherapy 6. Minimum life expectancy of 18 weeks 7. WHO Performance Status 0-1 8. Adequate renal function [glomerular filtration rate (GFR) greater than or equal to 60ml/min, uncorrected for surface area and measured by isotopic means] 9. Adequate bone marrow function (absolute neutrophil count greater than or equal to 1.5 x 109/L and platelets greater than or equal to 100 x 109/L at screening) 10. Adequate liver function i.e. plasma bilirubin less than or equal to 1.5 x ULN (upper limit of normal), and ALT and ALP less than or equal to 2.5 x ULN (ALP less than or equal to 5 x ULN in case of liver metastases), at screening 11. Prothrombin time (PT) or International Normalized Ratio (INR) less than or equal to 1.5 12. Serum total calcium and/or phosphate less than or equal to ULN |
| Key exclusion criteria | 1. Being considered for subsequent radical treatment with the possibility of cure 2. Prior treatments with any of the following, prior to first dose of study treatment: 2.1. AZD4547 2.2. Any investigational agents or study drugs from a previous clinical study within 30 days 2.3. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks 2.4. Major surgery within 4 weeks 2.5. Radiotherapy 2.5.1. With a wide field of radiation or involving >30% of total bone marrow volume, within 4 weeks 2.5.2. With a limited field of radiation, for palliation, within 2 weeks 3. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 (with the exception of alopecia) at the time of registration 4. Any of the following pre-existing conditions 4.1. Other malignant disease 4.1.1. Previous malignancy other than non-melanoma skin cancer, cervical carcinoma in situ or incidental localised prostate cancer 4.1.2. Previously-identified central nervous system (CNS) metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment 4.2. Infections: Clinically significant bacterial or fungal infection 4.2.1 Known active viral infection with: human immunodeficiency virus (HIV), hepatitis B or C virus 4.3. Gastro-intestinal: Previous bowel resection or other condition which might preclude adequate absorption of AZD4547 4.4. Other: any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses 5. Any of the following ophthalmological criteria: 5.1. Current evidence or previous history of retinal pigmented epithelium detachment (RPED) 5.2. Previous laser treatment or intra-ocular injection for treatment of macular degeneration 5.3. Current evidence or previous history of dry or wet age-related macular degeneration 5.4. Current evidence or previous history of retinal vein occlusion (RVO) 5.5. Patients with uncontrolled glaucoma or intra-ocular pressure greater than or equal to 21mm Hg at screening. 6. Women who are pregnant or breast feeding - women of child-bearing potential must have a negative pregnancy test performed within 7 days prior to the start of study treatment 7. Men or women who are not prepared to practise methods of contraception of proven efficacy 8. Any patient who, in the judgment of the investigator, is unlikely to comply with study procedures, restrictions or requirements |
| Date of first enrolment | 01/02/2012 |
| Date of final enrolment | 30/09/2016 |
Locations
Countries of recruitment
- United Kingdom
Study participating centres
Southampton Hospitals NHS Trust
Southampton
SO16 6YD
United Kingdom
SO16 6YD
United Kingdom
Clatterbridge Cancer Centre
Wirral
CH63 4JY
United Kingdom
CH63 4JY
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN
United Kingdom
G12 0YN
United Kingdom
St Bart’s Hospital
London
EC1A 7BE
United Kingdom
EC1A 7BE
United Kingdom
Velindre Hospital
Cardiff
CF14 2TL
United Kingdom
CF14 2TL
United Kingdom
St James’ University Hospital
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
Sponsor information
University of Leeds (UK)
University/education
University/education
Department of Research & Development
34 Hyde Terrace
Leeds
LS9 6LN
England
United Kingdom
| Website | http://www.leeds.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/024mrxd33 |
Funders
Funder type
Industry
AstraZeneca (UK)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Cancer Research UK (CRUK) (UK)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | To be confirmed at a later date |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 31/08/2019 | 26/10/2021 | No | No |
Editorial Notes
26/10/2021: The following changes were made to the trial record:
1. The basic results have been added as a link to the EudraCT results summary.
2. The total final enrolment was added.
01/08/2016: the recruitment end date was changed from 31/12/2016 to 30/09/2016.
24/05/2016: the overall trial end date was changed from 30/07/2016 to 01/07/2017.
10/05/2016: the overall trial end date was changed from 01/02/2014 to 30/07/2016.
