Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr John Chester
ORCID ID
Contact details
Clinical Trials Research Unit
University of Leeds
Leeds
LS2 9JT
United Kingdom
-
medctfst@leeds.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
MO11/9803
Study information
Scientific title
Fibroblast growth factor receptors (FGFR) Inhibition for Epithelial Solid Tumours: a phase Ib trial of AZD4547 in combination with gemcitabine and cisplatin
Acronym
FIESTA
Study hypothesis
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
Not provided at time of registration
Study design
Dose escalation cohort trial followed by a randomised expansion cohort
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Phase I
Drug names
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 trial start date
01/02/2012
Overall trial end date
01/07/2017
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
44
Participant 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
Recruitment start date
01/02/2012
Recruitment end date
30/09/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Southampton Hospitals NHS Trust
Southampton
SO16 6YD
Trial participating centre
Clatterbridge Cancer Centre
Wirral
CH63 4JY
Trial participating centre
Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN
Trial participating centre
St Bart’s Hospital
London
EC1A 7BE
Trial participating centre
Velindre Hospital
Cardiff
CF14 2TL
Trial participating centre
St James’ University Hospital
Leeds
LS9 7TF
Sponsor information
Organisation
University of Leeds (UK)
Sponsor details
Department of Research & Development
34 Hyde Terrace
Leeds
LS9 6LN
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
AstraZeneca (UK)
Alternative name(s)
AstraZeneca PLC
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United Kingdom
Funder name
Cancer Research UK (CRUK) (UK)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list