Condition category
Cancer
Date applied
24/08/2011
Date assigned
14/10/2011
Last edited
01/08/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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 measures

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

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

http://www.leeds.ac.uk/

Funders

Funder type

Industry

Funder name

AstraZeneca (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

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

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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.