Fibroblast growth factor receptors (FGFR) Inhibition for Epithelial Solid Tumours

Phase 1

Conditions: Epithelial Solid Tumours. Locally advanced and/or metastatic transitional cell carcinoma (pure or mixed histology) of (upper or lower) urinary tract, including bladder cancer.
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-004072-10-GB

Lead Sponsor: niversity of Leeds

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 28

Inclusion Criteria

Provision of written, informed consent, signed and dated, prior to any trial-specific procedures, sampling or analyses

Age =25 years.

Histologically-confirmed locally advanced/metastatic non-haematological malignancy (a diagnosis based upon cytology is not acceptable).
Dose escalation cohort:
- Any locally-advanced and/or metastatic solid cancer for which gemcitabine and cisplatin is either an accepted standard treatment or for which there is no remaining standard treatment, but gemcitabine and cisplatin with AZD4547 is a reasonable option in the context of a clinical trial. Any number of previous lines of therapy are permitted
- Locally advanced and/or metastatic transitional cell carcinoma of the bladder (or other urinary tract sites), as in the randomised expansion cohort, may be included in the dose escalation cohort
Randomised 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.

Radiologically measurable disease (randomised expansion cohort only)
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.

Minimum life expectancy of 3 months

WHO Performance Status 0-1

Adequate renal function (GFR =60ml/min, measured by isotopic means, uncorrected for surface area)

Adequate bone marrow function (absolute neutrophil count =1.5 x 10^9/L and platelets =100 x 10^9/L)

Adequate liver function i.e. plasma bilirubin =1.5 x ULN, and ALT and ALP =2.5 x ULN (ALP =5 x ULN in case of liver metastases)

Prothrombin time (PT) =1. 5 x ULN or International Normalized Ratio (INR) =1. 5

Serum total calcium and/or phosphate = ULN

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

Being considered for subsequent radical treatment with the possibility of cure

Prior treatments with any of the following, prior to first dose of trial treatment:
a.AZD4547 or any other agent known to inhibit FGFRs
b.Any Investigational Medicinal Products within 30 days
c.Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks
d.Concomitant medications as documented in the protocol and unable to meet any washout periods as required.
e. Major surgery within 4 weeks
f.Radiotherapy
i.with a wide field of radiation or involving >30% of total bone marrow volume, within 4 weeks
ii.with a limited field of radiation, for palliation, within 2 week

Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia) at the time of registration

Any of the following pre-existing conditions:
a.Other malignant disease
i.(Randomised expansion cohort only) Recent or concurrent active malignancy arising from a primary site other than the urinary tract; participants with a history of a separate, treated malignancy, diagnosed 5 or more years previously, can be regarded as cured of their previous tumour, for the purposes of this trial, and may be entered. Current active non-melanoma skin cancer, cervical carcinoma in situ or incidental, localised prostate cancer are also permissible.
b.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 trial treatment.
c.Infections
d.Gastro-intestinal: any condition which might preclude adequate absorption of AZD4547 (e.g. previous small bowel resection)
e.Cardiac: unstable cardiac conditions and risk factors for QTc prolongation.
f.Ophthalmic conditions

History of allergic reactions to any of the drugs used in this trial

Unsuitable to receive cisplatin or gemcitabine

Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses

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 trial treatment

Men or women who are not prepared to practise methods of contraception of proven efficacy

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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