Rad-IO

Phase 1

• Conditions: Muscle invasive bladder cancer; MedDRA version: 21.1Level: LLTClassification code 10022877Term: Invasive bladder cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003520-37-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-22
• Last Update Posted: 23 March 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 159

Inclusion Criteria

•Age >18 years old
• Body weight >30 kg
•Histologically proven invasive bladder carcinoma (adenocarcinoma,
transitional cell carcinoma or squamous cell carcinoma)
•Localised muscle invasive carcinoma either surgically or by imaging (T2-
T4a N0 M0)
•World Health Organisation (WHO) performance status grade 0 to 1
•Adequate normal organ and marrow function as defined below:
oHaemoglobin =100 g/L
oAbsolute neutrophil count 1.5 x 109/L
oPlatelet count =100 x 109/L
oSerum bilirubin =1.5 x institutional upper limit of normal (ULN).
oAST or ALT =2.5 x institutional upper limit of normal
oCalculated creatinine clearance >40 mL/min by the Cockcroft-Gault
formula.
•Available for long-term follow-up
•Fit for a radical course of radiotherapy
•Must have a life expectancy of at least 12 weeks
•Evidence of post-menopausal status or negative urinary or serum pregnancy
test for female pre-menopausal patients. Women will be considered post-
menopausal if they have been amenorrheic for 12 months without an
alternative medical cause. The following age-specific requirements apply:
o Women <50 years of age would be considered post-menopausal if
they have been amenorrheic for 12 months or more following cessation
of exogenous hormonal treatments and if they have luteinizing hormone
and follicle-stimulating hormone levels in the post-menopausal range
for the institution or underwent surgical sterilization (bilateral
oophorectomy or hysterectomy).
o Women =50 years of age would be considered post-menopausal if they
have been amenorrheic for 12 months or more following cessation of all
exogenous hormonal treatments, had radiation-induced menopause with
last menses >1 year ago, had chemotherapy-induced menopause with last
menses >1 year ago, or underwent surgical sterilization (bilateral
oophorectomy, bilateral salpingectomy or hysterectomy).
•Male and female patients of childbearing age willing to use highly
effective contraception
•Patient is willing and able to comply with the protocol for the duration
of the trial including undergoing treatment and scheduled visits and
examinations including follow up.
•Written informed consent and any locally-required authorization obtained
from the patient prior to performing any protocol-related procedures,
including screening evaluations

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 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 133

Exclusion Criteria

•Uncontrolled systemic disease which would preclude the patient from
participating in the trial including severe or uncontrolled
cardiovascular disease
•Restrictive or obstructive disturbances to pulmonary ventilation, renal function or liver function
•Previous pelvic radiotherapy
•Bilateral hip replacements compromising accurate radiotherapy planning
•Evidence of significant clinical disorder, or laboratory finding which,
in the opinion of the investigator, makes it undesirable for the patient
to participate in the trial
•Widespread Carcinoma in situ (CIS), or CIS remote from the muscle
invasive tumour
•Untreated hydronephrosis. Patients with hydronephrosis can be included if
the kidney/ureter has been stented or nephrostomy has been inserted
•Prior participation in another trial (within the previous 30 days) or
concurrent enrolment in another clinical trial, unless it is an
observational (non-interventional) clinical study or during the follow-up
period of an interventional study
•Any unresolved toxicity Common Terminology Criteria for Adverse Events
(CTCAE) Grade =2 from previous anticancer therapy
with the exception of alopecia, vitiligo, and the laboratory values
defined in the inclusion criteria (see protocol for exceptions)
•Any previous treatment with a PD-L or PD-L1 inhibitor, including
durvalumab
•Current or prior use of immunosuppressive medication within 14 days prior
to randomisation, with the exceptions of intranasal and inhaled
corticosteroids or systemic corticosteroids at physiological doses, which
are not to exceed 10 mg/day of prednisone, or an equivalent
corticosteroid (see protocol for exceptions)
•Current use of brivudin, sorivudin, and analogues
•Patients with an active non-infective pneumonitis
•History of primary immunodeficiency
•Known history of previous clinical diagnosis of tuberculosis (TB)
•Any concurrent chemotherapy, Investigational Medicinal Product,
biologic, or hormonal therapy for cancer treatment. Concurrent use of
hormonal therapy for non-cancer-related conditions is acceptable.
•Major surgical procedure other than transurethral resection of the
bladder tumour within 30 days prior to randomisation
•History of allogenic organ transplantation
•Active or prior documented autoimmune or inflammatory disorders (see
protocol for exceptions).
•Uncontrolled intercurrent illness (see protocol for details)
•History of another primary malignancy (see protocol for details)
• Metastatic disease
•Acute, serious (e.g. Herpes zoster, chickenpox) or active infection
including TB, hepatitis B (known positive Hepatitis B, Hepatitis C, or
HIV
•Bone marrow depression after radiotherapy or treatment with other
antineoplastic agents
•Pancytopenia or isolated leucopoenia/thrombopenia or haemorrhagic
diathesis
•Receipt of live attenuated vaccine within 30 days prior to randomisation
•Serious liver impairment
•Homozygotic for diydropyrimidine or known complete absence of
dihydrophyrimidine dehydrogenase (DPD) activity
•Patients undergoing management for non-malignant disease
•Female patients who are breastfeeding
•Known allergy or hypersensitivity to any of the trial IMPs or any of the
trial drug excipients
•Judgement by the Investigator that

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified