Muscle invasive bladder cancer MedDRA version: 21.1 Level: LLT Classification code 10022877 Term: Invasive bladder cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Imfinzi
Product Name: Durvalumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Durvalumab
CAS Number: 1428935-60-7
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
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: o Haemoglobin =100 g/L o Absolute neutrophil count 1.5 x 109/L o Platelet count =100 x 109/L o Serum bilirubin =1.5 x institutional upper limit of normal (ULN). o AST or ALT =2.5 x institutional upper limit of normal o Calculated 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 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We hypothesise that the known interaction of chemotherapy and radiotherapy are increased by the addition of further cancer therapies, specifically drugs that block immune system cells, like durvalumab. These drugs may supplement the effect of radiotherapy and chemotherapy in muscle invasive bladder cancer and thus improve local control and the spread of the disease. The aim of RadIO is therefore to assess the safety, feasibility and efficacy of a combination of radiotherapy with durvalumab and chemotherapy in muscle invasive bladder cancer using a randomised multi-arm multi-stage design. ;Secondary Objective: The patient experience during treatment is also important to describe in Rad-IO. A standard quality of life evaluation will therefore be performed. ;Primary end point(s): Stage 1: Safety - Adverse Events (AEs) will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Acute toxicity defined as related AEs experienced during treatment and late toxicity defined as related AEs reported at a time more than three month’s from completion of treatment. The number of patients experiencing each event will be reported by type and severity. Stage 2: Disease-free survival time - Defined as the number of whole days between the date of randomisation and the earliest date of • Diagnosis of distant metastases • Diagnosis of loco-regional nodal disease • Diagnosis of new muscle invasive tumour in the bladder • Diagnosis of non-muscle invasive tumour in the bladder • Diagnosis of upper tract urothelial cancer • Death from bladder cancer Stage 3: Overall survival time - defined as the number of whole days between the date of randomisation and date of death from any cause. Patients who do not die during the course of the trial will be censored at the last date of assessment. ;Timepoint(s) of evaluation of this end point: Stage 1 (Pilot): The first 6 patients in the Research Arm will be evaluated for feasibility and safet | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Stage 1: Feasibility - defined as the impact on radiotherapy treatment and assessed by days delay to start of radiotherapy, days extension in length of planned radiotherapy and stopping radiotherapy early. Stage 2: Toxicity - will be graded as per the safety outcome in the pilot stage. Rate of occurrences of AEs of Grade 3 or higher will be reported along with all Adverse Events of Special Interest (AESI). Delivery of core target therapy (chemoradiotherapy)- defined as the impact on radiotherapy treatment and assessed by days delay to start of radiotherapy, days extension in length of planned radiotherapy and stopping radiotherapy early. Time to local muscle invasive progression - defined as the number of whole days between the date of randomisation and the date of detection of local muscle invasive bladder cancer or death from bladder cancer, whichever occurs first. Patients with no evidence of local muscle invasive disease will be censored at the last date of assessment or date of death if death is not attributed to bladder cancer. Time to local non-muscle invasive progression - defined as the number of whole days between the date of randomisation and the date of detection of local non-muscle invasive bladder cancer or death from bladder cancer, whichever occurs first. Patients with no evidence of local non-muscle invasive disease will be censored at the last date of assessment or date of death if death is not attributed to bladder cancer. Time to regional nodal progression - defined as the number of whole days between the date of randomisation and the date of detection of loco-regional recurrence in lymph nodes within the true pelvis or death from bladder cancer, whichever occurs first. Patients with no evidence of regional nodal disease will be censored at the last date of assessment or date of death if death is not attributed to bladder cancer. Time to local progression - defined as the number of whole days between the date of | — |
Countries
United Kingdom
Contacts
Public ContactAna Hughes
University of Birmingham
Outcome results
None listed