EFFICACY OF ATEZOLIZUMAB COMBINED WITH RADIOTHERAPY IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER

Phase 1

• Conditions: MUSCLE-INVASIVE BLADDER CANCER; MedDRA version: 20.0 Level: LLT Classification code 10022877 Term: Invasive bladder cancer System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004348-47-ES
• Lead Sponsor: Grupo Español de Oncología Genitourinaria (SOGUG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-08
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 39

Inclusion Criteria

1.Patients must be 18 years of age or older.
2.Patients have histologically-confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder, in clinical stages T2-4a N0 M0, who are not candidates for radical cystectomy by medical reasons, refusal or patient’s choice.
3.Patients are unfit” to Cisplatin defined as one of the following criteria:
?WHO or ECOG performance status 2 or Karnofsky performance status 60-70%.
?Creatinine clearance (calculated or measured) less than1 mL/s.
?CTCAE version 5, grade 2 or above auditive hearing loss.
?CTCAE version 5, grade 2 or above peripheral neuropathy.
?NYHA class III heart failure.
4.Patients must have ECOG performance status 0 to 2.
5.Patients must have adequate bone marrow function as defined by absolute neutrophil count >1.500/mm3; platelets >100.000/mm3 and HB = 9g/dl.
6.Patients must have adequate renal and liver function as defined by calculated creatinine clearance >15ml/min.
7.Total bilirubin, SGOT (AST) and/or SGPT (ALT) < 2,5 times the upper limit of normal.
8.Patients must have levels of albumin in urine = 25g/dl.
9.International Normalized Ration (INR) or Prothrombin Time (PT): =1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants).
10.Activated Partial Thromboplastin Time (aPTT): =1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants).
11.Female participant of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
12.Female participants of childbearing potential should be willing to use two methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.*
13.Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.*
14.A paraffin-embedded tumour sample must be available for the associate molecular study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

1.Previous treatment with radiotherapy to the bladder, systemic chemotherapy or immune checkpoint inhibitors. Prior intravesical BCG treatment for non-muscle invasive bladder cancer is allowed.
2.Presence of regional lymph node or metastatic extension of the disease.
3.Concurrent treatment with other experimental drugs (within 30 days prior to study entry) or other anti-cancer therapy.
4.History of prior malignancies within the preceding 5 years other than previously treated basal cell carcinoma of the skin, non-muscle invasive bladder cancer, incidental prostate carcinoma Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA <5) and carcinoma in situ of the cervix.
5.Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function.
6.Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.
7.Bulky T3/T4a tumours unsuitable for curative treatment (i.e. > 5 cm in any dimension).
8.Patients with serious uncontrolled infection.
9.Has a known history of active BT (Bacillus Tuberculosis).
10.Has known history of, or any evidence of active, non-infectious pneumonitis.
11.Autoimmune diseases other than vitiligo, type I diabetes mellitus, residual hypothyroidism requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
12.Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid antibody (HCV-Ab) indicating acute or chronic infection.
13.Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
14.Subjects with a condition requiring systemic treatment with either corticosteroids (equivalent to > 10 mg/day prednisone) or other immune-suppressive medications within 14 days of study drug administration.
15.Women of child-bearing potential unwilling to be abstinent or use effective methods of birth control.
16.General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.

Study & Design

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