Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer

  • STATUS
    Recruiting
  • End date
    May 7, 2027
  • participants needed
    39
  • sponsor
    Spanish Oncology Genito-Urinary Group
Updated on 20 February 2022
radical cystectomy
cancer
carcinoma
anticoagulants
neutrophil count
aptt
bladder cancer
invasive bladder cancer
atezolizumab
bladder tumor

Summary

Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with localized muscle-invasive bladder cancer treated with a selective multimodality bladder conservative approach.

Description

STUDY DESIGN:

Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with histologically confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder.

The bladder preserving therapy include combined modality therapy with:

STUDY TREATMENTS:

Investigational product (atezolizumab/Tecentriq ):

  • Route of administration: intravenous infusion.
  • Duration of treatment: 16 weeks.
  • Dosage: 1.200 mg intravenous every 3 weeks for a total of 6 doses. Atezolizumab is supplied as atezolizumab 1200 mg/20 mL vials (60 mg/mL) solution for intravenous infusion. After dilution, one mL of solution should contain approximately 4.4 mg of atezolizumab (1,200 mg/270 mL).

External Beam Radiation Therapy (EBRT): radiation

  • Duration of treatment: 6 weeks
  • Dosage: 60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2Gy/day

STUDY POPULATION:

Adult patients (aged 18 years) with histologically confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder, in clinical stages T2-T4a who are not candidates for radical cystectomy by medical reasons, refusal or patients choice.

A total of 39 patients are estimated to be included in the study.

OBJECTIVES

Primary objective:

The primary objective of the study is to determine the efficacy of atezolizumab concurrent with radiotherapy in terms of pathological complete response defined as a response of grade 5 according to Miller and Payne criteria in patients with muscle-invasive bladder cancer treated with bladder preservation intent.

Secondary objectives:

  • To evaluate overall survival (OS).
  • To evaluate disease specific survival (DSS).
  • To evaluate disease free survival (DFS).
  • To evaluate bladder intact disease-free survival (BIDFS).
  • To calculate the number of patients with muscle invasive and non-muscle invasive local failure (LF).
  • To determine the rate of distance metastases defined as the percentage of patients who develop metastases.
  • To determine to the rate of patients with bladder preserved.
  • To determine to the rate of immediate or late salvage cystectomy.
  • The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy.

Exploratory objectives:

  • To determine the predictive role of the expression of PD-1 / PD-L1 and CD8 in terms of pCR, OS and DFS in bladder cancer patients treated with atezolizumab plus radiotherapy.
  • The correlation between the levels of IFN-, interleukin 6 (IL-6), interleukin 18 (IL-18), or ITAC (also called CXCL11 or IP-9) and the efficacy parameters (pCR, OS and DFS) of the treatment with atezolizumab plus radiotherapy.

STUDY VISITS AND PROCEDURES:

The study includes the following visits:

  • Screening: within the 28 days prior to starting the study treatment.
  • Baseline visit: the first day of cycle 1
  • Visits over the treatment period (16 weeks 7 days): from administration of the first dose of the study treatment to the administration of the last dose of atezolizumab or withdrawal from the treatment. Treatment will consist of the administration of atezolizumab at 1,200 mg intravenous every 3 weeks for 6 cycles
  • Post-treatment follow-up: includes the biopsy and safety visit 1-2 months after the last dose of atezolizumab and a subsequent 5 years follow-up period after.
  • End of study visit/ Early termination: In patients who end the study follow-up or prematurely withdraw from the study

Details
Condition Bladder Cancer
Treatment Atezolizumab Injection [Tecentriq], External Beam Radiation Therapy (EBRT)
Clinical Study IdentifierNCT04186013
SponsorSpanish Oncology Genito-Urinary Group
Last Modified on20 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients must be 18 years of age or older
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
Patients who refuse treatment with cisplatin-based chemotherapy or in whom treatment with cisplatin-based therapy is not appropriate
Patients must have ECOG performance status 0 to 2
Patients must have adequate bone marrow function as defined by absolute neutrophil count >1.500/mm3; platelets >100.000/mm3 and HB 9g/dl
Patients must have adequate renal and liver function as defined by calculated creatinine clearance >15ml/min
Total bilirubin, SGOT (AST) and/or SGPT (ALT) < 2,5 times the upper limit of normal
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)
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)
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
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
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 (1)
A paraffin-embedded tumour sample must be available for the associate molecular study

Exclusion Criteria

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
Bulky T3/T4a tumours unsuitable for curative treatment (i.e. > 5 cm in any dimension). Tumours measures must be done post-TUR via CT scan
Presence of regional lymph node or metastatic extension of the disease
Concurrent treatment with other experimental drugs (within 30 days prior to study entry) or other anti-cancer therapy
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
Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function
Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy
Patients with serious uncontrolled infection
Has a known history of active BT (Bacillus Tuberculosis)
Has known history of, or any evidence of active, non-infectious pneumonitis
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
Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid antibody (HCV-Ab) indicating acute or chronic infection
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
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
Women of child-bearing potential unwilling to be abstinent or use effective methods of birth control
General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol
(1) Acceptable methods of effective contraception
Complete sexual abstinence for 14 days before the start of study treatment to 5 months after completion of the investigational treatment
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), or tubal ligation at least six weeks before taking study treatment
Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject
Intrauterine device or system with a documented failure less than 1%
Double barrier method with spermicide
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