Efficacy of Atezolizumab Concurrent with Radiotherapy in Patients with Muscle-Invasive Bladder Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Grupo Espanol De Oncologia Genitourinaria-Socug

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Sep 2019 → ongoing

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514604-14-00

EudraCT number

2018-004348-47

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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 11

1. To evaluate overall survival (OS).
2. To evaluate disease specific survival (DSS).
3. To evaluate disease free survival (DFS).
4. To evaluate bladder intact disease-free survival (BIDFS).
5. To calculate the number of patients with muscle invasive and non-muscle invasive local failure (LF).
6. To determine the rate of distance metastases defined as the percentage of patients who develop metastases.
7. To determine to the rate of patients with bladder preserved.
8. To determine to the rate of immediate or late salvage cystectomy.
9. The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy.
10. 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.
11. The correlation between the levels of IFN-γ, 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.

Conditions and MedDRA coding

Muscle-invasive bladder cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 who refuse treatment with cisplatin-based chemotherapy or in whom treatment with cisplatin-based therapy is not appropriate.
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. 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).
9. 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).
10. 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.
11. 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.
12. 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.
13. A paraffin-embedded tumour sample must be available for the associate molecular study.

Exclusion criteria 16

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). Tumours measures must be done post-TUR via CT scan.
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be the pathological complete response defined as a response of grade 5 according to Miller and Payne criteria (Appendix 5) after the end of the treatment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Grupo Espanol De Oncologia Genitourinaria-Socug

Sponsor organisation

Grupo Espanol De Oncologia Genitourinaria-Socug

Address

Calle De Velazquez 7 Floor 3

City

Madrid

Postcode

28001

Country

Spain

Scientific contact point

Organisation

Grupo Espanol De Oncologia Genitourinaria-Socug

Contact name

Isabel Grau

Public contact point

Organisation

Grupo Espanol De Oncologia Genitourinaria-Socug

Contact name

Isabel Grau

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications