An investigational immunotherapy study of Nivolumab combined with chemoradiotherapy , compared to chemoradiotherapy by itself, in patients with bladder cancer, not undergoing cystectomy

Phase 1

• Conditions: MedDRA version: 20.0 Level: PT Classification code 10005003 Term: Bladder cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); muscle-invasive bladder cancer (MIBC); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003447-34-GR
• Lead Sponsor: Hellenic Genitourinary Cancer Group (HGUCG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-26
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 78

Inclusion Criteria

1. Histologically confirmed bladder carcinoma with invasion of muscularis propria.
2. Urothelial, squamous and glandular histological subtypes are acceptable
3. Clinical stage cT2-T4a; N0, M0according to the 8th edition of the American Joint Committee on Cancer (AJCC), (Appendix III)
4. Patients must be judged to be medically inappropriate for radical cystectomy or patients who refuse radical cystectomy.
5. Age 18 years.
6. Performance status ? 1 based on the ECOG (Eastern Cooperative Oncology Group) scale (Appendix II).
7. Patients must have undergone a vigorous TURB by an urologist. Bimanual evaluation and tumor mapping prior to enrollment as specified in Lipiodol labeled to the tumor bed by the urologist during TURB is advised but is not mandatory for enrollment (Appendix IV).
8. Protocol treatment should begin within 3 to 8 weeks of the most recent TURB.
9. Chest/Abdominal/ pelvic computed tomography (CT) scan and/or magnetic resonance imaging (MRI) scan within 8 weeks prior to randomization.
10. Bone scan and brain imaging should be performed within 28 days prior to randomization in the case of clinical suspicion of bone or brain metastases to rule out metastatic disease prior to enrollment on study.
11. Adequate hematologic, renal, and liver function (using CTCAE v4). (All baseline laboratory requirements will be assessed and should be obtained within 14 days prior to randomization)
a. WBC 2000/µL
b. Neutrophils 1500/µL
c. Platelets 100 x 103/µL
d. Hemoglobin 9.0 g/dL
e. Creatinine clearance (CrCl) 40 mL/min (using the Cockcroft-Gault formula)
f. AST 3 x ULN
g. ALT 3 x ULN
h. Total Bilirubin 1.5 x ULN (except in subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
12. Patients must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy by the joint agreement of the participating radiation oncologist and medical oncologist.
13. Patient must sign a study-specific informed consent prior to study entry.
14. Age and Reproductive Status
a. Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity25 IU/L or equivalent units of beta-human chorionic gonadotropin [HCG]) within24 hours prior to the start of study drug.
b. Women must not be breastfeeding
c. WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug(s) plus 5 months posttreatment completion.
d. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 7 months post-treatment completion.
e. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as described in these sections.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 y

Exclusion Criteria

1.Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, prostate cancer with evidence of undetectable Prostate Specific Antigen (PSA) or carcinoma in situ of the prostate, cervix or breast.
2.Previous systemic chemotherapy or prior biologic agents within 4 weeks, or intravesical Bacillus Calmette-Guerin (BCG) within 6 weeks of the first dose of study treatment.
3.Prior treatment with any PD-1 or PDL-1 inhibitor or anti CTLA4 agent
4.Previous pelvic radiation therapy.
5.Patients with inherited syndromes associated with hypersensitivity to ionizing radiation (e.g., ataxia-telangiectasia, Nijmegen breakage syndrome).
6.Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
7.Any history of inflammatory bowel disease
8.History of abdominal fistula
9. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
10.Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
11.Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus (ribonucleic acid or HCV antibody) indicating acute or chronic infection prior to randomization.
12.Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) prior to randomization.
13.Allergies and Adverse Drug Reaction
a) History of allergy to study drug components.
b) History of severe hypersensitivity reaction to any monoclonal antibody
14.Pregnant or nursing women; this exclusion is necessary because treatment involves unforeseeable risks to the participant and to the embryo or fetus.
15.Men or women of childbearing potential who are sexually active and are not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic

Study & Design

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