A clinical trial of a Tailored ImmunoTherapy Approach with Nivolumab in subjects with metastatic or advanced Transitional Cell Carcinoma

Phase 1

• Conditions: subjects in untreated (1st line*) and platinum-based pretreated (2nd and 3rd line) subjects with metastatic or surgically unresectable TCC*First-line has been finally stopped since 06.01.2020; MedDRA version: 21.0Level: LLTClassification code 10038514Term: Renal pelvis and ureteric cancer transitional cell metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10071664Term: Bladder transitional cell carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10038509Term: Renal pelvis and ureteric cancer metastatic transitional cellSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10044423Term: Transitional cell carcinoma ureter metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10044406Term: Transitional cell cancer of renal pelvis and ureter metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10038498Term: Renal pelvis and ureter transitional cell cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10026427Term: Malignant neoplasm of renal pelvis and ureter localized transitional cellSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10066752Term: Bladder transitional cell carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004857-33-AT
• Lead Sponsor: AIO-Studien-gGmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-09-04
• Last Update Posted: 23 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

•Signed Written Informed Consent
a)Subjects or legally acceptable representatives must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
b)Subjects or legally acceptable representatives must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
•Target population:
c)Histological evidence of metastatic or surgically unresectable transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis. Minor histologic variants of transitional cell carcinoma (e.g. squamous cell, comprising <50 % of the tumor) are acceptable.
d)Subjects must have advanced or surgically unresectable TCC (cT4b, any N or any T, N2-N3 or any M1) without prior systemic therapy (1st line cohort*) or having progressed during or after platinum-based first line therapy and up to 1 further treatment line (2nd and 3rd line cohort). Subjects, who have received neoadjuvant or adjuvant cisplatin based chemotherapy are eligible and considered first line provided that progression has occurred >12 months from last therapy [for chemoradiation and adjuvant treatment] or >12 months from last surgery [for neoadjuvant treatment]; in all other patients who received cisplatin based neoadjuvant and/or adjuvant chemotherapy and progression within 12 months this will be considered one line of therapy.
*First-line has been finally stopped since 06.01.2020
e)KPS of at least 70%
f)Measurable disease as per RECIST v1.1
g)Formalin-fixed paraffin embedded tumor tissue obtained within 2 years prior to screening must be available and received by the central pathology (tumor block is preferred, alternatively 15 unstained slides). Note that:
i.Fine Needle Aspiration [FNA] and bone metastases samples (without soft tissue component) are not acceptable for submission).
ii.Tumor lesions used for newly acquired biopsies should not be target lesions, unless there are no other lesions.
•Age and Reproductive Status
h)Males and Females, ? 18 years of age
i)Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
j)Women must not be breastfeeding
k)Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for a period of 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo five half lives. The terminal half lives of nivolumab and ipilimumab are up to 25 days and 18 days, respectively. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
l)Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a period of 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo five half lives. The terminal half lives of nivolumab and ipilimumab are up to 25 days and 18 days, respectively. Males who receive nivolumab combined with ipilimumab who are sexually active with WOCBP must continue contraception for 31 weeks (90 days plus the time require

Exclusion Criteria

•Target Disease Exceptions
a)Any history of or current CNS metastases. Baseline imaging of the brain by MRI (preferred) or CT scan is required within 28 days prior to registration in 2nd/3rd line patients only.
•Medical History and Concurrent Diseases
b)Prior systemic treatment with more than two different chemotherapy regimen (Sequential chemotherapy as a planned sequence to optimize response will count as 1 regimen)
c)Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti CTLA 4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
d)Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
e)Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
f)Prior malignancy active within the previous 3 years except for
i.locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
ii.Patients in active surveillance for prostate cancer
g)Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
h)Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection.
i)Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator’s opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
j)Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study drug.
k)Anti-cancer therapy less than 28 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug.
l)Presence of any toxicities attributed to prior anti-cancer therapy other than neuropathy, alopecia and fatigue, that have not resolved to Grade 1 (NCI CTCAE v4) or baseline before administration of study drug.
•Physical and Laboratory Test Findings
m)Any of the following laboratory test findings:
i.WBC < 2,000/mm3
ii.Neutrophils < 1,500/mm3
iii.Platelets < 100,000/mm3
iv.AST or ALT > 3 x ULN (> 5 x ULN if liver metastases are present)
v.Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
vi.Serum creatinine > 1.5 x upper limit of normal (ULN) or creatinine clearance < 40 mL/min (measured or calculated by Cockroft-Gault formula):
•Allergies and Adverse Drug Reaction
n)History of severe hypersensitivity reaction to any monoclonal antibody or any constituent of the products.
•Other Exclusion Criteria
o)Prisoners or subjects who are involuntarily incarcerated
p)Subjects who are compu

Study & Design

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