Assessing the use of tailored treatments based on combinations of genes that are active in a tumour, and the impact on outcomes for bladder cancer.
- Conditions
- CancerMuscle invasive bladder cancer with pure or mixed urothelial (transitional) cell carcinoma
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 320
Inclusion criteria for registration:
1. Age =18 years
2. Eastern Co-operative Oncology Group (ECOG) performance status 0 or 1
3. Currently considered for neoadjuvant chemotherapy and radical cystectomy with curative intent and suitable for all protocol defined treatment (chemotherapy and immunotherapy as defined for all treatment groups in this protocol)
4. Histological confirmation of MIBC with pure or mixed urothelial (transitional) cell carcinoma (full report not required)
5. Written informed consent for registration (PIS-1 and Participant Supplementary Document)
Inclusion criteria for randomisation:
1. Diagnosed with MIBC staged as either T2-4a N0 M0 or T (any) N1 M0
2. Planned for neoadjuvant chemotherapy and radical cystectomy with curative intent and suitable for all protocol defined treatment (chemotherapy and immunotherapy as defined for all treatment groups in the protocol)
3. Confirmation of a pure or mixed urothelial (transitional cell) carcinoma tumour histology based on local institutional pathology reporting
4. ECOG performance status 0 or 1
5. Estimated glomerular filtration rate of =60 ml/min according to local institutional standard methods for estimation (For patients with impaired GFR (40-60 ml/min) a split dose cisplatin 35 mg/m2 on days 1 and 8 is permitted.)
6. Adequate haematological parameters
6.1. Haemoglobin =90 g/Lb.
6.3 Neutrophil count =1.5 x109 /L
6.2. Platelets =100 x109 /L
7. Adequate biochemical parameters
7.1. Bilirubin =1.5 x ULN unless due to Gilbert’s syndrome
7.2. ALT and/or AST =1.5 x ULN (both ALT and AST are recommended)
8. Body weight >30 kg
9. Life expectancy of at least 12 weeks
10. For women of childbearing potential, negative blood serum pregnancy test and adequate contraceptive precautions
11. For men of reproductive potential, effective contraception if the risk of conception exists
12. Written informed consent for randomisation (PIS-2 and Participant Supplementary Document)
13. Patients must be able and willing to comply with the terms of the protocol
1. Bladder tumour where a gene expression subtype classification cannot be made
2.TURBT sample processing delay such that >4 weeks from receipt of TURBT sample at central lab to receipt of gene expression subtype result at site
3. Known or suspected allergy or hypersensitivity reaction to any of the components of study treatment or their excipients for any of the treatment groups in the protocol
4. Active infection likely to impact safety of treatment delivery for any of the study treatment groups in the protocol or radical cystectomy. This includes known active tuberculosis, hepatitis B (known positive HBsAg result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid
5. Active documented autoimmune or inflammatory disorders, including but not limited to, inflammatory bowel disease (e.g., colitis or Crohn’s disease), systemic lupus erythematosus, sarcoidosis, Wegener syndrome (granulomatosis with polyangiitis), Graves’ disease, rheumatoid arthritis and uveitis. Exceptions: vitiligo, alopecia, hypothyroidism that is stable on hormone replacement and any chronic skin condition not requiring systemic therapy
6. Major surgical procedure <28 days prior to randomisation
7. Coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris or congestive cardiac failure (New York Heart Association > grade 2) within the last 6 months
8. Mean QT interval corrected for heart rate =470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
9. Uncontrolled concurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise ability of the
patient to give written informed consent
10. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in inclusion criteria
11. Current or prior use of immunosuppressive medications within 14 days prior to
randomisation including, but not limited to, systemic corticosteroids at doses exceeding 10 mg /day of prednisolone or equivalent, methotrexate, azathioprine, and tumour necrosis factor-a blockers. Permitted exceptions include: use prior to imaging procedures in patients with contrast allergies, use of inhaled, topical, and intranasal corticosteroids
12. Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
13. A current separate other malignancy. Current non-melanoma skin cancer, cervical carcinoma in situ or incidental localised prostate cancer is permissible. Other prior malignancy is acceptable if treatment within GUSTO is given with curative intent
14. Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable
15. Br
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method