A phase II study investigating use of the drug MPDL3280A before surgery in patients with rare subtypes of bladdercancer and urinary cancers

Phase 1

Conditions: Tumours of the urothelial tract requiring surgery (T1 high grade-T4a of the bladder, rare histological subtypes) and upper urinary tract (high grade or high risk)
MedDRA version: 20.0Level: LLTClassification code 10046384Term: Ureteral cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10026426Term: Malignant neoplasm of renal pelvisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2019-004628-39-ES

Lead Sponsor: Queen Mary University of London

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 58

Inclusion Criteria

1. Willing and able to provide written informed consent
2. Ability to comply with the protocol
3. Age = 18 years
4. Residual disease after TURBT or ureteroscopy (surgical opinion, cystoscopy/ ureteroscopy or radiological evidence).
5. Fit and planned for cystectomy or radical surgery of the upper tract (according to local guidelines).
6. N0 or M0 disease CT or MRI (within 4 weeks of registration)
7. Representative formalin-fixed paraffin embedded (FFPE) tumour samples with an associated pathology report that are determined to be available and sufficient for central testing.
8. Patients who refuse neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
10. Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
11. For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 5 months after the last dose of atezolizumab.
12. Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment defined by the following:
a. ANC = 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
b. WBC counts > 2500/µL
c. Lymphocyte count = 500/µL
d. Platelet count = 100,000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
e. Haemoglobin = 9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion).
f. AST or ALT and alkaline phosphatase = 2.5 times the institutional upper limit of normal (ULN) and serum bilirubin level = 1.5 times the institutional ULN (patients with known Gilbert disease who have serum bilirubin level = 3 × the institutional ULN may be enrolled)
g. INR and aPTT = 1.5 × the institutional ULN. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
h. Calculated creatinine clearance = 20 mL/min (Cockcroft-Gault formula)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

1. Pregnant and lactating female patients.
2. Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
3. Previously intravenous chemotherapy for urothelial cancer.
4. Patients with prior allogeneic stem cell or solid organ transplantation.
5. Prior treatment with CD137 agonists, anti-CTLA-4, anti PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
6. Patients must not have had oral or IV steroids for 14 days prior to study entry. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
7. Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible).
8. Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study.
9. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
10. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrolment.
11. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease.
12. Malignancies other than Urothelial Carcinoma within 5 years prior to Cycle 1, Day 1.
13. Severe infections within 4 weeks prior to enrolment in the study.
14. Significant cardiovascular disease,.
15. History of idiopathic pulmonary fibrosis.
16. Patients with uncontrolled Type 1 diabetes mellitus.
17. Patients with active hepatitis infection.
18. Positive test for HIV.
19. Patients with active tuberculosis
20. History of gastrointestinal disorders which may interfere with the absorption of the study drug.
21. Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
22. History of autoimmune disease
23. Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
24. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
25. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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