Unresectable Stage IV Urothelial Cancer MedDRA version: 20.0 Level: LLT Classification code 10022880 Term: Invasive bladder cancer stage IV System Organ Class: 100000004864
Conditions
Interventions
Product Name: durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Conce
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated, written ICF 3. 4 2. Histologically or cytologically documented TCC/UC of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) also meeting the following: Unresectable, Stage IV disease; No prior systemic therapy for unresectable, Stage IV disease. 3. Ineligible for cisplatin-based chemotherapy defined as meeting one of the following criteria: CrCl =65 years) yes F.1.3.1 Number of subjects for this age range 192
Exclusion criteria
Exclusion criteria: 1. Active or prior documented autoimmune or inflammatory disorders. 2. Other invasive malignancy within 5 years before the first dose of the IP. 3. Major surgical procedure within 28 days prior to the first dose 4. Brain metastases or spinal cord compression unless the patient’s condition is stable and off steroid for at least 14 days 5. History of active primary immunodeficiency. 6. Active infection including tuberculosis (TB) 7. History of allogenic organ transplantation. 8. Uncontrolled intercurrent illness 9. Prior exposure to a PARP inhibitor or immune-mediated therapy. 10. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. 11. Current or prior use of immunosuppressive medication within 14 days before the first dose of the IP. 12. No radiation therapy is allowed, unless it is (1) definitive radiation that had been administered at least 12 months prior; (2) palliative radiation to the brain, with associated criteria for stability or lack of symptoms; or (3) palliative radiation to painful bony lesions (this must comprise less than 30% of the bone marrow) or symptomatic pelvic soft tissue mass(es). 13. Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP. 14. Patients with a known hypersensitivity to durvalumab, olaparib, or any of the excipients of the products. 15. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of durvalumab + olaparib combination therapy compared with durvalumab + placebo in terms of PFS in the subset of patients with HRR mutation (HRRm);Secondary Objective: Key secondary objective: To assess the efficacy of durvalumab + olaparib combination therapy compared with durvalumab + placebo in the subset of randomized patients with HRRm. Endpoint: OS. Additional secondary objectives: To assess the efficacy of durvalumab + olaparib combination therapy compared with durvalumab + placebo in the subset of randomized patients with HRRm. Endpoint: DoR, ORR, APF6 (patients Alive and Progression Free at 6 months), OS18. To assess the PK of durvalumab and olaparib in both treatment arms To investigate the immunogenicity of durvalumab in both treatment arms To assess disease-related symptoms and HRQoL in patients with UC treated with durvalumab + olaparib combination therapy compared with durvalumab + placebo in the subset of randomized patients with HRRm;Primary end point(s): Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: Patient level: Assessment for treatment will be made every 4 weeks during the treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Main secondary end point is: OS (overall survival) Other secondary efficacy endpoints include: Duration of response (DoR) Objective Response Rate (ORR) Progression-free at 6 months (APF6) Patients alive at 18 months (OS18) Concentration of durvalumab and olaparib Presence of anti-drug antibodies (ADA) for durvalumab Patient reported outcome (PRO)including Global health status/QoL, assessed through questionnaire - EORTC QLQ-C30;Timepoint(s) of evaluation of this end point: OS (overall survival) and OS18 Assessment every month until 4 months post-treatment discontinuation; every 2 months thereafter. Other secondary endpoints DoR, ORR, and APF6 will be assessed every 8 weeks (±1 week) for the first 48 weeks; then every 12 weeks (±1 week) thereafter until progression. Concentration of durvalumab and olaparib will be assessed three times, in Cycle 1, 2 and 4. Additional assessments at Day 30 post last dose for olaparib, 3 months post last dose for durvalumab. ADA for durvalumab will be assessed three times, in Cycle 1, 2 and 4, and 3 and 6 months post last dose of durvalumab. PRO:Global health status assessment on day of first dose and every 4 weeks until 3 months post treatment discontinuation. | — |
Countries
Spain
Contacts
Public ContactUnidad de Investigación Clínica
AstraZeneca Farmacéutica Spain, S.A.
Outcome results
None listed