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Clinical Trial 19616

Cancer Type: Genitourinary
Interventions:

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Jingsong Zhang

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Platinum-Ineligible Patients With Unresectable Stage IV Urothelial Cancer

Summary

Objective

Primary objective: To assess the efficacy of durvalumab + olaparib combination therapy compared with durvalumab + placebo in terms of PFS in the subset of patients with HRRm Endpoint/Variable:PFS as determined by Investigator assessment according to RECIST 1.1 Secondary objectives: 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/Variable: 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,DoR, ORR, and APF6 according to RECIST 1.1 using Investigator assessment OS18 To assess the PK of durvalumab and olaparib in both treatment arms Concentration of durvalumab and olaparib To investigate the immunogenicity of durvalumab in both treatment arms Presence of ADAs for durvalumab 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 EORTC QLQ-C30: Global health status/QoL, functioning (physical), and multi-term symptoms (fatigue and pain) Safety objective: Endpoint/Variable: To assess the safety and tolerability profile of durvalumab + olaparib combination therapy compared with durvalumab + placebo in both the subset of HRRm patients and the full study population AEs/SAEs, physical examinations, laboratory findings (including clinical chemistry, hematology and urinalysis), WHO/ECOG performance status, and vital signs Exploratory objectives Endpoint/Variable: To assess the efficacy of durvalumab + olaparib combination therapy compared with durvalumab + placebo in the subset of randomized patients with HRRwt, PFS, ORR, DoR, APF6, OS, and OS18 To estimate the efficacy of durvalumab + olaparib combination therapy compared with durvalumab + placebo in the all comers population (HRRm and HRRwt combined) PFS 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 HRRwt EORTC QLQ-C30: Global health status/QoL, functioning (physical), and multi-term symptoms (fatigue and pain) To assess overall change in health status since the start of study treatment in UC patients treated with durvalumab + olaparib combination therapy compared with durvalumab + placebo PGIC To explore the impact of treatment and disease state on health state utility using the EQ-5D-5L during assigned treatment EQ-5D-5L index will be used to derive health state utility based on patient-reported data To collect blood and tissue samples for defining biological responses to durvalumab + olaparib and for identifying candidate markers that may correlate with likelihood of clinical benefit Biomarkers (eg, DNA or ctDNA alterations, protein expression detected by IHC, change in ctDNA levels, and mRNA expression) correlating with clinical response

Inclusion Criteria

  • Provision of signed and dated, written ICF
  • 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.
  • Ineligible for platinum-based chemotherapy defined as (i) in the opinion of the Investigator, unfit for carboplatin-based chemotherapy and (ii) meeting one of the following criteria: CrCl > Known tumor HRR mutation status prior to randomization.
  • World Health Organization (WHO)/ECOG performance status of 0, 1, or 2.
  • Patients with at least 1 RECIST 1.1 target lesion at baseline.
  • Ability to swallow oral medications.
  • Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

  • Exclusion Criteria

  • Active or prior documented autoimmune or inflammatory disorders.
  • Other invasive malignancy within 5 years before the first dose of the IP.
  • Major surgical procedure within 28 days prior to the first dose
  • Brain metastases or spinal cord compression unless the patient's condition is stable and off steroid for at least 14 days
  • History of active primary immunodeficiency.
  • Active infection including tuberculosis (TB)
  • History of allogenic organ transplantation.
  • Uncontrolled intercurrent illness
  • Prior exposure to a PARP inhibitor or immune-mediated therapy.
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of the IP.
  • 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).
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP.
  • Patients with a known hypersensitivity to durvalumab, olaparib, or any of the excipients of the products.
  • 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.