Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer

Conditions

• Muscle Invasive Bladder Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - 130 Years

Healthy Volunteers

Not accepted

Interventions

• AZD4547 — DRUG
  AZD4547 Monotherapy vs. MEDI4736 (durvalumab) + AZD4547 1:1 Randomization.
• MEDI4736 — DRUG
  MEDI4736
• Olaparib — DRUG
  MEDI4736 (durvalumab) + Olaparib
• AZD1775 — DRUG
  MEDI4736 (durvalumab) + AZD1775
• Vistusertib — DRUG
  MEDI4736 (durvalumab) + Vistusertib
• AZD9150 — DRUG
  MEDI4736 (durvalumab) + AZD9150
• Selumetinib — DRUG
  MEDI4736 (durvalumab) + Selumetinib

Study Details

This is an open label, multi-drug, biomarker-directed, multi-centre, multi-arm, Phase 1b study in patients with muscle invasive bladder cancer (MIBC) (urothelial) who have progressed on prior treatment. This study is modular in design, allowing evaluation of the safety, tolerability, pharmacokinetics and anti-tumour activity of multiple agents as monotherapy and as combinations of different novel anti-cancer agents. The study will consist of a number of study modules (sub-studies), each evaluating the safety and tolerability of a specific agent or combination.

Key Dates

Start date

Dec 28, 2016

Status verified

Dec 2025

Primary completion

Mar 18, 2020

Completion

Jan 30, 2026

Study Design

Enrollment

117 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Module A: AZD4547 Monotherapy
  AZD4547 will be given orally twice daily until disease progression. Patients who receive AZD4547 as monotherapy will have the option to cross over to durvalumab as monotherapy at the point of objective progression, as long as the following criteria are met: * The investigator believes it is in the patient's interest to receive durvalumab; * The patient consents to the continued treatment; * It is clinically appropriate for the patient to continue on durvalumab treatment; * The patient satisfies the key eligibility criteria for receiving durvalumab treatment.
• Experimental: Module A: MEDI4736 (durvalumab) + AZD4547
  AZD4547 will be given orally twice daily until disease progression. Patients will also receive MEDI 4736 (durvalumab) by IV infusion once every 4 weeks.
• Experimental: Module B: MEDI4736 (durvalumab) + Olaparib
  MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Olaparib will be given orally twice daily.
• Experimental: Module C: MEDI4736 (durvaluamb) + AZD1775
  MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. AZD1775 will be given orally in approximate 12 hour intervals over 3 days (6 doses) on Days 1-3, 8-10, and 15-17 of 28 day cycles.
• Experimental: Module D: MEDI4736 (durvalumab) monotherapy
  MEDI 4736 (durvalumab) will be given by IV infusion once every 4 weeks.
• Experimental: Module E: MEDI4736 (durvalumab) + Vistusertib
  MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Vistusertib will be given orally twice per day on an intermittent schedule (2 days on, 5 days off).
• Experimental: Module F: MEDI4736 (durvaluamb) + AZD9150
  AZD9150 will be given as monotherapy on Days -7, -5, and -3 of a one week lead-in period. Combination dosing with IV AZD9150 followed by IV MEDI4736 (durvalumab) begins on Day 1 of each 28 day cycle. Thereafter AZD9150 is given weekly and MEDI4736 is given once every 4 weeks.
• Experimental: Module G: MEDI4736 + Selumetinib

Primary Outcome Measure

Module A: The frequency and nature of adverse events related to AZD4547 monotherapy. [ Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly. ]

Locations (8)

Find similar trials in Los Angeles, CA

Related Studies

• Sample Collection for Ongoing Research and Product Evaluation Study
  Recruiting · Natera, Inc. · Austin, Texas