Phase I Study of AZD5363 + Olaparib + Durvalumab in Patients With Advanced or Metastatic Solid Tumor Malignancies

Sponsor
National University Hospital, Singapore
Study ID
NCT03772561
Phase
PHASE1
Status
Recruiting
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Conditions

  • Solid Tumor, Adult

Eligibility Criteria

Sex
ALL
Age
21 Years - 99 Years
Healthy Volunteers
Not accepted

Interventions

  • AZD5363+Olaparib+Durvalumab — DRUG
    Patients will receive AZD5363 orally twice a day 4 days-on/ 3 days-off starting 14 days prior to cycle 1 day 1 (C1D1). Olaparib continuously twice a day at 300mg and Durvalumab intravenously at 1500mg once every 4 weeks will commence at C1D1. Treatment will continue until disease progression or the development of unacceptable toxicities.

Study Details

This is a Phase 1 dose-escalation study to evaluate the safety and tolerability of combination treatment of AZD5363 + Olaparib + Durvalumab and to determine the RP2D in patients with advanced or metastatic solid tumor malignancies. The purpose of this trial is to determine if combination treatment of drugs, Olaparib, AZD5363 and Durvalumab has beneficial effects in advanced or metastatic cancers and to determine the effects it has on patients and their cancer. Primary Objectives • To evaluate the safety and tolerability of combination treatment AZD5363 + Olaparib + Durvalumab and determine the Maximum Tolerated Dose (MTD), Dose-Limiting Toxicities (DLTs), and Recommended Phase 2 Dose (RP2D) for patients with advanced or metastatic solid tumor malignancies. Secondary Objectives * To determine the pharmacodynamics (PDn) of combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies * To describe anti-tumor response using immune RECIST of combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies Exploratory Objectives * To evaluate anti-tumour response using RECIST v1.1 for combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies * To explore molecular correlates of the relationship between mutations in Akt/ PIK3CA/PTEN pathway and response to AZD5363 +Olaparib+ Durvalumab * To understand the role of tumour microenvironment in regulation of intratumoral immune regulators (i.e. T-regulatory cells) in improving response to Durvalumab * To understand the role of AZD5363 as an immunomodulator * To evaluate the role of PD-1 and PDL-1 immunohistochemical and tumour MMR status in predicting response to immune check point inhibitors.

Key Dates

Start date
Dec 3, 2018
Status verified
Jul 2025
Primary completion
Dec 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
40 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: AZD5363+Olaparib+Durvalumab
    A traditional 3+3 design will be used during the dose escalation part of the study. Patients will receive AZD5363 orally twice a day 4 days-on/ 3 days-off starting 14 days prior to cycle 1 day 1 (C1D1). Olaparib continuously twice a day at 300mg and Durvalumab intravenously at 1500mg once every 4 weeks will commence at C1D1. Treatment will continue until disease progression or the development of unacceptable toxicities.

Primary Outcome Measure

Objective response rate [ Time Frame: 5 years ]

Central Contacts

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