Phase Ib Study to Determine MTD of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours.

Ovarian Cancer Clinical Trial

Official title: A Phase Ib Study to Determine the Maximum Tolerated Dose (MTD) of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours.

Status Completed

Clinical Trial Summary

This Phase Ib study will identify the Maximum Tolerated Dose (MTD) of AZD1775 monotherapy when administered orally once daily (QD) or two times per day (BID) on Days 1 to 5 followed by 9 days of rest in 14-day cycles, or QD on a 5/2 dosing schedule (5 days on, followed by 2 days rest) in 21-day cycles in patients with locally advanced or metastatic solid tumours. Alternative treatment schedules may be explored if preliminary data suggest these would be more appropriate.

The effect of food on single dose PK of AZD1775 will be assessed in 12 patients. In this sub-study, patients will receive a single oral dose of AZD1775 with 240 mL of water, once in the fasted state and once following a high-fat meal.

Clinical Trial Description

This study will attempt to determine the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of AZD1775 monotherapy when administered orally once daily (QD) or two times per day (BID) on Days 1 to 5 followed by 9 days of rest in 14-day cycles, or QD on a 5/2 dosing schedule (5 days on, followed by 2 days rest) in 21-day cycles in patients with locally advanced or metastatic solid tumours. Both the QD 5/9 and 5/2 dosing schedules will run in parallel. An evaluation will be made after the second QD cohort has been completed to determine whether to proceed with one or both dosing schedules.

The AZD1775 MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a Dose-Limiting Toxicity (DLT); escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a DLT, 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD. Up to 6 patients will be enrolled in each cohort. Dose escalation will continue until identification of the MTD or Sponsor termination of the study.

A maximum of 10 dose escalations are anticipated in the determination of MTD. Approximately 6 subjects may be added to replace non-evaluable patients. Therefore, a total of 66 patients are expected to be treated.

Dose-limiting toxicities will be evaluated during Cycles 1 and 2 of treatment. If appropriate the DLT observation period can be expanded by up to 2 weeks in case of treatment delay due to study drug-related adverse events. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Patients must complete Cycle 1 and Cycle 2 safety evaluations which will conclude on Cycle 3 Day 1, and must receive at least 80% of the planned dose to be considered evaluable. Patients receiving less than 80% of Cycle 1 and Cycle 2 dose (28 days) will be replaced unless they experienced a confirmed DLT.

The patient population used to determine the MTD will consist of patients who have met the minimum safety evaluation requirements of the study, and/or who have experienced a DLT in Cycle 1 or Cycle 2. Minimum safety requirements will be met if during Cycle 1 and Cycle 2 of treatment the patient receives a minimum of 80% of treatment doses of AZD1775, completes the safety evaluations, and is observed for at least 28 days. Patients who do not meet these minimum safety evaluation and treatment requirements and whom do not experience a DLT will be replaced.

Patients will be allowed to continue treatment with AZD1775 until evidence of disease progression, unacceptable toxicity, or other discontinuation criterion has occurred. ;

Related Conditions & MeSH terms

• Locally Advanced Solid Tumours
• Metastatic Solid Tumours
• Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms

• NCT number: NCT02610075
• Study type: Interventional
• Source: AstraZeneca
• Status: Completed
• Phase: Phase 1
• Start date: December 1, 2015
• Completion date: April 26, 2018