An Open-Label, Dose-Escalation Study of AZD2461

An Open-Label, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics fo the PARP Inhibitor AZD2461 in Patients With Refractory Solid Tumors

This study is being conducted to test study drug AZD2461 to see how it may work to treat solid tumors. The main purpose of this study is to determine the safety and tolerability of AZD2461. This is the first time the drug has been given to humans and is classed as a first time in man study. Its main purpose is to establish a safe dosage of the drug and provide additional information on any potential side effects this drug may cause. The study will also assess the blood levels and action of AZD2461 in the body over a period of time and will indicate whether the drug has a therapeutic effect on solid tumors.

Study Overview

• Status: Completed
• Conditions: Refractory Solid Tumors; Cancer Tumor
• Intervention / Treatment: Drug: AZD2461

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with confirmed diagnosis of solid tumor malignancy that is not responsive to standard therapies or for which there is no effective therapy.
• Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1
• Patients must be 18 years of age
• Using adequate contraceptive measures, be surgically sterile or post-menopausal
• Patients entering this study must be willing to provide tissue from a previous tumor biopsy (if available) for correlative testing. If tissue is not available, a patient will still be eligible for enrollment into the study..

Exclusion Criteria:

• Patients currently receiving cancer therapy
• Use of investigation anti-cancer drug or major surgery, radiotherapy or immunotherapy with the last 21 days
• cardiac disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: AZD2461; oral capsules, continuous dosing and intermittent dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the maximum tolerated dose of AZD 2461 by collection of adverse events, hematology, clinical chemistry data and vital signs.	Day 1
To determine the maximum tolerated dose of AZD 2461 by collection of adverse events, hematology, clinical chemistry data and vital signs.	Day 8
To determine the maximum tolerated dose of AZD 2461 by collection of adverse events, hematology, clinical chemistry data and vital signs.	every 3 weeks after day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
To characterize the pharmacokinetic profile of AZD2461 by collection of blood samples for the measurement of AZD2461 in plasma concentration	Continuous dosing Cycle 1 and 2, Day 1 (pre-dose, 1-hr, 6-hr and 24-hr)
To characterize the pharmacokinetic profile of AZD2461 by collection of blood samples for the measurement of AZD2461 in plasma concentration	Intermittent dosing Cycle 1, Day 1 and Day 14 (pre-dose, 1-hr, 6 hr and 24-hr) Day 18 (+/- 2 days) Cycle 2, Day 1 (pre-dose)
evaluate the pharmacodynamic response after treatment with AZD2461 as the change in PARP (Poly (ADP-ribose) polymerase) inhibition in PBMCs (peripheral blood mononuclear cell)	weekly
To explore the clinical tumor response after treatment with AZD2461 as the assessment of patients with overall tumor response Complete Response (CR), Partial Response (PR), duration of response, stable disease (SD) and time to disease progression	every 6 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Andrew Hughes, MA, MB, ChB, PhD, P, AstraZeneca; Principal Investigator: Dr. Jeffrey Infante, MD, Sarah Cannon Research Institute (SCRI)

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 8, 2010
• First Submitted That Met QC Criteria: November 23, 2010
• First Posted (Estimate): November 24, 2010

Study Record Updates

• Last Update Posted (Estimate): June 6, 2012
• Last Update Submitted That Met QC Criteria: June 5, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Cancer; Solid tumors; Refractory
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: D3660C00001