An Open-Label, Dose-Escalation Study of AZD2461

Refractory Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01247168
• Other study ID #: D3660C00001
• Status: Completed
• Phase: Phase 1
• First received: November 8, 2010
• Last updated: June 5, 2012
• Start date: November 2010
• Est. completion date: May 2011

Study information

• Verified date: June 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer Tumor
• Neoplasms
• Refractory Solid Tumors

Intervention

Drug:
• AZD2461
oral capsules, continuous dosing and intermittent dosing

Locations

Country	Name	City	State
United States	Research Site	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum tolerated dose of AZD 2461 by collection of adverse events, hematology, clinical chemistry data and vital signs.		Day 1	Yes
Primary	To determine the maximum tolerated dose of AZD 2461 by collection of adverse events, hematology, clinical chemistry data and vital signs.		Day 8	Yes
Primary	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	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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	No
Secondary	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	Yes