A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886)

Breast Cancer Clinical Trial

Official title:

A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886) When Given in Combination With Standard Doses of Selected Chemotherapies to Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00600496
• Other study ID #: D1532C00004
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 14, 2007
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being conducted to determine if a combination of AZD6244 given orally twice a day with standard doses of selected chemotherapies will be safe and tolerable for cancer patients with advanced solid tumors. The highest tolerated dose of AZD6244 in combination with selected chemotherapies will be evaluated. The study will also investigate how AZD6244 in combination with standard chemotherapies are absorbed, distributed and excreted by the body as well as the length of time that the drugs remain in the body. Initial and periodic assessments will establish patient response to the combination therapies

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 140
• Est. completion date: December 31, 2024
• Est. primary completion date: August 20, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Patients will have measurable and/or non-measurable disease, lacking curative options for whom the selected chemotherapy agents represent the standard of care

• WHO performance status 0-1

• Patients must be able to swallow AZD6244 capsules

Exclusion Criteria:

• Prior treatment with a MEK inhibitor

• Participation in a clinical study during the last 30 days or have not recovered from side effects of an investigational study drug

• Brain metastases or spinal cord compression unless treated and stable (for at least 1 month) off steroids

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma, Renal Cell
• Colon Cancer
• Colon Neoplasms
• Colonic Cancer
• Colonic Neoplasms
• Kidney Cancer
• Kidney Neoplasms
• Lung Cancer
• Melanoma
• Neoplasms

Intervention

Drug:
• AZD6244
twice daily oral dose
• Dacarbazine
intravenous infusion
• Erlotinib
daily oral dose
• Docetaxel
intravenous infusion
• Temsirolimus
intravenous infusion

Locations

Country	Name	City	State
United States	Research Site	Detroit	Michigan
United States	Research Site	Houston	Texas
United States	Research Site	Nashville	Tennessee
United States	Research Site	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies.	Incidence and intensity of adverse events as graded by CTCAE (version 3.0), physical examinations, vital signs (including weight, blood pressure and pulse rate), ECG parameters, MUGA scan and echocardiography, clinical chemistry (including liver function tests), Brain Natriuretic Peptide (BNP), Troponin I, hematology, urinalysis, and ophthalmologic examinations.	28 days +
Secondary	PK of AZD6244 and selected chemotherapies.	The PK parameters will be derived using noncompartmental analysis. The maximum plasma concentrations (Cmax) and the time to reach the maximum plasma concentrations (tmax) will be determined by visual inspection of the plasma concentration-time profiles. The area under the plasma concentration-time curve from zero to 12 hours post dose, AUC(0-12), will be calculated by the linear trapezoidal rule. Where more than one maxima occurs, the reported value will be assigned to the first occurrence.	Cycle 1 Day 3 and Cycle 2 day 1
Secondary	Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies.	The starting dose of AZD6244 in each arm will be 50mg. Continuous dosing (commencing Cycle 1/Day 3 for docetaxel and dacarbazine and Cycle 1/Day 8 for erlotinib and temsirolimus) will be BD. The AZD6244 dose may be maintained or reduced.	28 days +
Secondary	Tumor response.	To make a preliminary assessment of tumor response as measured by Objective Response Rate (ORR) per investigator's assessment using Response Evaluation Criteria in Solid Tumors (RECIST) when AZD6244 Hyd-Sulfate is given in combination with standard doses of selected chemotherapies.	28 days +

External Links

•   D1532C00004 Clinical Report Synopsis