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

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT00600496

Collaborator

(none)

140

Enrollment

Locations

Arms

180.5

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Breast Neoplasms Colon Cancer Colonic Cancer Colon Neoplasms Lung Cancer Melanoma Kidney Cancer	Drug: AZD6244 Drug: Dacarbazine Drug: Erlotinib Drug: Docetaxel Drug: Temsirolimus	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

140 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 14, 2007

Actual Primary Completion Date :

Aug 20, 2010

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 AZD6244 + docetaxel	Drug: AZD6244 twice daily oral dose Other Names: ARRY-142886 Drug: Docetaxel intravenous infusion Other Names: Taxotere®
Experimental: 2 AZD6244 + Dacarbazine	Drug: AZD6244 twice daily oral dose Other Names: ARRY-142886 Drug: Dacarbazine intravenous infusion
Experimental: 3 AZD6244 + Erlotinib	Drug: AZD6244 twice daily oral dose Other Names: ARRY-142886 Drug: Erlotinib daily oral dose
Experimental: 4 AZD6244 + Temsirolimus	Drug: AZD6244 twice daily oral dose Other Names: ARRY-142886 Drug: Temsirolimus intravenous infusion

Outcome Measures

Primary Outcome Measures

Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies. [28 days +]
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.

Secondary Outcome Measures

PK of AZD6244 and selected chemotherapies. [Cycle 1 Day 3 and Cycle 2 day 1]
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.
Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies. [28 days +]
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.
Tumor response. [28 days +]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Detroit	Michigan	United States	48201
2	Research Site	Philadelphia	Pennsylvania	United States	19111
3	Research Site	Nashville	Tennessee	United States	37203
4	Research Site	Houston	Texas	United States	77030

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: Patricia LoRusso, DO, Barbara Ann Karmanos Cancer Institute
Principal Investigator: Roger Cohen, MD, Fox Chase Cancer Center
Principal Investigator: Jeffrey Infante, MD, SCRI Development Innovations, LLC
Principal Investigator: Kevin Kim, MD, M.D. Anderson Cancer Center