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

AstraZeneca140 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

140

Conditions

Breast Cancer Breast Neoplasms Colon Cancer Colonic Cancer Colon Neoplasms

Interventions

AZD6244DRUG

twice daily oral dose

DacarbazineDRUG

intravenous infusion

ErlotinibDRUG

daily oral dose

DocetaxelDRUG

intravenous infusion

TemsirolimusDRUG

intravenous infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

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

Locations (4)

Research Site

Detroit, Michigan, United States

Research Site

Philadelphia, Pennsylvania, United States

Research Site

Nashville, Tennessee, United States

Research Site

Houston, Texas, United States

Outcomes

Primary Outcomes

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.

Time frame: 28 days +

Secondary Outcomes

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.

Time frame: Cycle 1 Day 3 and Cycle 2 day 1

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.

Time frame: 28 days +

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.

Time frame: 28 days +