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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00600496
Recruitment Status : Active, not recruiting
First Posted : January 25, 2008
Last Update Posted : September 22, 2021
Information provided by (Responsible Party):

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

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Study Type : Interventional  (Clinical Trial)
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 : December 14, 2007
Actual Primary Completion Date : August 20, 2010
Estimated Study Completion Date : December 31, 2021

Arm Intervention/treatment
Experimental: 1
AZD6244 + docetaxel
Drug: AZD6244
twice daily oral dose
Other Name: ARRY-142886

Drug: Docetaxel
intravenous infusion
Other Name: Taxotere®

Experimental: 2
AZD6244 + Dacarbazine
Drug: AZD6244
twice daily oral dose
Other Name: ARRY-142886

Drug: Dacarbazine
intravenous infusion

Experimental: 3
AZD6244 + Erlotinib
Drug: AZD6244
twice daily oral dose
Other Name: ARRY-142886

Drug: Erlotinib
daily oral dose

Experimental: 4
AZD6244 + Temsirolimus
Drug: AZD6244
twice daily oral dose
Other Name: ARRY-142886

Drug: Temsirolimus
intravenous infusion

Primary Outcome Measures :
  1. Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies. [ Time Frame: 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 :
  1. PK of AZD6244 and selected chemotherapies. [ Time Frame: 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.

  2. Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies. [ Time Frame: 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.

  3. Tumor response. [ Time Frame: 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00600496

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United States, Michigan
Research Site
Detroit, Michigan, United States, 48201
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37203
United States, Texas
Research Site
Houston, Texas, United States, 77030
Sponsors and Collaborators
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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
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: AstraZeneca Identifier: NCT00600496    
Other Study ID Numbers: D1532C00004
First Posted: January 25, 2008    Key Record Dates
Last Update Posted: September 22, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at
Keywords provided by AstraZeneca:
Colon Cancer
Breast Cancer
Lung Cancer
Kidney Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Colonic Neoplasms
Kidney Neoplasms
Carcinoma, Renal Cell
Neoplasms by Site
Breast Diseases
Skin Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial