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

NCT00600496 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: D1532C00004
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 4

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

Conditions

Breast Cancer; Breast Neoplasms; Colon Cancer; Colonic Cancer; Colon Neoplasms; Lung Cancer; Melanoma; Kidney Cancer

Keywords

ARRY-142886; AZD6244; Cancer; Colon Cancer; Breast Cancer; Lung Cancer; Melanoma; Kidney Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• PK of AZD6244 and selected chemotherapies.

  Cycle 1 Day 3 and Cycle 2 day 1

• Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies.

  28 days +

• Tumor response.

  28 days +

Study Arms (4)

1

EXPERIMENTAL

AZD6244 + docetaxel

Drug: AZD6244; Drug: Docetaxel

2

EXPERIMENTAL

AZD6244 + Dacarbazine

Drug: AZD6244; Drug: Dacarbazine

3

EXPERIMENTAL

AZD6244 + Erlotinib

Drug: AZD6244; Drug: Erlotinib

4

EXPERIMENTAL

AZD6244 + Temsirolimus

Drug: AZD6244; Drug: Temsirolimus

Interventions

AZD6244 DRUG

twice daily oral dose

Also known as: ARRY-142886

1; 2; 3; 4

Dacarbazine DRUG

intravenous infusion

2

Erlotinib DRUG

daily oral dose

3

Docetaxel DRUG

intravenous infusion

Also known as: Taxotere®

1

Temsirolimus DRUG

intravenous infusion

4

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

Philadelphia, Pennsylvania, 19111, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Infante JR, Cohen RB, Kim KB, Burris HA 3rd, Curt G, Emeribe U, Clemett D, Tomkinson HK, LoRusso PM. A phase I dose-escalation study of Selumetinib in combination with Erlotinib or Temsirolimus in patients with advanced solid tumors. Invest New Drugs. 2017 Oct;35(5):576-588. doi: 10.1007/s10637-017-0459-7. Epub 2017 Apr 19.

  PMID: 28424891 DERIVED

• LoRusso PM, Infante JR, Kim KB, Burris HA 3rd, Curt G, Emeribe U, Clemett D, Tomkinson HK, Cohen RB. A phase I dose-escalation study of selumetinib in combination with docetaxel or dacarbazine in patients with advanced solid tumors. BMC Cancer. 2017 Mar 6;17(1):173. doi: 10.1186/s12885-017-3143-6.

  PMID: 28264648 DERIVED

• Patel SP, Lazar AJ, Papadopoulos NE, Liu P, Infante JR, Glass MR, Vaughn CS, LoRusso PM, Cohen RB, Davies MA, Kim KB. Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma. Cancer. 2013 Feb 15;119(4):799-805. doi: 10.1002/cncr.27790. Epub 2012 Sep 12.

  PMID: 22972589 DERIVED

Related Links

• D1532C00004 Clinical Report Synopsis

MeSH Terms

Conditions

Breast Neoplasms; Colonic Neoplasms; Lung Neoplasms; Melanoma; Kidney Neoplasms; Neoplasms

Interventions

AZD 6244; Dacarbazine; Erlotinib Hydrochloride; Docetaxel; temsirolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2008
• First Posted: January 25, 2008
• Study Start: December 14, 2007
• Primary Completion: August 20, 2010
• Study Completion: December 31, 2025
• Last Updated: November 13, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• 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 https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• 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 https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (4)