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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00600496
First received: January 15, 2008
Last updated: March 21, 2013
Last verified: March 2013
History of Changes
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies. [ Time Frame: 28 days + ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Cycle 1 Day 3 and Cycle 2 day 1 ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 days + ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 days + ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 80
Study Start Date: December 2007
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00600496

Locations
United States, Michigan
Research Site
Detroit, Michigan, United States
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States
United States, Tennessee
Research Site
Nashville, Tennessee, United States
United States, Texas
Research Site
Houston, Texas, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Patricia LoRusso, DO Karmanos Cancer Institute
Principal Investigator: Roger Cohen, MD Fox Chase Cancer Center
Principal Investigator: Jeffrey Infante, MD Sarah Cannon Research Institute
Principal Investigator: Kevin Kim, MD M.D. Anderson Cancer Center
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00600496     History of Changes
Other Study ID Numbers: D1532C00004
Study First Received: January 15, 2008
Last Updated: March 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
ARRY-142886
AZD6244
Cancer
Colon Cancer
 Breast Cancer
Lung Cancer
Melanoma
Kidney Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Colonic Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Lung Neoplasms
Melanoma
Neoplasms by Site
Breast Diseases
Skin Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
 Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 16, 2013