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

Primary Purpose

Breast Cancer, Breast Neoplasms, Colon Cancer

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD6244
Dacarbazine
Erlotinib
Docetaxel
Temsirolimus
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring ARRY-142886, AZD6244, Cancer, Colon Cancer, Breast Cancer, Lung Cancer, Melanoma, Kidney Cancer

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

1

2

3

4

Arm Description

AZD6244 + docetaxel

AZD6244 + Dacarbazine

AZD6244 + Erlotinib

AZD6244 + Temsirolimus

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
January 15, 2008
Last Updated
October 16, 2023
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00600496
Brief Title
A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886)
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 14, 2007 (Actual)
Primary Completion Date
August 20, 2010 (Actual)
Study Completion Date
December 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
140 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
AZD6244 + docetaxel
Arm Title
2
Arm Type
Experimental
Arm Description
AZD6244 + Dacarbazine
Arm Title
3
Arm Type
Experimental
Arm Description
AZD6244 + Erlotinib
Arm Title
4
Arm Type
Experimental
Arm Description
AZD6244 + Temsirolimus
Intervention Type
Drug
Intervention Name(s)
AZD6244
Other Intervention Name(s)
ARRY-142886
Intervention Description
twice daily oral dose
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Intervention Description
intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
daily oral dose
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxotere®
Intervention Description
intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Temsirolimus
Intervention Description
intravenous infusion
Primary Outcome Measure Information:
Title
Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies.
Description
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 Outcome Measure Information:
Title
PK of AZD6244 and selected chemotherapies.
Description
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
Title
Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies.
Description
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 +
Title
Tumor response.
Description
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 +

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patricia LoRusso, DO
Organizational Affiliation
Barbara Ann Karmanos Cancer Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Roger Cohen, MD
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jeffrey Infante, MD
Organizational Affiliation
SCRI Development Innovations, LLC
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kevin Kim, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing 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
IPD Sharing 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
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Citations:
PubMed Identifier
28424891
Citation
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. Erratum In: Invest New Drugs. 2017 Jul 5;:
Results Reference
derived
PubMed Identifier
28264648
Citation
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.
Results Reference
derived
PubMed Identifier
22972589
Citation
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.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1170&filename=D1532C00004_Study_Synopsis.pdf
Description
D1532C00004 Clinical Report Synopsis

Learn more about this trial

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

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