Clinical trial NCT00600496: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-01-25
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies.
timeFrame: 28 days +
Secondary outcomes:
measure: PK of AZD6244 and selected chemotherapies.
timeFrame: Cycle 1 Day 3 and Cycle 2 day 1
measure: Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies.
timeFrame: 28 days +
measure: Tumor response.
timeFrame: 28 days +
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Patricia LoRusso, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Fox Chase Cancer Center
name: Roger Cohen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SCRI Development Innovations, LLC
name: Jeffrey Infante, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Kevin Kim, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.