Clinical trial NCT01116271: Study of Selumetinib (AZD6244)(ARRY-142886) in Combination With Irinotecan in Previously Treated Patients With Colorec
Official title: A Dose Finding and Phase II Study of Selumetinib (AZD6244) (Hyd-Sulfate) in Combination With Irinotecan, in 2nd Line Patients With K-ras or B-raf Mutation Positive Advanced or Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: colorectal
second line therapy
K-ras or B-raf mutations
response rate
Progression Free Survival
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-05-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether treatment with Selumetinib (AZD6244) (Hyd-Sulfate) in combination with Irinotecan as a second treatment in patients with K-ras or B-raf mutation will prevent tumor progression and prolong progression free survival.

Detailed description: A Dose Finding and Phase II Study of Selumetinib (AZD6244) (Hyd-Sulfate) in Combination with Irinotecan, in 2nd Line Patients with K-ras or B-raf Mutation Positive Advanced or Metastatic Colorectal Cancer

Eligibility criteria: Inclusion Criteria:

- Histological or cytological confirmation of advanced or metastatic colorectal cancer with available tissue and tumor sample confirmed as K-ras or B-raf mutation positive. Current failure of 1st line anti-cancer therapy with an oxaliplatin and bevacizumab based regimen or patients relapsing within 12 months of completing adjuvant FOLFOX .

Exclusion Criteria:

- Treatment within 14 days prior to first study treatment with conventional therapy or treatment within 28 days prior to first study treatment with an investigational drug Prior treatment with a MEK or B-raf inhibitor or any irinotecan-containing regimen Prior treatment with a MEK or B-raf inhibitor or any irinotecan-containing regimen

Primary outcomes:
measure: Dose Finding will be calculated based upon toxicity screening and dose modification guidelines within protocol.
timeFrame: AEs will be assessed at each cycle visit, discontinuation treatment visit, and 30 days post last day of study treatment
measure: Objective Response Rate will be assessed by the RECIST guideline documented in the European Journal of Cancer, 2009.
timeFrame: Tumor evaluation via RECIST guidelines will be done on screening visit, day 22 of every other cycle, and treatment discontinuation visit
Secondary outcomes:
measure: Safety of combination of Selumetinib (AZD6244) with irinotecan by SAE and AE documentation
timeFrame: AEs will be assesed at the screening visit, each cycle visit, treatment discontinuation date, and 30 days post last day of study treatment
measure: PK of Selumetinib (AZD6244), N-desmethyl Selumetinib(AZD6244) and selumetinib (AZD6244) amide in combination with irinotecan
timeFrame: PK sample draws will take place on Day 1 and 15 of first cycle
measure: Progression Free Survival (PFS) for patients with K-ras or B-raf mutations treated with combination of irinotecan and Selumetinib (AZD6244)
timeFrame: PFS will be determined via the RECIST guidelines on tumor measurement done on day 22 of every other cycle and on the treatment discontinuation visit
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Palm Springs
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Miami Beach
country: United States
facility: Research Site
state: Florida
city: New York
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Reserach Site
state: North Carolina
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Washington
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Seattle
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: Yale University
name: Howard Hochster, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Desert Regional Comprehensive Cancer Center
name: Lawrence Leichman, MD
role: PRINCIPAL_INVESTIGATOR
References: