Study of Selumetinib (AZD6244)(ARRY-142886) in Combination With Irinotecan in Previously Treated Patients With Colorec

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: AZD6244; Drug: Irinotecan

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

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States
      • Research Site
    • Palm Springs, California, United States
      • Research Site
  • Colorado
    • Aurora, Colorado, United States
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States
      • Research Site
  • Delaware
    • Newark, Delaware, United States
      • Research Site
  • Florida
    • Miami Beach, Florida, United States
      • Research Site
  • New York
    • New York, New York, United States
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States
      • Reserach Site
    • Greenville, North Carolina, United States
      • Research Site
    • Washington, North Carolina, United States
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • Washington
    • Seattle, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Selumetinib (AZD6244) in combination with irinotecan	Drug: AZD6244; 50 or 75mg, capsules, PO, BID, 28 days; Other Names: Selumetinib; Drug: Irinotecan; 180mg/m2, IV, Day 1& 15 of each cycle; Other Names: Camptosar; Campto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Finding will be calculated based upon toxicity screening and dose modification guidelines within protocol.	AEs will be assessed at each cycle visit, discontinuation treatment visit, and 30 days post last day of study treatment
Objective Response Rate will be assessed by the RECIST guideline documented in the European Journal of Cancer, 2009.	Tumor evaluation via RECIST guidelines will be done on screening visit, day 22 of every other cycle, and treatment discontinuation visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety of combination of Selumetinib (AZD6244) with irinotecan by SAE and AE documentation	AEs will be assesed at the screening visit, each cycle visit, treatment discontinuation date, and 30 days post last day of study treatment
PK of Selumetinib (AZD6244), N-desmethyl Selumetinib(AZD6244) and selumetinib (AZD6244) amide in combination with irinotecan	PK sample draws will take place on Day 1 and 15 of first cycle
Progression Free Survival (PFS) for patients with K-ras or B-raf mutations treated with combination of irinotecan and Selumetinib (AZD6244)	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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Howard Hochster, MD, Yale University; Principal Investigator: Lawrence Leichman, MD, Desert Regional Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: April 30, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): January 14, 2013
• Last Update Submitted That Met QC Criteria: January 11, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: colorectal; second line therapy; K-ras or B-raf mutations; response rate; Progression Free Survival
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: D9010C00009; AGICC 09CRC02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No