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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: AZD6244
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal, second line therapy, K-ras or B-raf mutations, response rate, Progression Free Survival