Colorectal Cancer
Conditions
Keywords
colorectal, second line therapy, K-ras or B-raf mutations, response rate, Progression Free Survival
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
Interventions
DRUGAZD6244
50 or 75mg, capsules, PO, BID, 28 days
DRUGIrinotecan
180mg/m2, IV, Day 1& 15 of each cycle
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| 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 |
Countries
United States
Outcome results
None listed