Selumetinib and Erlotinib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of AZD6244 Plus Erlotinib for the Second-Line Treatment of Advanced Pancreatic Adenocarcinoma|
- Overall survival (OS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Survival will be calculated according to the method of Kaplan and Meier. Both actual and estimated probability of being alive (along with a 95% confidence interval) at 24 weeks (6 months) and for any multiple of 6 months will be calculated for which the number of uncensored subjects is not smaller than 10.
- Progression-free survival (PFS) [ Time Frame: From first dose of study treatment to the date of objective progression, or death due to cancer or unknown cause, or to the date of withdrawal from the trial from unknown reasons, assessed up to 2 years ] [ Designated as safety issue: No ]Calculated according to the method of Kaplan and Meier. Actual and estimated probability of being alive and progression-free, along with a 95% confidence interval, will be calculated.
- CA19-9 biomarker response (defined as a 50% decline in serum CA19-9 level from baseline in patients with > 2 x ULN CA19-9 measurement) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]The proportion of patients with CA19-9 response will be estimated along with 95% confidence intervals in the subset of patients with elevated CA19-9 at baseline.
- Objective radiographic response by RECIST criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Patient's best overall response will be tabulated by level; proportions of complete response (CR) and of CR+partial response will be calculated along with 95% confidence intervals.
- Incidence of toxicities graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]Toxicities will be tabulated by grade and organ system. Number of patients with dose modifications and reason for dose modification will also be tabulated.
- Protein expression levels in pretherapeutic core biopsies [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Logistic regression models will be used to associate baseline protein markers and best objective response. Cox models will be used to associate baseline protein markers with overall and progression-free survival. Each selected protein markers will be evaluated individually and ranked by the corresponding p-values. Combinations of markers will also be explored.
- Circulating tumor cell (CTC) analysis [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]The association between baseline CTC numbers, their longitudinal changes, and patient outcomes as measured by OS, PFS, and radiographic and biomarker response will be evaluated. The association between expression level of protein markers in CTC with biopsy samples using Pearson's correlation and by unsupervised hierarchical clustering of samples using Pearson correlation as the distance metric will be assessed. Association of longitudinal protein markers in CTC with patient OS will be evaluated using the joint models of longitudinal observations.
- Plasma biomarkers potentially predictive of dual MEK/EGFR inhibition [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]The association between candidate plasma biomarkers of interest, their longitudinal changes, and patient outcomes as measured by OS, PFS, and radiographic and biomarker response.
|Study Start Date:||November 2010|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (erlotinib hydrochloride, selumetinib)
Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: erlotinib hydrochloride
Other Names:Drug: selumetinib
Other Names:Other: laboratory biomarker analysis
l. To assess overall survival (as measured by median survival and proportion of patients alive at 24 weeks) in patients with advanced pancreatic cancer who have received one prior line of systemic therapy when treated with the combination of AZD6244 (selumetinib) and erlotinib (erlotinib hydrochloride).
I. Progression-free survival (median progression-free survival [PFS] and proportion of patients with PFS at 12 and 24 weeks).
II. Cancer antigen (CA)19-9 biomarker response (defined as a 50% decline in serum CA19-9 level from baseline in patients with > 2 x upper limit of normal [ULN] CA19-9 measurement).
III. Objective radiographic response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
IV. Safety and toxicity profile of the combination of AZ6244 and erlotinib.
Patients receive selumetinib orally (PO) once daily (QD) and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2-3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01222689
|United States, California|
|San Francisco, California, United States, 94115|
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Andrew Ko||UCSF-Mount Zion|