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 Drug: selumetinib Other: laboratory biomarker analysis||Phase 2|
|Study Design:||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 ]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.
- Survival at 24 Weeks [ Time Frame: 24 weeks ]Percent survival at 24 weeks (6 months)
- 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 ]
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.
Response and progression are evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(Macdonald et al.):205-216, 2000]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used. Progressive Disease is defined as a 20% or higher increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
- 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 ]The proportion of patients with CA19-9 response.
- Objective Radiographic Response by RECIST Criteria [ Time Frame: Up to 2 years ]
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.
Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR, >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.
- 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 ]Tabulation of type of adverse events (AE) and the incidence of grade 3 and 4 for each AE
- Number of Patients With Dose Modifications and Reason for Dose Modification. [ Time Frame: Up to final day of study treatment ]Tabulation of the reasons for dose modification with number of patients
- Protein Expression Levels in Pretherapeutic Core Biopsies [ Time Frame: Up to 2 years ]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 ]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 ]
The association between candidate plasma biomarkers of interest, their longitudinal changes, and patient outcomes as measured by OS, PFS, and radiographic and biomarker response.
Specifically, correlation of the relative change in allelic frequency of mutations present in both pre-treatment and on-treatment blood samples versus percent change in CA19-9.
|Study Start Date:||November 2010|
|Study Completion Date:||September 2014|
|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|