Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations
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|ClinicalTrials.gov Identifier: NCT03040986|
Recruitment Status : Active, not recruiting
First Posted : February 2, 2017
Last Update Posted : November 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|KRAS NP_004976.2:p.G12R Stage III Pancreatic Cancer AJCC v6 and v7 Stage IV Pancreatic Cancer AJCC v6 and v7||Other: Laboratory Biomarker Analysis Drug: Selumetinib Sulfate||Phase 2|
I. Determine the objective response rate to selumetinib sulfate (selumetinib) administered as 75 mg orally twice daily on a continuous schedule in patients with advanced pancreas cancer harboring KRAS G12R mutations.
I. To determine the progression free survival of patients with locally advanced, unresectable and stage IV pancreas cancer treated with selumetinib monotherapy.
II. To evaluate the safety of selumetinib in patients with advanced pancreas cancer.
III. To determine the impact of additional genetic alterations on the response to selumetinib in pancreas cancer harboring KRAS G12R mutations.
IV. To develop a clinically applicable biomarker predicting response to selumetinib in pancreas cancer harboring KRAS G12R mutations.
Patients receive selumetinib sulfate orally (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for 52 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Selumetinib (AZD6244) for the Treatment of Advanced Pancreas Cancer Harboring KRAS G12R Mutations|
|Actual Study Start Date :||July 21, 2017|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Treatment (selumetinib sulfate)
Patients receive selumetinib sulfate PO BID. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity
Other: Laboratory Biomarker Analysis
Drug: Selumetinib Sulfate
- Production of adequate numbers of clinical responses with selumetinib sulfate monotherapy [ Time Frame: Up to 52 weeks ]Will determine whether this novel agent is able to be associated with a response rate (partial response [PR] + complete response) that can rule out 5% (p0=0.05) in favor of an improved response rate of 30% (p1=0.30).
- Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 52 weeks ]Will be calculated using the Kaplan-Meier method.
- Incidence of adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 52 weeks ]If there are 5 or more patients who experience grade 3 or greater toxicity attributable to the agent, then comparisons between this cohort and patients who tolerated the same course of selumetinib without toxicity across grades of toxicity with respect to outcome (response) and clinicopathological parameters (age, sex, type of metastatic involvement vs locally advanced) may be done using a Kruskal-Wallis test. Otherwise, toxicities will be tabulated and described.
- Response to selumetinib sulfate (PR as defined by Response Evaluation Criteria in Solid Tumors) [ Time Frame: Up to 52 weeks ]Will be associated with the presence of concomitant activating oncogene mutations or loss of tumor suppressor function will be presented descriptively to estimate the response rates according to those characteristics.
- Semi-quantitative measurements of CNKSR1 [ Time Frame: Up to 52 weeks ]Comparisons will be descriptively to estimate the differences of the expression level in pancreas cancer tissues and clinical outcome variables.
- Change in circulating tumor deoxyribonucleic acid (ctDNA) and alteration in in somatic variants [ Time Frame: Baseline up to 52 weeks ]Compared between baseline and repeat profiling (integrated biomarker; voluntary) will be evaluated for change from baseline levels and the estimated changes will be reported.
- Predictive biomarkers for response to selumetinib [ Time Frame: Up to 52 weeks ]Presence of variants identified in the 50-cancer gene panel will be compared with response, presenting the results in a 2x2 table with findings reported descriptively. Pre-treatment ctDNA levels will be divided into groups to separate aberrant values from the rest. The cutoffs will be > and < 2 standard deviations of the mean, with the cutoffs applied to both ctDNA levels. Based on these groups, resulting in patients with cell free deoxyribonucleic acid (cfDNA) transcripts levels > 2 standard deviation (SD) above the mean, patients with cfDNA transcripts levels < 2 SD below the mean, and the rest in between, the categorical results will be evaluated and reported relative to response vs. non-response in a descriptive manner.
- Longitudinal biomarker measuring response to treatment [ Time Frame: Up to 52 weeks ]cfDNA transcript levels will be followed from the start of treatment every (q)2 weeks and the change to pre-treatment will be plotted for each timepoint in a spider plot format. This will be a descriptive presentation only. Variant profile derived from voluntary repeat biopsies will be compared to pre-treatment variant profile and gain of variants (adjusted for similar sequencing depth) will be recorded. This will be a descriptive presentation only.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03040986
|United States, California|
|Los Angeles County-USC Medical Center|
|Los Angeles, California, United States, 90033|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Kentucky|
|University of Kentucky/Markey Cancer Center|
|Lexington, Kentucky, United States, 40536|
|United States, Maryland|
|NCI - Center for Cancer Research|
|Bethesda, Maryland, United States, 20892|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Udo Rudloff||National Cancer Institute LAO|