MK0752 and Gemcitabine Hydrochloride in Treating Patients With Stage III and IV Pancreatic Cancer That Cannot Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT01098344|
Recruitment Status : Completed
First Posted : April 2, 2010
Last Update Posted : October 14, 2015
RATIONALE: MK0752 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving MK0752 together with gemcitabine hydrochloride may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of giving MK0752 together with gemcitabine hydrochloride and to see how well it works in treating patients with stage III or IV pancreatic cancer that cannot be removed by surgery.
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Cancer||Drug: Notch signaling pathway inhibitor MK0752 Drug: gemcitabine hydrochloride Other: imaging biomarker analysis Other: laboratory biomarker analysis Other: pharmacological study||Phase 1|
- To determine the recommended phase II dose of MK0752 in combination with gemcitabine hydrochloride in patients with unresectable stage III and IV pancreatic cancer. (Phase I)
- To evaluate tumor response in patients treated with this regimen.
- To determine the time to disease progression and 6 months and 1-year survival.
- To determine the percentage of change in CA19-9 levels.
- To assess target inhibition of MK0752 in plasma.
- To explore the feasibility of measuring MK0752 levels in tumor tissue.
- To establish relationships between measures of tumor expression of molecular target and objective tumor response.
- To determine the pharmacokinetic profile of MK0752 in plasma when administered with and without gemcitabine hydrochloride.
OUTLINE: This is a multicenter, phase I, dose-escalation study of MK0752 and gemcitabine hydrochloride.
Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15. Patients receive oral MK0752 on days -14, -7, 1, 8, 15, and 22 in course 1 only and on days 1, 8, 15, and 22 beginning in course 2 and for all subsequent courses. Treatment with MK0752 and gemcitabine hydrochloride repeats every 28 days* for 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *The first course is 42 days.
Patients undergo biopsy of tumor at baseline and on day -7. Tumor samples are analyzed to determine Notch pathway inhibition via IHC and qualitative RT-PCR analysis and for MK0752 concentrations. Hair follicle (from the head) samples are collected at baseline and on day -7 to determine Notch pathway inhibition via RT-PCR. Blood samples are collected periodically to determine changes in CA 19-9 levels and MK0752 concentrations.
After completion of study treatment, patients are followed for 28 days and then every 2 months for 1 year. Patients will then be followed up as part of their normal clinic visits for up to one year after the last patient was treated on the study.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Masking:||None (Open Label)|
|Official Title:||A Cancer Research UK Phase I Trial of an Oral Notch Inhibitor (MK-0752) in Combination With Gemcitabine in Patients With Stage III and IV Pancreatic Cancer|
|Study Start Date :||April 2010|
|Actual Primary Completion Date :||October 2014|
|Actual Study Completion Date :||October 2014|
- Maximum-tolerated dose of MK0752 in combination with gemcitabine hydrochloride OR the single agent recommended Phase II dose in combination with either 800 mg/m² or 1000 mg/m² as agreed by DDO and clinicians
- Adverse event and severity according to NCI CTCAE Version 4.02
- Complete response, partial response, or stable disease as defined by RECIST criteria
- Progression-free survival
- Survival at 1 year
- Percentage change in CA19-9 levels
- Plasma concentrations of MK0752
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): NCT01098344
|Cambridge, England, United Kingdom, CB2 2QQ|
|Leicester Royal Infirmary|
|Leicester, England, United Kingdom, LE1 5WW|
|Barts and the London School of Medicine|
|London, England, United Kingdom, EC1M 6BQ|
|Beatson West of Scotland Cancer Centre|
|Glasgow, Scotland, United Kingdom, G12 0YN|
|St James' Hospital|
|Leeds, United Kingdom, L59 7TF|
|Principal Investigator:||Duncan Jodrell, MD||Cambridge University Hospitals NHS Foundation Trust|