MK0752 And Gemcitabine Hydrochloride In Treating Patients With Stage III And IV Pancreatic Cancer That Cannot Be Removed By Surgery

Study Overview

MK0752 and Gemcitabine Hydrochloride in Treating Patients With Stage III and IV Pancreatic Cancer That Cannot Be Removed by Surgery

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.

OBJECTIVES: Primary * 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) Secondary * 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. Tertiary * 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

Pancreatic Cancer

DRUG: Notch signaling pathway inhibitor MK0752
DRUG: gemcitabine hydrochloride
OTHER: imaging biomarker analysis
OTHER: laboratory biomarker analysis
OTHER: pharmacological study

CDR0000669535
CRUK-CR0720-11
CRUK-MK-0752
EUDRACT-2008-004829-42

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-04-01	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2015-10-13
First Submitted that Met QC Criteria 2010-04-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2015-10-14
First Posted (ESTIMATED) 2010-04-02	Results First Posted N/A	Last Verified 2015-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
N/A

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
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

Secondary Outcome Measures	Measure Description	Time Frame
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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed ductal adenocarcinoma of the pancreas

Stage III and IV, unresectable disease
Assessable disease by endoscopic ultrasound or CT guidance
Tissue that is assessed by the Investigator as being accessible to biopsy - for patients recruited to dose escalation phase where three previous patients have not already provided biopsies
No known brain metastases

Patients with stable symptoms within the past 4 weeks, on a stable dose of steroids, and able to give informed consent are eligible

WHO performance status 0-1
Life expectancy ≥ 12 weeks
Hemoglobin ≥ 9.0 g/dL
Absolute neutrophil count ≥ 1.5 x 10^9/L
Platelet count ≥ 100 x 10^9/L
Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT ≤ 2.5 times ULN (≤ 5 times ULN if due to liver metastases)
PT ≤ 1.5 times ULN
Creatinine clearance ≥ 50 mL/min (uncorrected)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use two forms of highly effective contraception (females) 4 weeks prior to, during, and for 6 months after completion of study therapy or 1 form of highly effective contraception (males) during and for 6 months after completion of study therapy
Written (signed and dated) informed consent and capable of cooperating with treatment and follow-up
No nonmalignant systemic disease, including active uncontrolled infection, that confers a high medical risk to the patient
No known serologically positive HIV or hepatitis B or C infection
No other concurrent malignancies except adequately treated cone-biopsied carcinoma in situ of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease ≥ 5 years, and are deemed at negligible risk for recurrence
No concurrent congestive heart failure
No prior history of cardiac disease (New York Heart Association class III-IV disease), cardiac ischemia, or cardiac arrhythmia
No other condition that, in the investigator's opinion, would not make the patient a good recommendation for the clinical trial

See Disease Characteristics
Recovered from prior treatments
Previous chemotherapy for advanced disease is permitted. If gemcitabine treatment was given previously, the patient must have tolerated a dose of at least 800mg/m2. Previous chemotherapy for malignant disease must be complete at least 3 weeks before treatment on this trial (six weeks for mitomycin C)
No major thoracic or abdominal surgery from which the patient has not yet recovered
No concurrent participation or planned participation in another interventional clinical study

Concurrent participation in an observational study allowed
No concurrent warfarin

Low molecular weight heparin allowed
No concurrent radiotherapy (except palliative for bone pain), endocrine therapy, or immunotherapy
No other concurrent anticancer therapy or investigational drugs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Duncan Jodrell, MD, Cambridge University Hospitals NHS Foundation Trust

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record