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

NCT ID: NCT01098344

Last Updated: 2015-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2014-10-31

Brief Summary

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.

Detailed Description

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

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Notch signaling pathway inhibitor MK0752

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

imaging biomarker analysis

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research UK

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Duncan Jodrell, MD

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospitals NHS Foundation Trust

Locations

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Leicester Royal Infirmary

Leicester, England, United Kingdom

Barts and the London School of Medicine

London, England, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

St James' Hospital

Leeds, , United Kingdom

Countries

United Kingdom

Other Identifiers

CRUK-CR0720-11

Identifier Type: -

Identifier Source: secondary_id

CRUK-MK-0752

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-004829-42

Identifier Type: -

Identifier Source: secondary_id

CDR0000669535

Identifier Type: -

Identifier Source: org_study_id