Stage IV Pancreatic Cancer MedDRA version: 14.1 Level: PT Classification code 10059326 Term: Pancreatic carcinoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MK-0752
Product Code: MK-0752
Pharmaceutical Form: Capsule, hard
Current Sponsor code: MK-0752
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
P
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically proven Stage IV pancreatic ductal adenocarcinoma. 2. Previous chemotherapy for advanced disease is not permitted. Adjuvant chemotherapy is allowed provided it is completed more than 6 months prior to treatment. If adjuvant gemcitabine treatment was given, the patient must have tolerated a dose of at least 800mg/m2. 3. Assessable disease. Tumour assessment and measurements (RECIST, where appropriate) must be done within four weeks before the patient receives the first dose of MK-0752 (Day -14). Clinical measurements must be done within one week before the patient receiving the first dose of MK-0752. 4. Tissue that is assessed by the Investigator as being accessible to biopsy- for patients recruited in the dose escalation phase I only. If three patients have successfully undergone baseline and Day -7 biopsies at a particular dose level, biopsies are not required for further patients recruited at the same dose and this criterion is not applicable). 5. Life expectancy of at least 12 weeks. 6. World Health Organisation (WHO) performance status of 0 or 1. 7. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient goes on study (Day -14). Laboratory Test Value required Haemoglobin (Hb) = 9.0 g/dl Absolute neutrophil count = 1.5 x 10(9)/L Platelet count = 100 x 10(9)/L Serum bilirubin = 1.5 x upper limit of normal (ULN) Alanine amino-transferase (ALT) = 2.5 x ULN unless raised due to liver metastases in which case up to 5 x ULN is permissible Prothrombin time (PT) = 1.5 x ULN Calculated creatinine clearance = 50 mL/min 8. 18 years or over. 9. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 47 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: 1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, or use of other investigational medicinal products. 2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient. 3. Known brain metastases (those patients with stable symptoms within the four weeks prior to receiving MK-0752, are on a stable steroid dose and are able to give informed consent will be considered eligible). 4. Patients taking warfarin (unless it is possible for the patient to be switched to a low molecular weight heparin for the duration of the study). 5. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible. 6. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate. 7. Major thoracic or abdominal surgery from which the patient has not yet recovered. 8. At high medical risk because of non-malignant systemic disease including active uncontrolled infection. 9. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 10. Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years or more and are deemed at negligible risk for recurrence, are eligible for the study. 11. Concurrent congestive heart failure, prior history of class III/IV cardiac disease (New York Heart Association [NYHA]), prior history of cardiac ischaemia or prior history of cardiac arrhythmia. 12. Is a participant or plans to participate in another interventional clinical study, whilst taking part in this Phase I/IIa study of MK-0752. Participation in an observational study would be acceptable. 13. Any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The trial is conducted in two phases and the objectives are: Phase I (a) To recommend a dose for further Phase II evaluation of MK- 0752 in combination with gemcitabine (b) To determine the safety and tolerability of MK-0752 in combination with gemcitabine in patients with Stage IV pancreatic cancer Phase II a) To measure survival at six months ;Secondary Objective: (a) To evaluate tumour response following MK-0752 administered orally on Days 1, 8, 15 and 22, in combination with gemcitabine administered intravenously on Days 1, 8 and 15 of a 28 day cycle (b) To measure the time to disease progression and one year survival (c) To measure percentage change in CA19-9 levels (d) To investigate the pharmacokinetic profile of MK-0752 in plasma, when administered with and without gemcitabine;Primary end point(s): Phase I (a) Either; the maximum tolerated dose (MTD) of MK 0752 in combination with gemcitabine or the single agent MK-0752 RP2D in combination with either 800 mg/m2 or 1000 mg/m2 gemcitabine as agreed by DDO and the clinicians. b) Determining causality of each adverse event to the combination of MK-0752 and gemcitabine, and grading severity according to NCI CTCAE Version 4.02 Phase II a) The proportion of patients alive at six months post Cycle 1, Day 1 of MK-0752 ;Timepoint(s) of evaluation of this end point: Phase 1 (b) AEs assessed from time of consent up to 28 days after the last administration of MK-0752 or gemcitabine Phase II (a) Six months post day 1 of MK-0752 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): (a) Any response (complete response (CR) or partial response (PR), or stable disease (SD) in any of the patients as defined by RECIST criteria using conventional computerised tomography (CT) measurements (b) i) Progression free survival ii) survival at one year (c) Percentage change in CA19-9 levels in patients with elevated CA19-9 levels at baseline ;Timepoint(s) of evaluation of this end point: (a) Baseline, after every 2 cycles, at off study visit (b) i) Every two months following study up to 1 year, then at routine clinic visits until 1 year after the last patient is treated on the study. (b) ii) One year post cycle on day 1. (c) Day -14 of cycle 1. Day 1 of every cycle. | — |
Countries
United Kingdom
Contacts
Public ContactDrug Development Office
Cancer Research UK
Outcome results
None listed