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

NCT01098344 | Completed Phase 1

• 4 other identifiers: CDR0000669535CRUK-CR0720-11CRUK-MK-0752EUDRACT-2008-004829-42
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 5

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.

Conditions

Pancreatic Cancer

Keywords

stage III pancreatic cancer; stage IV pancreatic cancer; duct cell adenocarcinoma of the pancreas

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

Interventions

Notch signaling pathway inhibitor MK0752 DRUG

gemcitabine hydrochloride DRUG

imaging biomarker analysis OTHER

laboratory biomarker analysis OTHER

pharmacological study OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * 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 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (5)

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

Barts and the London School of Medicine

London, England, EC1M 6BQ, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

St James' Hospital

Leeds, L59 7TF, United Kingdom

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Duncan Jodrell, MD

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2010
• First Posted: April 2, 2010
• Study Start: April 1, 2010
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

GB (5)