Lapatinib Ditosylate And Capecitabine In Treating Patients With Metastatic Pancreatic Cancer

Study Overview

Lapatinib Ditosylate and Capecitabine in Treating Patients With Metastatic Pancreatic Cancer

RATIONALE: Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib ditosylate together with capecitabine may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving lapatinib ditosylate together with capecitabine works in treating patients with metastatic pancreatic cancer.

OBJECTIVES: Primary * To evaluate the efficacy of lapatinib ditosylate and capecitabine as first-line therapy, in terms of overall survival, in patients with metastatic pancreatic cancer. Secondary * To evaluate the progression-free survival of patients treated with this regimen. * To evaluate the overall response rate (complete and partial responses) in patients treated with this regimen. * To evaluate the clinical benefit (complete response, partial response, or stable disease for ≥ 6 months) of this regimen in these patients. * To evaluate the qualitative and quantitative toxicity associated with this regimen in these patients. * To determine the intra-tumoral expression of ErbB1 (EGFR) and ErbB2 (HER2/neu) in these patients. * To seek pilot information on the intra-tumoral expression of markers of tumor resistance and sensitivity to treatment, including resistance drug pump expression and growth factor receptor expression. * To collect pre- and post-treatment serum samples from these patients for proteomic analyses to elucidate if any serum cancer marker profiles can be detected. OUTLINE: This is a multicenter study. Patients receive oral lapatinib ditosylate once daily on days 1-21 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-12 weeks.

Pancreatic Cancer

DRUG: capecitabine
DRUG: lapatinib ditosylate

08-39 ICORG
ICORG-08-39
EUDRACT-2008-006907-22
EU-20933

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 2009-08-19	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2014-12-30
First Submitted that Met QC Criteria 2009-08-19	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2014-12-31
First Posted (ESTIMATED) 2009-08-20	Results First Posted N/A	Last Verified 2012-10

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:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Capecitabine and Lapatinib	DRUG: capecitabine DRUG: lapatinib ditosylate

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Capecitabine and Lapatinib

DRUG: capecitabine

DRUG: lapatinib ditosylate

Primary Outcome Measures	Measure Description	Time Frame
6-month survival rate		6 months

Secondary Outcome Measures	Measure Description	Time Frame
Progression-free survival	Progression-free survival (PFS) will be measured as the number of days between patient's enrolment and his or her date of progression of disease. Patients who are still living six months after the last patient has been enrolled will be censored for the analyses, using the number of days between enrolment and the date of last follow-up. Disease progression will be determined according to definitions established in the modified response evaluation criteria in solid tumours (RECIST) (refer to Appendix G). For patients with non-measureable tumours disease progression will be determined by the treating physician in consultation with the Chief investigator for the study.	6 months
Overall response rate	The overall response rate will be an aggregation of the complete responses and partial responses. For patients to be given the status of complete response or partial response a confirmatory disease assessment should be performed no less than four weeks after the criteria for response are first met.	up to 6 months
Clinical benefit	A patient will be regarded as' having experienced clinical benefit if they have shown a complete response, a partial response, or stable disease for at least six months.	6 months
Safety and tolerability		Throughout course of study
Tumour biomarker analysis	Characterising the patient population by determination of intra-tumoural expression of ErbB1 (EGFR) and ErbB2 (Her2/neu).Seeking pilot information as to the intra-tumoural expression of markers of tumour resistance and sensitivity to treatment. Proteomic analysis of serum samples for potential markers.	Currently ongoing

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 metastatic adenocarcinoma of the pancreas
Measurable or non-measurable disease

Measurable disease is defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
No known brain metastases or leptomeningeal disease

ECOG performance status 0-1
Life expectancy > 12 weeks
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9 g/dL
Albumin ≥ 2.5 g/dL
Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) (2.5 times ULN if Gilbert's syndrome is present)
AST and ALT ≤ 3 times ULN (5 times ULN if documented liver metastases are present)
Creatinine < 1.5 times ULN
Cardiac ejection fraction normal by ECHO or MUGA scan
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Able to swallow and retain oral medication
No gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, requirement for IV alimentation, or uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
No active hepatic or biliary disease, except for Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment
No active cardiac disease within the past 6 months, including any of the following:

Uncontrolled angina
Clinically significant arrhythmia, except for asymptomatic atrial fibrillation requiring anticoagulation
Myocardial infarction
Uncontrolled or symptomatic congestive heart failure
Any other cardiac condition that, in the opinion of the treating physician, would make this study unreasonably hazardous for the patient
No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib ditosylate or any of its excipients, capecitabine, or fluorouracil
No known dihydropyrimidine dehydrogenase (DPD) deficiency
No other malignancy within the past 5 years except for completely resected nonmelanoma skin cancer or successfully treated in situ carcinoma

Recovered from prior radiotherapy or surgery
No prior surgical procedures affecting absorption
No prior EGFR- or ErbB2-targeting therapies
No prior capecitabine
No prior chemotherapy for locally advanced or metastatic pancreatic cancer
At least 3 months since prior adjuvant chemotherapy

Prior fluorouracil allowed as a radiosensitizer only
More than 30 days (or 5 half-lives) since prior investigational drugs
No concurrent radiotherapy or surgery for metastatic cancer
No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent CYP3A4 inducers or inhibitors
No other concurrent investigational agents or anticancer therapy (e.g., cytotoxic or biologic therapy)
No concurrent herbal (alternative) medicines

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Ray McDermott, MD, Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital

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