Lapatinib Ditosylate and Capecitabine in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Basic Trial Information
|Phase II||Treatment||18 and over||2008-437|
This phase II trial studies how well lapatinib ditosylate and capecitabine works in treating patients with locally advanced or metastatic pancreatic cancer. 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.
Further Study Information
I. To assess the efficacy of lapatinib (lapatinib ditosylate) and capecitabine as 2nd line therapy in metastatic pancreatic cancer in terms of overall survival.
I. To assess secondary efficacy endpoints of the regimen including clinical benefit response, progression free survival, and objective response rate.
II. To evaluate the toxicity of the combination of lapatinib and capecitabine in the pancreatic cancer patient population.
III. To identify intratumoral biomarkers which correlate with or are predictive of clinical outcome, including expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2), phosphorylated mitogen activated protein kinase (MAPK), phosphorylated extracellular-signal-regulated kinase (ERK), signal transducer and activator of transcription 5 (STAT5), AKT3, and KRAS, phosphatidylinositol 3' -kinase (PI3K) mutation analysis.
IV. To explore the usage of circulating tumor cells (CTC) in predicting clinical response of pancreatic cancer to chemotherapy.
V. Together with the companion exploratory protocol, assess the feasibility of propagating human tumor from biopsy implanted in nude mice and isolating pancreas stem cells.
Patients receive lapatinib ditosylate orally (PO) on days 1-21 and capecitabine PO twice daily (BID) on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 6 months.
Platelets >= 100,000/m^3
Histologically confirmed adenocarcinoma of the pancreas
Radiographically measurable disease
Must either be able to swallow and/or receive enteral medication via gastrostomy feeding tumor (subjects who are nulla per os [NPO] will only be deemed eligible after approval by the Principal Investigator)
Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram (multigated acquisition [MUGA] scan may be performed if echocardiogram [ECHO] is not available)
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Signed informed consent form
Absolute neutrophil count (ANC) >= 1500/mm^3
Serum total bilirubin =< 1.5 x upper limit of normal (ULN)
Aspartate aminotransaminase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN unless liver metastases are present, in which case =< 5.0 x ULN
Creatinine clearance >= 30 mL/min
Ejection fraction > 50% (based on 2-dimensional (2-D) ECHO or MUGA scan)
Prior failed 1st line gemcitabine therapy for metastatic disease, or relapsed within six months since completion of gemcitabine adjuvant therapy; failure is defined as radiological or clinical progression or documented unacceptable toxicity
Prior capecitabine or 5FU is allowed (but not required) in the setting of radiation
Patients have not recovered from adverse events to a toxicity grade =< 1 due to prior chemotherapy
Human immunodeficiency virus (HIV) positive patients on antiretroviral therapy (to avoid potential for drug interactions)
Creatinine clearance < 30 mL/min as calculated by the Cockroft-Gault equation
ANC < 1500
History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or capecitabine
Any prior treatment with lapatinib, or any anti-HER2 treatment or any anti-EGFR treatment
More than one prior chemotherapy regimen
Patients with known brain metastases, uncontrolled seizure disorders, encephalitis, or multiple sclerosis will be excluded from this clinical trial because of their poor prognosis or because they often develop progressive neurological dysfunction that would confound the evaluation of other adverse events
Women who are pregnant or lactating; women and men of child-bearing potential who are not using a reliable form of contraception
Malabsorption syndrome or uncontrolled inflammatory gastrointestinal (GI) disease (Crohn's or ulcerative colitis)
Known history of uncontrolled or symptomatic angina, arrhythmia, or congestive heart failure (atrial fibrillation is allowed if the heart rate is under control)
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Concurrent malignancy (i.e., malignancy other than adenocarcinoma of the pancreas), unless
The subject has been curatively treated and disease free for >= 2 years, or
The cancer has non-melanoma skin cancer or early cervical cancer
Platelets < 75,000
Transaminases > 3.0 times the upper limit of normal (ULN), except in known hepatic metastasis, wherein they must be =< 5.0 x ULN
Total bilirubin > 1.5 times the ULN, > 2.5 x ULN if patient has Gilbert's syndrome
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
MedStar Georgetown University Hospital
- National Cancer Institute
District of Columbia
MedStar Georgetown University Hospital
Aiwu Ruth He
Aiwu Ruth He
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00881621
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.