Lapatinib Ditosylate and Capecitabine in Treating Patients With Metastatic Pancreatic Cancer

Cancer Trials Ireland

Status and phase

Completed

Phase 2

Conditions

Pancreatic Cancer

Treatments

Drug: capecitabine

Drug: lapatinib ditosylate

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00962312

EU-20933

ICORG-08-39

08-39 ICORG

EUDRACT-2008-006907-22

Details and patient eligibility

About

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.

Full description

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.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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