Lapatinib Ditosylate and Capecitabine in Treating Patients With Metastatic Pancreatic Cancer
Primary Purpose
Pancreatic Cancer
Status
Completed
Phase
Phase 2
Locations
Ireland
Study Type
Interventional
Intervention
capecitabine
lapatinib ditosylate
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring adenocarcinoma of the pancreas, recurrent pancreatic cancer, stage IV pancreatic cancer
Eligibility 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
Sites / Locations
- Cork University Hospital
- Mercy University Hospital
- Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
- St. Vincent's University Hospital
- Mater Misericordiae University Hospital
- Mater Private Hospital
- St. James's Hospital
- Beaumont Hospital
- University College Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Capecitabine and Lapatinib
Arm Description
Outcomes
Primary Outcome Measures
6-month survival rate
Secondary Outcome Measures
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.
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.
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.
Safety and tolerability
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.
Full Information
NCT ID
NCT00962312
First Posted
August 19, 2009
Last Updated
December 30, 2014
Sponsor
Cancer Trials Ireland
1. Study Identification
Unique Protocol Identification Number
NCT00962312
Brief Title
Lapatinib Ditosylate and Capecitabine in Treating Patients With Metastatic Pancreatic Cancer
Official Title
A Phase II Study of Lapatinib and Capecitabine in the Treatment of Metastatic Pancreatic Cancer.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cancer Trials Ireland
4. Oversight
5. Study Description
Brief Summary
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
adenocarcinoma of the pancreas, recurrent pancreatic cancer, stage IV pancreatic cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Capecitabine and Lapatinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
capecitabine
Intervention Type
Drug
Intervention Name(s)
lapatinib ditosylate
Primary Outcome Measure Information:
Title
6-month survival rate
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
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.
Time Frame
6 months
Title
Overall response rate
Description
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.
Time Frame
up to 6 months
Title
Clinical benefit
Description
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.
Time Frame
6 months
Title
Safety and tolerability
Time Frame
Throughout course of study
Title
Tumour biomarker analysis
Description
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.
Time Frame
Currently ongoing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ray McDermott, MD
Organizational Affiliation
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cork University Hospital
City
Cork
Country
Ireland
Facility Name
Mercy University Hospital
City
Cork
Country
Ireland
Facility Name
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
City
Dublin
ZIP/Postal Code
24
Country
Ireland
Facility Name
St. Vincent's University Hospital
City
Dublin
ZIP/Postal Code
4
Country
Ireland
Facility Name
Mater Misericordiae University Hospital
City
Dublin
ZIP/Postal Code
7
Country
Ireland
Facility Name
Mater Private Hospital
City
Dublin
ZIP/Postal Code
7
Country
Ireland
Facility Name
St. James's Hospital
City
Dublin
ZIP/Postal Code
8
Country
Ireland
Facility Name
Beaumont Hospital
City
Dublin
ZIP/Postal Code
9
Country
Ireland
Facility Name
University College Hospital
City
Galway
Country
Ireland
12. IPD Sharing Statement
Learn more about this trial
Lapatinib Ditosylate and Capecitabine in Treating Patients With Metastatic Pancreatic Cancer
We'll reach out to this number within 24 hrs