Pancreas Cancer
Conditions
Keywords
Pancreas cancer, lapatinib, capecitabine
Brief summary
Patients are being asked to participate in this study who have locally advanced or metastatic pancreatic cancer (cancer of the pancreas that has spread to another part of the body) that has gotten worse after first-line chemotherapy. The purpose of this study is to see if the drugs, Capecitabine and Lapatinib (two chemotherapy agents), prolong survival and improve quality of life as compared to supportive care alone. Lapatinib in combination with a drug called capecitabine, has been approved by the Food and Drug Administration (FDA) for the treatment of metastatic breast cancer. It has not yet been approved to treat this type of cancer. Both of these drugs are pills. This research is being done because it is not known if the combination of Capecitabine and Lapatinib is better than supportive care alone for pancreatic cancer.
Detailed description
This is an open-label single-arm Phase II trial for patients with metastatic pancreatic cancer who have failed first line Gemcitabine-based therapy. Patients will be treated with a combination of Capecitabine and Lapatinib, a dual tyrosine-kinase inhibitor of EGFR and HER-2.
Interventions
Lapatinib 1250-mg PO daily one hour before or after meals Capecitabine 1000 mg/m2 PO twice daily on days 1-14 of 21-day cycle for a total of 8 cycles
Sponsors
GlaxoSmithKline
Georgetown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed adenocarcinoma of the pancreas * Prior failed 1st line gemcitabine therapy for metastatic disease or relapsed within six months of completion of gemcitabine adjuvant therapy * Prior capecitabine or 5fu is allowed in the setting of radiation * Must either be able to swallow or receive enteral nutrition via gastrostomy feeding tube * Cardiac ejection fraction within institutional range of normal as measured by echocardiogram * ECOG performance status 0-2 * Signed informed consent form * Adequate hepatic, bone marrow, and renal function
Exclusion criteria
* Any prior treatment with lapatinib, or any anti-HER2 treatment or any anti-EGFR treatment * Not recovered from adverse events to a toxicity grade \</= 1 due to prior chemotherapy * More than one prior chemotherapy regimens * Known brain metastases, uncontrolled seizure disorders, encephalitis, or multiple sclerosis * HIV positive on antiretroviral therapy * Pregnant or lactating * History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or capecitabine * Malabsorption syndrome or uncontrolled inflammatory GI disease (Crohn's or ulcerative colitis) * Known history of uncontrolled or symptomatic angina, arrhythmia, or congestive heart failure * 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 deficiency * Concurrent malignancy unless the subject has been curatively treated and disease free for \>/= 2 years or the cancer was non-melanoma skin cancer or early cervical cancer. * Creatinine clearance \< 30 mL/min * Absolute neutrophil count \< 1500, platelets \< 75,000 * Transaminases \> 3.0 times the upper limit of normal, except in known hepatic metastasis, wherein they must be \< 5.0 times the upper limit of normal * Total bilirubin \> 1.5 times the ULN, \> 2.5 x ULN if patient has Gilbert's syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 24 months | Time of study entry to time of death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Response | 3 months | number of participants who had stable disease or partial response or complete response per Response Evaluation Criteria In Solid Tumors. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Progression Free Survival | 24 months | Time of study entry to cancer progression. |
| Adverse Events | 2 years | Grade 3 or 4 toxicities |
Countries
United States
Participant flow
Recruitment details
Due to change of practice, it is difficult to complete the enrollment for the study
Participants by arm
| Arm | Count |
|---|---|
| Lapatinib and Capecitabine Treatment
Lapatinib and Capecitabine: Lapatinib 1250-mg PO daily one hour before or after meals Capecitabine 1000 mg/m2 PO twice daily on days 1-14 of 21-day cycle for a total of 8 cycles | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 34 |
Baseline characteristics
| Characteristic | Lapatinib and Capecitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| ECOG ECOG PS 0 | 3 participants |
| ECOG ECOG PS 1 | 12 participants |
| ECOG ECOG PS2 | 2 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 5 / 17 |
Outcome results
Primary
Overall Survival
Time of study entry to time of death
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lapatinib and Capecitabine | Overall Survival | 5.2 months |
Secondary
Adverse Events
Grade 3 or 4 toxicities
Time frame: 2 years
Population: grade 3 or 4 toxicities
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib and Capecitabine | Adverse Events | 3 participants |
Secondary
Clinical Benefit Response
number of participants who had stable disease or partial response or complete response per Response Evaluation Criteria In Solid Tumors. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib and Capecitabine | Clinical Benefit Response | 6 participants |
Secondary
Progression Free Survival
Time of study entry to cancer progression.
Time frame: 24 months
Population: Time of study entry to disease progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lapatinib and Capecitabine | Progression Free Survival | 2.6 months |