Pancreatic Cancer
Conditions
Keywords
stage IV pancreatic cancer, adenocarcinoma of the pancreas, recurrent pancreatic cancer
Brief summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with metastatic pancreatic cancer that did not respond to previous treatment with gemcitabine.
Detailed description
OBJECTIVES: Primary * Evaluate the 6-month overall survival rate in patients with gemcitabine hydrochloride-refractory metastatic pancreatic cancer treated with bevacizumab and erlotinib hydrochloride. * Determine the safety and toxicity of this regimen in these patients. Secondary * Evaluate the objective response rate in these patients. * Evaluate time to tumor progression in these patients. * Determine the efficacy of this regimen, in terms of the proportion of patients with ≥ 50% decline in carbohydrate antigen 19-9, also called cancer antigen 19-9 (CA19-9) biomarker, in these patients. * Obtain sequential measurements of circulating tumor cells (micrometastases) and endothelial cells in serum and correlate these variables with clinical outcomes (in patients enrolled in UCSF site only). OUTLINE: This is an open-label, nonrandomized, multicenter study. Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection at baseline and periodically during study for biomarker/laboratory analysis, including the CA19-9 biomarker. Circulating tumor micrometastases and endothelial cells are also measured in patients enrolled in University of California San Francisco (UCSF) site. After completion of study treatment, patients are followed at 30 days and at 6 months. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Interventions
BIOLOGICALbevacizumab
DRUGerlotinib hydrochloride
OTHERlaboratory biomarker analysis
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed adenocarcinoma of the pancreas * Documented extrapancreatic metastases * Radiographically measurable disease not required * Gemcitabine hydrochloride-refractory disease * Has undergone 1-3 prior therapies for locally advanced or metastatic disease with ≥ 1 regimen containing gemcitabine hydrochloride (alone or in combination with other agents) * Treatment given in the adjuvant setting (radiotherapy and/or chemotherapy, given either concurrently or systemically) does not count as prior therapy as long as progressive disease occurs \> 6 months after completion of treatment * No central nervous system (CNS) or brain metastases PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * International Normalized Ratio (INR) ≤ 1.5 (except in patients receiving full-dose warfarin) * Bilirubin ≤ 2.0 mg/dL * Creatinine ≤ 2.0 mg/dL * AST or ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if documented liver metastases) * Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed) * No contact lense use during and for 14 days after completion of study treatment * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment * No history of other disease, metabolic dysfunction, or physical examination or clinical laboratory finding that contraindicates use of an investigational drug or precludes study compliance * No history of serious systemic disease, including any of the following: * Myocardial infarction within the past 6 months * Stroke within the past 6 months * Uncontrolled hypertension (i.e., blood pressure \> 150/100 mm Hg on medication) * Unstable angina * New York Heart Association class II-IV congestive heart failure * Unstable symptomatic arrhythmia requiring medication * Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed * Peripheral vascular disease ≥ grade 2 * No significant traumatic injury within the past 28 days * No proteinuria (defined as urine protein:creatinine ratio ≥ 1.0 at screening) * No clinically significant impairment of renal function * No serious, nonhealing wound, ulcer, or bone fracture * No evidence of bleeding diathesis or coagulopathy * No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months PRIOR CONCURRENT THERAPY: * More than 28 days since prior major surgery or open biopsy * More than 7 days since prior fine-needle aspiration or core biopsy * No prior antiangiogenesis agent (e.g., bevacizumab or an oral vascular endothelial growth factor receptor small molecule inhibitor) given together with an agent that disrupts epidermal growth factor receptor signaling (e.g., cetuximab or erlotinib hydrochloride) for locally advanced or metastatic pancreatic cancer * Prior treatment with either one of the above alone allowed * More than 4 weeks since prior and no concurrent participation in another clinical trial * No other concurrent antineoplastic or antitumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy * No concurrent major surgery * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate at 6 Months | 6 months | Number of participants alive at 6 months |
| Safety and Toxicity | 21 weeks | Treatment associated toxicities. Adverse event assessments were performed on day 1 of each treatment cycle and at the end of treatment; the longest duration of treatment was 7 cycles (x 3 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response as Measured by RECIST Criteria | 21 weeks | Participants experiencing objecting response, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Time to Tumor Progression | from initial therapy to the first objective documentation of tumor progression | Time to tumor progression (TTP) was defined as the time from initial therapy to the first objective documentation of tumor progression (for patients with measurable disease) or to the data of death, if death was ascribed to progression of disease. |
| Proportion of Patients With ≥ 25% Decline in Serum CA19-9 Biomarker | 21 weeks | — |
Countries
United States
Participant flow
Recruitment details
Patients were recruited at a single U.S. clinical site between March 2006 and December 2008
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab Plus Erlotinib Patients received bevacizumab 15 mg/kg as a 60-90 minute infusion every 21 days (representing one treatment cycle) and erlotinib 150 mg by mouth daily | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Bevacizumab Plus Erlotinib |
|---|---|
| Age, Continuous | 60 years |
| Number of prior lines of systemic therapy 1 Prior Line of Therapy | 24 Participants |
| Number of prior lines of systemic therapy 2 Prior Lines of Therapy | 9 Participants |
| Number of prior lines of systemic therapy 3 Prior Lines of Therapy | 3 Participants |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 36 |
| serious Total, serious adverse events | 10 / 36 |
Outcome results
Primary
Overall Survival Rate at 6 Months
Number of participants alive at 6 months
Time frame: 6 months
Population: All participants were followed for survival
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab Plus Erlotinib | Overall Survival Rate at 6 Months | 8 participants |
Primary
Safety and Toxicity
Treatment associated toxicities. Adverse event assessments were performed on day 1 of each treatment cycle and at the end of treatment; the longest duration of treatment was 7 cycles (x 3 weeks)
Time frame: 21 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab Plus Erlotinib | Safety and Toxicity | Rash (Grades 1-3) | 26 participants |
| Bevacizumab Plus Erlotinib | Safety and Toxicity | Diarrhea (Grades 1-3) | 9 participants |
| Bevacizumab Plus Erlotinib | Safety and Toxicity | Hypertension (grade 3) | 4 participants |
| Bevacizumab Plus Erlotinib | Safety and Toxicity | Gastrointestinal Bleeding (Grades 1 & 3) | 2 participants |
| Bevacizumab Plus Erlotinib | Safety and Toxicity | Venous thromboembolic events (Grades 2-3) | 3 participants |
| Bevacizumab Plus Erlotinib | Safety and Toxicity | Pulmonary embolism | 2 participants |
| Bevacizumab Plus Erlotinib | Safety and Toxicity | Pancratogastic fistula | 1 participants |
| Bevacizumab Plus Erlotinib | Safety and Toxicity | Suspected hemorrhage into intrapulmonic metastases | 1 participants |
Secondary
Objective Response as Measured by RECIST Criteria
Participants experiencing objecting response, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 21 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab Plus Erlotinib | Objective Response as Measured by RECIST Criteria | 1 participants |
Secondary
Proportion of Patients With ≥ 25% Decline in Serum CA19-9 Biomarker
Time frame: 21 weeks
Population: Only patients with an elevated baseline CA19-9 (\>2x ULN) were included in this analysis (n = 26).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab Plus Erlotinib | Proportion of Patients With ≥ 25% Decline in Serum CA19-9 Biomarker | 4 Participants |
Secondary
Time to Tumor Progression
Time to tumor progression (TTP) was defined as the time from initial therapy to the first objective documentation of tumor progression (for patients with measurable disease) or to the data of death, if death was ascribed to progression of disease.
Time frame: from initial therapy to the first objective documentation of tumor progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab Plus Erlotinib | Time to Tumor Progression | 40 Days |