Pancreatic Cancer
Conditions
Keywords
recurrent pancreatic cancer, stage III pancreatic cancer, stage IV pancreatic cancer, adenocarcinoma of the pancreas
Brief summary
RATIONALE: Sorafenib and erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving sorafenib together with erlotinib works in treating patients with pancreatic cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES: Primary * To determine the efficacy of sorafenib tosylate in combination with erlotinib hydrochloride in patients with unresectable pancreatic cancer. Secondary * To determine the response rate in patients treated with this regimen. * To determine the progression-free survival of patients treated with this regimen at 4 months. * To evaluate the safety profile of this regimen in these patients. * To evaluate the change in serum Ca 19-9 levels at baseline and at 8-week intervals. * To evaluate the plasma proteomic profile at baseline and at 8 weeks to correlate with clinical parameters in order to identify potential prognostic or predictive markers. * To analyze single-nucleotide polymorphisms on DNA obtained from pretreatment blood samples to evaluate toxicity and response to erlotinib hydrochloride. OUTLINE: Patients receive oral sorafenib tosylate once or twice daily and oral erlotinib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Serum samples are collected at baseline and at 8-week intervals to measure Ca 19-9 levels, and plasma and buffy coat samples are collected at baseline and at week 8 for proteomic assessment and genotyping of single-nucleotide polymorphisms associated with response and toxicity to erlotinib hydrochloride. After completion of study treatment, patients are followed up every 3 months.
Interventions
DRUGSorafenib
400 mg taken by mouth 1 time per day.
DRUGErlotinb
150 mg taken by mouth 1 time per day.
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Microscopically confirmed diagnosis of pancreatic adenocarcinoma * Unresectable disease * No neuroendocrine tumors or cystadenocarcinoma * Measurable or evaluable disease by RECIST criteria * No known brain metastases * Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement) * Creatinine ≤ 1.5 times ULN * INR \< 1.5 or PT/PTT normal unless patients are receiving anticoagulation treatments * Negative pregnancy test * Not pregnant or nursing * Fertile patients must use effective barrier contraception before, during, and for at least 6 months after completion of study treatment * Able to swallow whole pills * No patients who currently smoke * No cardiac disease, including any of the following: * NYHA class III-IV congestive heart failure * Unstable angina (anginal symptoms at rest) * New-onset angina (began within the past 3 months) * Myocardial infarction within the past 6 months * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * No uncontrolled hypertension defined as systolic BP \> 150 mm Hg or diastolic BP \> 90 mm Hg despite optimal medical management * No arterial thrombotic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months * No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 in the past 4 weeks * No other hemorrhage/bleeding event ≥ CTCAE grade 3 in the past 4 weeks * No significant traumatic injury in the past 4 weeks * No known untreated malabsorption problem (e.g., ulcerative colitis, Crohn's disease) * No known HIV positivity or chronic hepatitis B or C * No known or suspected allergy to sorafenib tosylate or erlotinib hydrochloride * No active clinically serious infection \> CTCAE grade 2 * No serious non-healing wound, ulcer, or bone fracture * No evidence or history of bleeding diathesis or coagulopathy (except for cancer-related blood clots) * No dermatitis ≥ CTCAE grade 2 at baseline * No patients who currently smoke PRIOR CONCURRENT THERAPY: * No prior treatment with antiangiogenics (e.g., bevacizumab, thalidomide, marimastat, interferon alfa, vatalanib, vandetanib, ZD6126, sorafenib, semaxanib, sunitinib, axitinib) * No more than one line of prior therapy for metastatic disease * More than 4 weeks since prior major surgery or open biopsy * No concurrent strong CYP34A inhibitors or inducers * Concurrent warfarin or heparin allowed with the approval of the principal investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Progression-free Survival | at 8 weeks | Number of patients with progression-free survival at 8 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | at 4 months | Per RECIST criteria v. 1.0: measurable lesions: CR disappearance of target lesions, PR \> 30% decrease in the sum of the longest diameter (LD) of target lesions, PD \> 20% increase in the sum of the LD of target lesions or appearance of new lesions, SD neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions |
| Number of Patients With Progression-free Survival | at 4 months | Participants with progression-free survival at 4 months. |
| Number of Patients With Worst Grade Toxicities | every 4 weeks and every 8 weeks in follow-up to resolution of toxicity | Number of patients with worst-grade toxicity at each of five grades (grade 1 to 5, with 5 most severe) following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death. |
Countries
United States
Participant flow
Recruitment details
This study enrolled patients from October 2008 until February 2011.
Pre-assignment details
37 patients consented and went on study. Six patients were ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sorafenib + Erlotinib | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Death | 2 |
| Overall Study | disease progression | 24 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 1 |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 37 |
| serious Total, serious adverse events | 27 / 37 |
Outcome results
Primary
Number of Patients With Progression-free Survival
Number of patients with progression-free survival at 8 weeks
Time frame: at 8 weeks
Population: Patients who received treatment for \>= 8 weeks. 14 study patients were treated for \< 8 weeks due to toxicity (5), disease progression (5), did not receive study drug (1), respiratory failure (1), drug held more than 28 days (1), patient withdrawal (1). The remaining 13 participants did not have a progression-free survival at 8 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Number of Patients With Progression-free Survival | 10 participants |
Secondary
Number of Patients With Progression-free Survival
Participants with progression-free survival at 4 months.
Time frame: at 4 months
Population: Patients with progression-free survival at 4 months. The remaining 17 patients were not available for evaluation at 4 months due to toxicity (5), disease progression (5), patient withdrawal (1),respiratory failure (1), study drug held more than 28 days (1), and no study drug (1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Number of Patients With Progression-free Survival | 4 participants |
Secondary
Number of Patients With Worst Grade Toxicities
Number of patients with worst-grade toxicity at each of five grades (grade 1 to 5, with 5 most severe) following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death.
Time frame: every 4 weeks and every 8 weeks in follow-up to resolution of toxicity
Population: All patients who received treatment with the study drugs. One patient did not receive treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Number of Patients With Worst Grade Toxicities | number of patients with worst grade toxicity - 1 | 1 participants |
| Treatment | Number of Patients With Worst Grade Toxicities | number of patients with worst grade toxicity - 2 | 5 participants |
| Treatment | Number of Patients With Worst Grade Toxicities | number of patients with worst grade toxicity - 3 | 26 participants |
| Treatment | Number of Patients With Worst Grade Toxicities | number of patients with worst grade toxicity - 4 | 3 participants |
| Treatment | Number of Patients With Worst Grade Toxicities | number of patients with worst grade toxicity - 5 | 1 participants |
Secondary
Response Rate
Per RECIST criteria v. 1.0: measurable lesions: CR disappearance of target lesions, PR \> 30% decrease in the sum of the longest diameter (LD) of target lesions, PD \> 20% increase in the sum of the LD of target lesions or appearance of new lesions, SD neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
Time frame: at 4 months
Population: Participants who received treatment for 4 or more months. The remaining 10 participants received treatment for less than 4 months and were not evaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Response Rate | Complete Response | 0 participants |
| Treatment | Response Rate | Partial Response | 0 participants |
| Treatment | Response Rate | Stable Disease | 8 participants |
| Treatment | Response Rate | Progressive Disease | 19 participants |