Pancreatic Cancer
Conditions
Brief summary
The current trial will provide important data on the recurrence rates and patterns of failure using state of the art target agent, chemotherapy and proton beam technology for patients with Locally Advanced Pancreatic Cancer (LAPC). A median survival of 10 months or greater would be considered evidence of a regimen potentially worthy of further study as a new treatment paradigm in one arm in a future phase III trial.
Detailed description
The current trend toward using the biology of the disease as it becomes evident over a period of chemotherapy to better select patients who will benefit from chemoradiotherapy (CRT) seems to be the most pragmatic way to proceed, until we have a better means of predicting tumor behavior and more active systemic agents. This has led to increased interest in treatment regimens incorporating induction chemotherapy with target agent followed by CRT and additional chemotherapy for diseases that carry a high risk for systemic relapse. The PA.3 trial was the first phase III trial in advanced pancreatic cancer to show a survival advantage with the addition of a second drug, in this case the oral Epidermal growth factor receptor (EGFR) inhibitor Erlotinib to gemcitabine. The approval provides an important proof of concept regarding the use of newer targeted therapies in pancreatic cancer 7. Proton beam therapy may result in lower toxicity, enhanced efficacy and could contribute to improved local control of patients with LAPC. The capecitabine and oxaliplatin ((CapOx)) regimen utilized in this trial has been proven to be active in gemcitabine-pretreated patients with advanced pancreatic cancer. The current trial will provide important data on the recurrence rates and patterns of failure using state of the art target agent, chemotherapy and proton beam technology for patients with LPAC. A median survival of 10 months or greater would be considered evidence of a regimen potentially worthy of further study as a new treatment paradigm in one arm in a future phase III trial. Patients with unresectable or borderline resectable non-metastatic adenocarcinoma of the pancreas, as defined by 2012 National Comprehensive Cancer Network (NCCN) guidelines, were included. Patients received neoadjuvant gemcitabine 1000 mg/m2 IV on days 1, 8, 15, 22, 29, 36, and 43 and erlotinib 100 mg by mouth every day for 1-43 days (GE). If there was no evidence of metastatic disease after GE, then patients preceded with proton therapy to 50.4 Gy in 28 fractions with concurrent capecitabine 825 mg/m2 twice per day (PCT). This was followed with maintenance oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice per day on days 2 to 15 (CapOx) for 4 cycles. The primary study objective was 1-year overall survival (OS). The benchmark was 43% 1-year survival as demonstrated in Radiation Therapy Oncology Group (RTOG/NRG) 98- 12. The Kaplan-Meier method was used to estimate the one-year OS and the median OS and progression-free survival (PFS).
Interventions
RADIATIONProton, Gemcitabine, Erlotinib, Capecitabine
Gemcitabine 1000 mg/m2 iv, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43 Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed. Post-proton chemotherapy: To be started in 4 to 6 weeks after completion of proton chemotherapy. Oxaliplatin 130 mg/m2 po bid on days 2 to 15 for 14 days. The CapOx regimen (Capcitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles.
RADIATIONProton Radiation
Sponsors
Loma Linda 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 or cytologically confirmed unresectable non-metastatic adenocarcinoma of the pancreas * The American Joint Committee on Cancer (AJCC) stage I-III with unresectable or borderline unresectable disease as defined by NCCN guidelines * Radiological resectability is defined by the following criteria on abdominal imaging: 1. No evidence of tumor extension to the celiac axis, hepatic artery or superior mesenteric artery. 2. No evidence of tumor encasement or occlusion of the superior mesenteric vein (SMV) or the SMV/portal vein confluence 3. No evidence of visceral or peritoneal metastases * Borderline and Unresectable cases would be defined as those that do not meet the criteria in section and also show no evidence of distant metastatic or intraperitoneal disease. * Eastern Cooperative Oncology Group performance status of ≤ 2 * Age \> 18 years * Adequate hematologic reserve, hepatic reserve and renal function * White Blood Cell (WBC) \> 2,000 cells/mm3 * Absolute Neutrophil Count (ANC) \> 1,500 cells/mm3 * Platelets \> 100,000 cells/mm3 * Serum bilirubin ≤ 2.5 mg/dL * Serum creatinine ≤ 2 x upper limit of normal (ULN), or creatinine clearance (Ccr) ≥ 30ml/min * Alanine aminotransferase (ALT) \< 3 times ULN * Aspartate transaminase (AST) \< 3 times ULN * Albumin \> 3.2 g/dl * Patient must sign study-specific informed consent
Exclusion criteria
* AJCC stage IV with metastatic disease * Eastern Cooperative Oncology Group performance status of \> 2 * Age \< 18 years * WBC \< 2,000 cells/mm3 * ANC \< 1,500 cells/mm3 * Platelets \> 100,000 cells/mm3 * Serum bilirubin \> 2.5 mg/dL * Serum creatinine \> 2 x upper limit of normal (ULN), or creatinine clearance (Ccr) ≥ 30ml/min * ALT \> 3 times ULN * AST \> 3 times ULN * Albumin \< 3.2 g/dl
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One-year Survival Rate | One year after treatment completed. | Subjects will be followed after treatment completed to determine length of survival rate. The primary study objective was 1-year overall survival (OS, failure: death due to any cause). The Kaplan-Meier method was used to estimate the one-year OS. Secondary Objectives were the frequency of serious adverse events, disease control rate and progression-free survival. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Proton Radiation Radiation: Proton, Gemcitabine, Erlotinib, Capecitabine Gemcitabine 1000 mg/m2 iv, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43 Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed.
Post-proton chemotherapy: To be started in 4 to 6 weeks after completion of proton chemotherapy. Oxaliplatin 130 mg/m2 po bid on days 2 to 15 for 14 days. The CapOx regimen (Capcitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles.
Radiation: Proton Radiation | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Proton Radiation |
|---|---|
| Age, Continuous | 59.6 years |
| Proton Radiation | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 9 |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 9 / 9 |
Outcome results
Primary
One-year Survival Rate
Subjects will be followed after treatment completed to determine length of survival rate. The primary study objective was 1-year overall survival (OS, failure: death due to any cause). The Kaplan-Meier method was used to estimate the one-year OS. Secondary Objectives were the frequency of serious adverse events, disease control rate and progression-free survival.
Time frame: One year after treatment completed.
Population: The study enrolled 9 patients between January 2013 and March 2016, when the trial was closed due to poor accrual.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Proton Radiation | One-year Survival Rate | 55.6 percentage of participants |
Comparison: In the RTOG 9812 (NCT00003591) for unresectable pancreatic cancer, a one-year survival rate of 43% was observed. There were 109 analyzable patients on NCT00003591 with 61 still at risk for death at one year. Using the method of Dixon and Simon, a sample size of 39 analyzable patients followed over 12 months will ensure at least 90% probability of detecting a minimum of 17% improvement in the one-year survival rate compared to NCT00003591 at the 0.10 significance level (with a one-sided test).p-value: 0.1t-test, 1 sided