Pancreatic Cancer
Conditions
Keywords
adenocarcinoma of the pancreas, stage IA pancreatic cancer, stage IB pancreatic cancer, stage IIA pancreatic cancer, stage IIB pancreatic cancer, stage III pancreatic cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving gemcitabine together with oxaliplatin works in treating patients with pancreatic cancer that can be removed by surgery.
Detailed description
OBJECTIVES: Primary * To determine the overall 18-month survival of patients with radiographically resectable pancreatic adenocarcinoma treated with neoadjuvant gemcitabine and oxaliplatin followed by surgical resection and adjuvant gemcitabine. Secondary * To determine the safety, toxicity, and feasibility of this regimen in the neoadjuvant setting. * To determine the feasibility of obtaining preoperative core tissue biopsies and the ability to use these biopsies to establish pathologic correlates of response following neoadjuvant therapy and to determine if xenografts can be developed from these core tissues. * To determine the specific tumor marker response (CEA and CA19-9) to neoadjuvant therapy. * To determine the prognostic accuracy of serum protein profiles in these patients. * To determine the overall survival and patterns of tumor recurrence (local vs distant). OUTLINE: * Neoadjuvant therapy: Patients receive gemcitabine IV over 100 minutes and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. * Surgery: Within 2-6 weeks after completion of neoadjuvant therapy, patients undergo a laparoscopy that includes a pancreaticoduodenectomy or distal pancreatectomy with or without splenectomy. * Adjuvant therapy: Beginning 4-16 weeks after surgery, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor tissue and blood sample collection periodically for correlative studies. Samples are analyzed for protein expression and tumor markers (CEA and CA19-9) pre- and post-neoadjuvant therapy via proteomic analysis. Tumor tissue samples are also banked for research purposes. After completion of study treatment, patients are followed every 3 months.
Interventions
DRUGgemcitabine hydrochloride
1,000 mg/m2 IV over 100 minutes on day 1 every 14 days for 4 cycles
DRUGoxaliplatin
80 mg/m2 IV over 2 hours on day 1 every 14 days for 4 cycles.
GENETICprotein expression analysis
GENETICproteomic profiling
OTHERdiagnostic laboratory biomarker analysis
PROCEDUREadjuvant therapy
PROCEDUREneoadjuvant therapy
PROCEDUREtherapeutic conventional surgery
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
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
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed pancreatic adenocarcinoma * No histology other than adenocarcinoma (e.g., neuroendocrine cancer or acinar cancer) * Patients with adenosquamous variants are eligible * Radiographically resectable pancreatic cancer, as determined by a surgical oncologist * No metastatic or locally unresectable pancreatic adenocarcinoma * No evidence of distant metastases by CT scan * Negative or pending laparoscopy for distant metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ 4.0 mg/dL (if \> 3.0, stented and known to be declining) * Serum creatinine ≤ 1.6 mg/dL * INR \< 1.5 (therapeutic INR is allowed for patients receiving therapeutic anticoagulation) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study therapy * No active infection, except for resolving cholangitis, that would preclude study enrollment * Neoadjuvant therapy may only be initiated when acute cholangitis has resolved * No other malignancy within the past 3 years except for curatively treated basal cell carcinoma of the skin, cervical intraepithelial neoplasia, or localized prostate cancer with a PSA of \< 5.0 ng/mL within ≥ 4 weeks of study entry (other circumstances with a recent concurrent or active malignancy will be adjudicated on a case-by-case basis by the principle investigator \[PI\] or co-PI) * No known hypersensitivity to any of the components of oxaliplatin or gemcitabine * No hypersensitivity to CT scan IV contrast dye not suitable for premedication * No peripheral neuropathy ≥ grade 2 * No known HIV or hepatitis B or C infection (active, previously treated, or both) * No other medical condition, including mental illness or substance abuse that, deemed by the investigator, would preclude study participation PRIOR CONCURRENT THERAPY: * More than 4 weeks since prior radiotherapy * No prior radiotherapy to \> 25% of bone marrow * More than 30 days since prior and no other concurrent investigational therapy * No other prior therapy for pancreatic cancer * No other concurrent chemotherapy, immunotherapy, or radiotherapy during neoadjuvant therapy * Concurrent low molecular weight heparin or warfarin, where medically indicated, allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at 18 Months | 18 months | Percentage of participants that were alive or survived at 18 months after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (Follow-Up Time) | From Baseline until 2 Years and Follow-Up, up to 120 months | — |
| Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy | Baseline and 2 years | — |
| RECIST Radiologic Response to Neoadjuvant Therapy | 2 years | 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 |
| Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy | Baseline and 2 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine And Oxaliplatin A Phase II Study of Neoadjuvant Gemcitabine And Oxaliplatin In Patients With Potentially Resectable Previously Untreated Pancreatic Adenocarcinoma
gemcitabine hydrochloride: 1,000 mg/m2 IV over 100 minutes on day 1 every 14 days for 4 cycles
oxaliplatin: 80 mg/m2 IV over 2 hours on day 1 every 14 days for 4 cycles.
protein expression analysis
proteomic profiling
diagnostic laboratory biomarker analysis
adjuvant therapy
neoadjuvant therapy
therapeutic conventional surgery | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gemcitabine And Oxaliplatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 26 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 63.5 years STANDARD_DEVIATION 33.23401872 |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 39 |
| serious Total, serious adverse events | 25 / 39 |
Outcome results
Primary
Overall Survival at 18 Months
Percentage of participants that were alive or survived at 18 months after randomization
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine And Oxaliplatin | Overall Survival at 18 Months | 63 percentage of participants |
Secondary
Overall Survival (Follow-Up Time)
Time frame: From Baseline until 2 Years and Follow-Up, up to 120 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine And Oxaliplatin | Overall Survival (Follow-Up Time) | 39.6 months |
Secondary
RECIST Radiologic Response to Neoadjuvant Therapy
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: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine And Oxaliplatin | RECIST Radiologic Response to Neoadjuvant Therapy | Partial Response | 4 participants |
| Gemcitabine And Oxaliplatin | RECIST Radiologic Response to Neoadjuvant Therapy | Stable Disease | 28 participants |
| Gemcitabine And Oxaliplatin | RECIST Radiologic Response to Neoadjuvant Therapy | Progression of Disease | 3 participants |
| Gemcitabine And Oxaliplatin | RECIST Radiologic Response to Neoadjuvant Therapy | Inevaluable | 3 participants |
Secondary
Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy
Time frame: Baseline and 2 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Gemcitabine And Oxaliplatin | Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy | Ca 19-9 (Pre-Therapy) | 133 U/ml |
| Gemcitabine And Oxaliplatin | Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy | Ca 19-9 (Post-Therapy) | 132 U/ml |
Secondary
Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy
Percent change in specific tumor marker (Cancer Antigen 19-9, Ca 19-9) levels in response to neoadjuvant therapy
Time frame: Baseline and 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine And Oxaliplatin | Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy | -25.6 percent change |
Secondary
Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy
Time frame: Baseline and 2 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Gemcitabine And Oxaliplatin | Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy | CEA (Pre-Therapy) | 4.2 ng/ml |
| Gemcitabine And Oxaliplatin | Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy | CEA (Post-Therapy) | 4.2 ng/ml |
Secondary
Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy
Percentage change in specific tumor marker (Carcinoembryonic antigen, CEA) levels in response to neoadjuvant therapy
Time frame: Baseline and 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine And Oxaliplatin | Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy | -5.1 percent change |