Clinical trial NCT00536874: Gemcitabine and Oxaliplatin in Treating Patients With Pancreatic Cancer That Can Be Removed By Surgery
Official title: A Phase II Study of Neoadjuvant Gemcitabine and Oxaliplatin in Patients With Potentially Resectable Previously Untreated Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-09-28
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall Survival at 18 Months
timeFrame: 18 months
Secondary outcomes:
measure: Overall Survival (Follow-Up Time)
timeFrame: From Baseline until 2 Years and Follow-Up, up to 120 months
measure: Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy
timeFrame: Baseline and 2 years
measure: RECIST Radiologic Response to Neoadjuvant Therapy
timeFrame: 2 years
measure: Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy
timeFrame: Baseline and 2 years
measure: Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy
timeFrame: Baseline and 2 years
measure: Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy
timeFrame: Baseline and 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Eileen O'Reilly, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Peter J. Allen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: O'Reilly EM, Perelshteyn A, Jarnagin WR, Schattner M, Gerdes H, Capanu M, Tang LH, LaValle J, Winston C, DeMatteo RP, D'Angelica M, Kurtz RC, Abou-Alfa GK, Klimstra DS, Lowery MA, Brennan MF, Coit DG, Reidy DL, Kingham TP, Allen PJ. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann Surg. 2014 Jul;260(1):142-8. doi: 10.1097/SLA.0000000000000251.