Gemcitabine and Oxaliplatin in Treating Patients With Pancreatic Cancer That Can Be Removed By Surgery

A Phase II Study of Neoadjuvant Gemcitabine and Oxaliplatin in Patients With Potentially Resectable Previously Untreated Pancreatic Adenocarcinoma

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Genetic: protein expression analysis; Procedure: therapeutic conventional surgery; Genetic: proteomic profiling; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Other: diagnostic laboratory biomarker analysis; Drug: gemcitabine hydrochloride; Drug: oxaliplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065-0009
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Gemcitabine And Oxaliplatin; A Phase II Study of Neoadjuvant Gemcitabine And Oxaliplatin In Patients With Potentially Resectable Previously Untreated Pancreatic Adenocarcinoma

Genetic: protein expression analysis; Procedure: therapeutic conventional surgery; Genetic: proteomic profiling; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Other: diagnostic laboratory biomarker analysis; Drug: gemcitabine hydrochloride; 1,000 mg/m2 IV over 100 minutes on day 1 every 14 days for 4 cycles; Drug: oxaliplatin; 80 mg/m2 IV over 2 hours on day 1 every 14 days for 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival at 18 Months	Percentage of participants that were alive or survived at 18 months after randomization	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	2 years
Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy		Baseline and 2 years
Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy	Percentage change in specific tumor marker (Carcinoembryonic antigen, CEA) levels in response to neoadjuvant therapy	Baseline and 2 years
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	Baseline and 2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Peter J. Allen, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: September 27, 2007
• First Submitted That Met QC Criteria: September 27, 2007
• First Posted (Estimate): September 28, 2007

Study Record Updates

• Last Update Posted (Actual): March 16, 2017
• Last Update Submitted That Met QC Criteria: February 7, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: adenocarcinoma of the pancreas; stage III pancreatic cancer; stage IIB pancreatic cancer; stage IA pancreatic cancer; stage IB pancreatic cancer; stage IIA pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Oxaliplatin
• Other Study ID Numbers: 07-113; MSKCC-07113