Gemcitabine and Oxaliplatin in Treating Patients With Pancreatic Cancer That Can Be Removed By Surgery - Full Text View

Purpose

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.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: gemcitabine hydrochloride Drug: oxaliplatin Genetic: protein expression analysis Genetic: proteomic profiling Other: diagnostic laboratory biomarker analysis Procedure: adjuvant therapy Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of Neoadjuvant Gemcitabine and Oxaliplatin in Patients With Potentially Resectable Previously Untreated Pancreatic Adenocarcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Oxaliplatin Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

Overall survival at 18 months [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Patterns of recurrence (local vs distant) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Safety, toxicity, and feasibility of neoadjuvant therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Toxicity of adjuvant therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Feasibility of obtaining preoperative core tissue biopsies [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Exploratory analysis of pathologic correlates of response following neoadjuvant therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Feasibility of xenograft production from core tissues [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Specific tumor marker response (CEA, CA19-9) to neoadjuvant therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Prognostic accuracy of serum protein profiles [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	39
Study Start Date:	October 2007
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Gemcitabine And Oxaliplatin A Phase II Study of Neoadjuvant Gemcitabine And Oxaliplatin In Patients With Potentially Resectable Previously Untreated Pancreatic Adenocarcinoma	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. Genetic: protein expression analysis Genetic: proteomic profiling Other: diagnostic laboratory biomarker analysis Procedure: adjuvant therapy Procedure: neoadjuvant therapy Procedure: therapeutic conventional 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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00536874

Locations

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

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Eileen O'Reilly, MD	Memorial Sloan-Kettering Cancer Center
Principal Investigator:	Peter J. Allen, MD	Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00536874 History of Changes
Other Study ID Numbers:	07-113, MSKCC-07113
Study First Received:	September 27, 2007
Last Updated:	September 19, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

adenocarcinoma of the pancreas
stage IA pancreatic cancer
stage IB pancreatic cancer

stage IIA pancreatic cancer
stage IIB pancreatic cancer
stage III pancreatic cancer

Additional relevant MeSH terms:

Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Oxaliplatin

Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on May 19, 2013