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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00536874
• Other study ID #: 07-113
• Secondary ID: MSKCC-07113
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 27, 2007
• Last updated: November 16, 2016
• Start date: October 2007
• Est. completion date: September 2017

Study information

• Verified date: November 2016
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 39
• Est. completion date: September 2017
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• 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.

Genetic:
• protein expression analysis

• proteomic profiling

Other:
• diagnostic laboratory biomarker analysis

Procedure:
• adjuvant therapy

• neoadjuvant therapy

• therapeutic conventional surgery

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival at 18 Months	Percentage of participants that were alive or survived at 18 months after randomization	18 months	No
Secondary	Overall Survival (Follow-Up Time)		From Baseline until 2 Years and Follow-Up, up to 120 months	No
Secondary	Specific Tumor Marker Response (CEA) to Neoadjuvant Therapy		Baseline and 2 years	No
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	2 years	No
Secondary	Specific Tumor Marker Response (Ca 19-9) to Neoadjuvant Therapy		Baseline and 2 years	No
Secondary	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	No
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	Baseline and 2 years	No