Chemoradiation in Locally Advanced Pancreatic Cancer - Full Text View

Sponsor:	Masonic Cancer Center, University of Minnesota
Information provided by (Responsible Party):	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00262951

Purpose

RATIONALE: Drugs used in chemotherapy, such as fluorouracil and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Interferon alfa may interfere with the growth of tumor cells. Giving combination chemotherapy and radiation therapy together with interferon alfa before surgery may shrink the tumor so it can 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 combination chemotherapy and radiation therapy together with interferon alfa works in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Condition	Intervention	Phase
Pancreatic Cancer	Biological: recombinant interferon alfa Drug: cisplatin Drug: fluorouracil Radiation: radiation therapy Procedure: Resection of tumor	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Pilot Study of Multi-Agent Neo-Adjuvant Chemoradiation in Patients With Locally Advanced Pancreatic Adenocarcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Fluorouracil Cisplatin Interferon alfa-2a Interferon alfa-n1 Interferons

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:

Number of Patients in Whom Tumor Was Resectable [ Time Frame: Up to 5 Years or Until Disease Progression ] [ Designated as safety issue: No ]
Tumor response is measured in terms of resectability, as measured by CT scan at 2 weeks after completion of each course. A CT scan of the chest abdomen and pelvis will be performed in order to evaluate for the presence of metastatic disease. If no metastatic disease, emphasis will be paid to the local tumor. Evaluation of the growth/regression of the tumor will be made as it relates to resectability. If potential for resection then surgery will be recommended. This protocol will be followed after each cycle.

Secondary Outcome Measures:

Overall Survival [ Time Frame: Up to 5 Years or Date of Death, Whichever Occurred First ] [ Designated as safety issue: No ]
In all patients, measured from the date of the patient's registration in this study, until the date of the patient's death or date last known alive (if observation was censored).

Enrollment:	23
Study Start Date:	January 2005
Study Completion Date:	August 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Pancreatic Adenocarcinoma Patients Pancreatic Adenocarcinoma Patients treated with chemotherapy regimen and radiation (and or surgery).	Biological: recombinant interferon alfa administered subcutaneously (SQ)at a dose of 3 million units Day 1,3, and 5 each week in Cycle 1 Other Names: IFN alpha IFN-alpha-2b Drug: cisplatin administered at a dose of 30 mg/m2 intravenously (IV) day 1 each week in Cycle 1 Other Names: cisplatinum cis-diamminedichloroplatinum(II) (CDDP) Drug: fluorouracil administered at a dose of 175 mg/m^2/day continuous infusion (CI) for 38 days in Cycle 1 and then 500 mg/m^2 intravenously (IV) each week for 6 weeks followed by a 2 week rest (1 cycle = 8 weeks)in Cycle 2 and 3 Other Name: 5-FU Radiation: radiation therapy 5040 cGy total, in 28 fractions, at 180 cGy/fraction daily, Monday -Friday, for 5½ weeks (days 1-5, 8-12, 15-19, 22-26, 29-33, 36-38). Procedure: Resection of tumor After Cycle 1 treatment (if resectable)- In the absence of metastatic disease, special emphasis will be paid to the local tumor. Evaluation of the growth/regression of the tumor will be made as it relates to resectability. Surgical exploration will start with a diagnostic laparoscopy. If no evidence of carcinomatosis, liver metastases or other evidence of metastatic disease is encountered, then a laparotomy will be performed. In the absence of clear technical unresectability, a radical pancreaticoduodenectomy, distal or total pancreatectomy (and resection of any involved structures) will be performed as mandated by tumor anatomy.

Arms

Assigned Interventions

Experimental: Pancreatic Adenocarcinoma Patients

Pancreatic Adenocarcinoma Patients treated with chemotherapy regimen and radiation (and or surgery).

Biological: recombinant interferon alfa

administered subcutaneously (SQ)at a dose of 3 million units Day 1,3, and 5 each week in Cycle 1

Other Names:

IFN alpha
IFN-alpha-2b

Drug: cisplatin

administered at a dose of 30 mg/m2 intravenously (IV) day 1 each week in Cycle 1

Other Names:

cisplatinum
cis-diamminedichloroplatinum(II) (CDDP)

Drug: fluorouracil

administered at a dose of 175 mg/m^2/day continuous infusion (CI) for 38 days in Cycle 1 and then 500 mg/m^2 intravenously (IV) each week for 6 weeks followed by a 2 week rest (1 cycle = 8 weeks)in Cycle 2 and 3

Other Name: 5-FU

Radiation: radiation therapy

5040 cGy total, in 28 fractions, at 180 cGy/fraction daily, Monday -Friday, for 5½ weeks (days 1-5, 8-12, 15-19, 22-26, 29-33, 36-38).

Procedure: Resection of tumor

After Cycle 1 treatment (if resectable)- In the absence of metastatic disease, special emphasis will be paid to the local tumor. Evaluation of the growth/regression of the tumor will be made as it relates to resectability. Surgical exploration will start with a diagnostic laparoscopy. If no evidence of carcinomatosis, liver metastases or other evidence of metastatic disease is encountered, then a laparotomy will be performed. In the absence of clear technical unresectability, a radical pancreaticoduodenectomy, distal or total pancreatectomy (and resection of any involved structures) will be performed as mandated by tumor anatomy.

Detailed Description:

OBJECTIVES:

Primary

Determine the effect of neoadjuvant chemoradiotherapy and interferon alfa on converting patients with locally advanced unresectable adenocarcinoma of the pancreas to resectability.

Secondary

Determine the rate and severity of early and late toxic effects of these regimens in these patients.
Improve surgical morbidity profile and overall survival of patients who undergo surgical resection.
Determine overall and progression-free survival of patients treated with this regimen.

OUTLINE: This is an pilot, single center study.

Part 1 (neoadjuvant therapy): Patients receive fluorouracil IV continuously over 24 hours on days 1-38; cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36; and interferon alfa subcutaneously on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, and 38. Patients also undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38. Patients then undergo restaging. Patients with resectable disease undergo surgery, and 4-10 weeks later, proceed to part 2. Patients with unresectable disease proceed directly to part 2, 4 weeks after completion of neoadjuvant therapy.
Part 2 (chemotherapy): Patients receive fluorouracil IV on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 56 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with unresectable disease undergo restaging after each course of fluorouracil. If the tumor subsequently becomes resectable, patients then undergo surgery.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

Eligibility

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

Criteria

Inclusion Criteria:

Patient must have newly diagnosed computated tomography (CT) and endoscopic ultrasound(EUS) stage Tx-4, N0-1, M0 adenocarcinoma of pancreas according to the American Joint Committee on Cancer (AJCC) staging system. The following cell types will NOT be eligible: adenosquamous carcinoma, ampullary carcinoma, carcinoid tumor, cystadenocarcinoma, cystadenoma, distal common bile duct carcinoma, duodenal carcinoma, or islet cell carcinoma
Treatment must begin within 60 days of diagnosis
Must have locally advanced inoperable pancreatic cancer with no metastatic spread as determined by a baseline diagnostic CT scan of the chest, endoscopic ultrasound and CT scan with intravenous (IV) contrast (or MRI) of abdomen/pelvis, within 30 days prior to registration.
No prior systemic chemotherapy or radiation therapy for pancreatic cancer
Documented Eastern Cooperative Oncology Group (ECOG/Zubrod) performance status 0-1 within 14 days prior to registration
Adequate hematologic, renal and hepatic function as defined by the following laboratory values (completed within 14 days prior to registration)
- white blood cell (WBC) > 3,000 mm3
- absolute neutrophil count (ANC) > 1,500 mm3
- platelet count ≥ 100,000 mm3
- hemoglobin > 9.5 g/dl
- serum creatinine < 1.5 times institutional upper limit of normal (ULN)
- total bilirubin ≤ 3 mg/dl
- AST (SGOT) < 4.0 times institutional ULN
- ALT (SGPT) < 4.0 times institutional ULN
- alkaline phosphatase < 2.0 times institutional ULN
Age ≥ 18 years
Life expectancy ≥ 12 weeks
Patient (male or female) of reproductive potential are required to use a medically acceptable contraception during treatment and for 3 months after the last dose of chemotherapy.
Not pregnant or breastfeeding since the drugs used in this study are Pregnancy Category D: Clear evidence of risk in pregnancy. A negative pregnancy test is required within 7 days of registration if pre- or perimenopausal (i.e., last menstrual period within one year of registration)
If patient has a previous diagnosis of cancer, all of the following criteria must be met and documented in the patient's medical record:
- Patient has undergone potentially curative therapy for all prior malignancies.
- No evidence of prior malignancies for at least 5 years (except for successfully treated cervical carcinoma in situ, carcinoma in situ of the breast, or nonmelanoma skin cancer.
- No evidence of recurrence of any prior malignancy.
Patient who is receiving chronic immunotherapy (e.g. prednisone or methotrexate) for collagen vascular disease or other chronic immunologic abnormality are not eligible.
Not requiring one or more of the contraindicated medications
Patient must be able to understand the potential risks and benefits associated with this study. Patient able to give informed consent and would likely to comply with the study parameters.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262951

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Study Chair:

Edward W. Greeno, MD

Masonic Cancer Center, University of Minnesota

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:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00262951 History of Changes
Other Study ID Numbers:	2004LS060, 0410M64346
Study First Received:	December 6, 2005
Results First Received:	November 14, 2011
Last Updated:	January 3, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:

stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
adenocarcinoma of the pancreas

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
Interferon-alpha
Interferon Alfa-2a
Interferons

Fluorouracil
Cisplatin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Radiation-Sensitizing Agents
Antimetabolites

ClinicalTrials.gov processed this record on February 09, 2012