Clinical trial NCT00059826: Adjuvant Chemoradiotherapy and Interferon Alfa in Treating Patients With Resected Pancreatic Cancer
Official title: A Phase II Study of Interferon-Based Adjuvant Chemoradiation in Patients With Resected Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
adenocarcinoma of the pancreas
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-07
Enrollment: 89
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 fluorouracil and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of tumor cells. Radiation therapy uses high-energy radiation from x-rays and other sources to kill tumor cells. Combining chemotherapy with interferon alfa and giving them with radiation therapy after surgery may kill any remaining tumor cells.

PURPOSE: Phase II trial to study the effectiveness of adjuvant chemoradiotherapy and interferon alfa in treating patients who have resected stage I, stage II, or stage III pancreatic cancer.

Detailed description: OBJECTIVES:

* Determine the disease-free and overall survival of patients with resected pancreatic adenocarcinoma treated with adjuvant chemoradiotherapy comprising fluorouracil, cisplatin, and interferon alfa.
* Determine the rate and severity of acute and late toxic effects in patients treated with this regimen.
* Determine the local-regional disease control and distant disease control in patients treated with this regimen.

OUTLINE: This is a multicenter study.

* Chemoradiotherapy (CRT): Patients receive fluorouracil IV continuously 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.
* Post-CRT chemotherapy: Beginning 4-6 weeks after the completion of CRT, patients receive fluorouracil IV continuously on days 1-42. Treatment repeats every 56 days for a total of two courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

1. Patient must be \> 18 years of age.
2. Patient must have a documented ECOG/Zubrod performance status of 0 or 1, within 7 days prior to registration.
3. Patient must have pathological stage T1-3, N0-1, M0 adenocarcinoma of the head of the pancreas according to the American Joint Committee on Cancer (AJCC) staging system.

   * NOTE: The pathology report must be submitted to ACOSOG on the Pathology Report Shuttle CRF.
4. Patient must have undergone a potentially curative gross total resection by pancreaticoduodenectomy (includes R0 \[no residual tumor\] or R1 \[microscopic residual tumor\]) within 56 days prior to beginning treatment. NOTE: The operative report must be submitted to ACOSOG on the Operative Report Shuttle CRF.
5. Patient must have stable or increasing weight in the 14 days prior to the start of treatment, otherwise supplemental nutrition (e.g. feeding jejunostomy, PEG, TPN) must be initiated prior to the start of treatment.6. Patient must have adequate bone marrow, hepatic and renal function, within 7 days prior to registration:

   * WBC \> 3,000 mm\^3
   * ANC \> 1,500 mm\^3
   * hemoglobin \> 9.5 mg/dl
   * platelet count \> 100,000 mm\^3
   * total bilirubin \< 3 mg/dl
   * AST (SGOT) \< 2.0 times institutional upper limit of normal (ULN)
   * ALT (SGPT) \< 2.0 times institutional ULN
   * alkaline phosphatase \< 2.0 times institutional ULN
   * serum creatinine \< 1.5 times institutional ULN

7. Patient must have a baseline diagnostic CT scan of the chest and CT scan with IV contrast (or MRI) of abdomen/pelvis, within 30 days prior to registration, to exclude metastatic disease.

8. If female of childbearing potential, patient must have a negative urine or serum pregnancy test, within 7 days prior to registration. NOTE: Postmenopausal women must have been amenorrheic for at least 12 consecutive months to be considered not of childbearing potential.

9. Patient (male or female) of reproductive potential must agree to use medically acceptable contraception during the study. NOTE: Medically acceptable contraceptives include: (1) surgical sterilization, (2) approved hormonal contraceptives (such as birth control pills, Depo-Provera, or Lupron Depot), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD).

10. Patient, or the patient's legally acceptable representative, must sign and date an informed consent PRIOR to registration and the performance of any study related procedures.

11. Patient, or the patient's legally acceptable representative, must provide written authorization to allow the use and disclosure of their protected health information.

- NOTE: This may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration.

12. If patient is a cancer survivor, all of the following criteria must be met and documented in the patient's medical record:

1. Patient has undergone potentially curative therapy for all prior malignancies.
2. No evidence of prior malignancies for at least 5 years (except for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, or nonmelanoma skin cancer).
3. No evidence of recurrence of any prior malignancy.

Exclusion Criteria:

1. Patient has pancreaticoduodenectomy histopathology of adenosquamous carcinoma, ampullary carcinoma, carcinoid tumor, cystadenocarcinoma, cystadenoma, distal common bile duct carcinoma, duodenal carcinoma, or islet cell carcinoma.
2. Patient is pregnant or lactating.
3. Patient has recurrent pancreatic cancer.
4. Patient has received prior systemic chemotherapy or radiotherapy for pancreatic cancer.
5. Patient has received external beam photon (x-ray) therapy to the chest, abdomen or pelvis.
6. Patient has received any biologic/ immunologic therapies.
7. Patient has received chronic immunotherapy (e.g. prednisone or methotrexate) for collagen vascular disease or other chronic immunologic abnormality.
8. Patient has a preexisting psychiatric condition, especially depression, or a history of severe psychiatric disorders.

Primary outcomes:
measure: Overall survival at 18 months
timeFrame: at 18 months
Secondary outcomes:
measure: Toxicity
timeFrame: at 18 months
measure: Disease-free survival
timeFrame: at 18 months
measure: Local-regional disease control
timeFrame: at 18 months
measure: Distant disease control
timeFrame: at 18 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Louisville
country: United States
facility: James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: Fairview University Medical Center - University Campus
state: Minnesota
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Presbyterian Hospital of Dallas
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
Study officials:
affiliation: Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center
name: Vincent J. Picozzi, MD
role: STUDY_CHAIR
References:
citation: Picozzi VJ, Abrams RA, Decker PA, Traverso W, O'Reilly EM, Greeno E, Martin RC, Wilfong LS, Rothenberg ML, Posner MC, Pisters PW; American College of Surgeons Oncology Group. Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation: ACOSOG Trial Z05031. Ann Oncol. 2011 Feb;22(2):348-54. doi: 10.1093/annonc/mdq384. Epub 2010 Jul 29.
citation: Picozzi VJ, Abrams RA, Traverso LW, et al.: ACOSOG Z05031: initial report of a multicenter, phase II trial of a novel chemoradiation protocol using cisplatin, 5-FU, and alpha- interferon as adjuvant therapy for resected pancreas cancer. [Abstract] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-125, 2008.
citation: Picozzi VJ, Abrams RA, Traverso LW, et al.: ACOSOG Z05031: report on a multicenter, phase II trial for adjuvant therapy of resected pancreatic cancer using cisplatin, 5- FU, and alpha-interferon. [Abstract] J Clin Oncol 26 (Suppl 15): A-4505, 2008.