Cisplatin, Metronomic Low-Dose Interferon Alfa, Gemcitabine, And Fever-Range Whole-Body Hyperthermia In Treating Patients With Inoperable Or Metastatic Pancreatic Cancer

Study Overview

Cisplatin, Metronomic Low-Dose Interferon Alfa, Gemcitabine, and Fever-Range Whole-Body Hyperthermia in Treating Patients With Inoperable or Metastatic Pancreatic Cancer

RATIONALE: Drugs used in chemotherapy, such as cisplatin and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving low-dose interferon alfa on a metronomic (regularly timed) schedule may stop the growth of cancer by stopping blood flow to the tumor. Fever-range (above 101° F) whole-body hyperthermia kills tumor cells by heating them to several degrees above normal body temperature. Combining cisplatin, gemcitabine, and low-dose interferon alfa with fever-range whole-body hyperthermia may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cisplatin, gemcitabine, and metronomic low-dose interferon alfa together with fever-range whole-body hyperthermia works in treating patients with inoperable or metastatic pancreatic cancer.

OBJECTIVES: Primary * Determine tumor response in patients with inoperable or metastatic pancreatic cancer treated with cisplatin, metronomic low-dose interferon alfa, gemcitabine, and fever-range whole-body hyperthermia. * Determine the toxicity of this regimen in these patients. * Determine the survival of patients treated with this regimen. * Determine changes in quality of life in patients treated with this regimen. Secondary * Determine whether inoperable tumors convert to operable in patients treated with this regimen. * Determine changes in cellular and cytokine immune function in patients treated with this regimen. OUTLINE: Patients are stratified according to disease stage (metastatic vs inoperable). Patients receive cisplatin IV over 4-6 hours on day 1, interferon alfa subcutaneously once daily on days 1-28, and gemcitabine IV over 1 hour on days 3 and 10. Patients undergo fever-range whole-body hyperthermia (40°C over 6 hours) on day 3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and then before each treatment course. PROJECTED ACCRUAL: A total of 18-48 patients (9-24 per stratum) will be accrued for this study within 4 years.

Pancreatic Cancer

BIOLOGICAL: recombinant interferon alfa
DRUG: cisplatin
DRUG: gemcitabine hydrochloride
PROCEDURE: hyperthermia treatment

CDR0000360863
UTHSC-MS-02117

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2004-05-14	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2012-02-10
First Submitted that Met QC Criteria 2004-05-18	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2012-02-13
First Posted (ESTIMATED) 2004-05-19	Results First Posted N/A	Last Verified 2008-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
N/A

Interventional Model:
N/A

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
Tumor response
Toxicity
Survival
Changes in quality of life

Secondary Outcome Measures	Measure Description	Time Frame
Conversion of inoperable tumors to operable
Changes in cellular and cytokine immune function

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically confirmed pancreatic carcinoma

Inoperable or metastatic disease
Measurable lesion by physical examination, CT scan, or MRI

Carcinomatous hepatomegaly is considered measurable if a palpable liver edge clearly extends > 15 cm below the costal margin or xiphoid process
No known brain metastases by CT scan or MRI

18 and over

Karnofsky 70-100%

At least 12 weeks

Absolute granulocyte count ≥ 1,500/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Hemoglobin > 10.0 g/dL
Platelet count ≥ 90,000/mm^3
Bone marrow cellularity normal on bone marrow biopsy
No serious coagulopathy disorder

Bilirubin ≤ 2.5 mg/dL
SGPT and SGOT ≤ 2 times upper limit of normal
PT < 14 seconds
PTT < 35 seconds
INR < 1.5

Creatinine ≤ 1.8 mg/dL
Creatinine clearance ≥ 45 mL/min
Blood urea nitrogen ≤ 25 mg/dL

Adequate cardiovascular function as documented by the following:

History and physical examination
Stress exercise test (MUGA or echocardiogram) with resting blood pressure, heart rate, and LVEF that increase appropriately with exercise
LVEF ≥ 45%
No myocardial infarction within the past 6 months
No symptomatic coronary artery disease
No angina
No unstable blood pressure
No congestive heart failure
No significant arrhythmia
No conduction disturbance
No thromboembolic disease
No uncontrolled hypertension

Complete pulmonary function studies with the following arterial blood gas values:

FEV_1 ≥ 70% of predicted
Arterial PO_2 ≥ 60 mm Hg on room air
PCO_2 appropriate
pH appropriate
No massive (≥ 30%) lung disease
DLCO > 50% of predicted

No prior or concurrent seizures or other CNS disorders
No prior malignant hyperthermia after general anesthesia
No insulin-dependent diabetes mellitus
No significant emotional instability
No other medical problem that would preclude treatment with whole-body hyperthermia
HIV negative
Not pregnant or nursing

Prior biologic therapy allowed

No prior cisplatin or gemcitabine

No concurrent adrenal corticosteroids

More than 3 weeks since prior radiotherapy

More than 6 days since prior major thoracic or abdominal surgery
Prior surgical resection of tumor with subsequent recurrence allowed

No concurrent cardiac glycosides
No concurrent anti-angina or arrhythmia drugs
No concurrent thrombolytic agents
No concurrent anticoagulants
No concurrent aspirin

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Joan M.C. Bull, MD, The University of Texas Health Science Center, Houston

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Bull JM, Scott GL, Strebel FR, Nagle VL, Oliver D, Redwine M, Rowe RW, Ahn CW, Koch SM. Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and daily interferon-alpha: a description of a phase I-II protocol. Int J Hyperthermia. 2008 Dec;24(8):649-62. doi: 10.1080/02656730802104740.

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