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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Clinical Trial of a Timing/Schedule Optimized Combined-Modality Regimen: Cisplatin + Metronomic Low-Dose Interferon-α (IFN-α) Followed by Gemcitabine HCl (GEMZAR) in Combination With Mild, Fever-Range Whole-Body Hyperthermia (FR-WBH) in Patients With Advanced, Inoperable Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: recombinant interferon alfa
* Drug: cisplatin
* Drug: gemcitabine hydrochloride
* Procedure: hyperthermia treatment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: 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 PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy At least 12 weeks Hematopoietic 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 Hepatic Bilirubin ≤ 2.5 mg/dL SGPT and SGOT ≤ 2 times upper limit of normal PT < 14 seconds PTT < 35 seconds INR < 1.5 Renal Creatinine ≤ 1.8 mg/dL Creatinine clearance ≥ 45 mL/min Blood urea nitrogen ≤ 25 mg/dL Cardiovascular 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 Pulmonary 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 Other 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 CONCURRENT THERAPY: Biologic therapy Prior biologic therapy allowed Chemotherapy No prior cisplatin or gemcitabine Endocrine therapy No concurrent adrenal corticosteroids Radiotherapy More than 3 weeks since prior radiotherapy Surgery More than 6 days since prior major thoracic or abdominal surgery Prior surgical resection of tumor with subsequent recurrence allowed Other No concurrent cardiac glycosides No concurrent anti-angina or arrhythmia drugs No concurrent thrombolytic agents No concurrent anticoagulants No concurrent aspirin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: recombinant interferon alfa|nan|
|Drug: cisplatin|nan|
|Drug: gemcitabine hydrochloride|nan|
|Procedure: hyperthermia treatment|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response |  |  | 
| Toxicity |  |  | 
| Survival |  |  | 
| Changes in quality of life |  |  | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II pancreatic cancer, stage III pancreatic cancer, recurrent pancreatic cancer, stage IV pancreatic cancer