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Cisplatin, Metronomic Low-Dose Interferon Alfa, Gemcitabine, and Fever-Range Whole-Body Hyperthermia in Treating Patients With Inoperable or Metastatic Pancreatic Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), December 2008
First Received: May 14, 2004   Last Updated: April 14, 2009   History of Changes
Sponsored by: The University of Texas Health Science Center, Houston
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00082862
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Biological: recombinant interferon alfa
Drug: cisplatin
Drug: gemcitabine hydrochloride
Procedure: hyperthermia treatment
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor response [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Survival [ Designated as safety issue: No ]
  • Changes in quality of life [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Conversion of inoperable tumors to operable [ Designated as safety issue: No ]
  • Changes in cellular and cytokine immune function [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: July 2002
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00082862

Locations
United States, Texas
University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77225
Contact: Joan M.C. Bull, MD     713-500-6820     joan.m.bull@uth.tmc.edu    
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Joan M.C. Bull, MD The University of Texas Health Science Center, Houston
  More Information

Additional Information:
Publications:
Responsible Party: University of Texas Health Science Center at Houston ( Joan M.C. Bull )
Study ID Numbers: CDR0000360863, UTHSC-MS-02117
Study First Received: May 14, 2004
Last Updated: April 14, 2009
ClinicalTrials.gov Identifier: NCT00082862     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage II pancreatic cancer
stage III pancreatic cancer
recurrent pancreatic cancer
stage IV pancreatic cancer

Study placed in the following topic categories:
Antimetabolites
Interferon-alpha
Anti-Infective Agents
Interferon Type I, Recombinant
Digestive System Neoplasms
Immunologic Factors
Pancreatic Neoplasms
Interferons
Endocrine System Diseases
Immunosuppressive Agents
Angiogenesis Inhibitors
Antiviral Agents
Recurrence
Fever
Digestive System Diseases
Radiation-Sensitizing Agents
Cisplatin
Gastrointestinal Neoplasms
Pancreatic Diseases
Endocrinopathy
Gemcitabine
Interferon Alfa-2a
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Interferon Type I, Recombinant
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Neoplasms by Site
Cisplatin
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors
Gemcitabine
Endocrine Gland Neoplasms
Interferon-alpha
Digestive System Neoplasms
Growth Substances
Interferons
Endocrine System Diseases
Enzyme Inhibitors
Immunosuppressive Agents
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Pancreatic Diseases

ClinicalTrials.gov processed this record on September 03, 2009