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UCN-01 and Gemcitabine in Treating Patients With Unresectable or Metastatic Pancreatic Cancer
This study has been completed.
First Received: June 6, 2002   Last Updated: July 23, 2008   History of Changes
Sponsors and Collaborators: M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00039403
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. UCN-01 may help gemcitabine kill more cancer cells by making tumor cells more sensitive to the drug.

PURPOSE: Phase I trial to study the effectiveness of combining UCN-01 with gemcitabine in treating patients who have unresectable or metastatic pancreatic cancer.


Condition Intervention Phase
Pancreatic Cancer
Drug: 7-hydroxystaurosporine
Drug: gemcitabine hydrochloride
Phase I

MedlinePlus related topics: Cancer Pancreatic Cancer
Drug Information available for: Gemcitabine UCN 01 Gemcitabine hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma

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

Study Start Date: May 2002
Detailed Description:

OBJECTIVES:

  • Determine the safety, toxicity profile, and maximum tolerated dose of UCN-01 and gemcitabine in patients with unresectable or metastatic adenocarcinoma of the pancreas.
  • Characterize the pharmacokinetic profile of this regimen in these patients.
  • Correlate various surrogate measurements of UCN-01 with intracellular concentrations in these patients.
  • Determine the recommended phase II dose of this regimen in these patients.
  • Determine the frequency, extent, and duration of any tumor responses in patients treated with this regimen.
  • Correlate serum alpha-1 acid glycoprotein levels in these patients with the pharmacokinetics and toxicity of UCN-01.

OUTLINE: This is a dose-escalation study.

Patients receive gemcitabine IV over 1-2 hours on days 1 and 8 followed by UCN-01 IV over 3 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Sequential dose escalation of UCN-01 is followed by sequential dose escalation of gemcitabine. Cohorts of 3-6 patients receive escalating doses of UCN-01 and then gemcitabine until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 patients are treated at the recommended phase II dose.

PROJECTED ACCRUAL: Approximately 6-30 patients will be accrued for this study within 2-15 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the pancreas
  • Unidimensionally measurable disease

    • At least 20 mm by conventional techniques OR
    • At least 10 mm by spiral CT scan
    • Tumor lesions in a previously irradiated area are not considered measurable
  • No known brain metastases

    • Patients with signs or symptoms of CNS metastasis at any time during screening must have a negative CT scan or MRI of the brain

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy:

  • More than 3 months

Hematopoietic:

  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count greater than 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • ALT and AST no greater than 2.5 times upper limit of normal

Renal:

  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • No prior coronary artery disease
  • No symptomatic cardiac dysfunction
  • No prior myocardial infarction
  • No active angina (even if controlled by medication)
  • No positive stress test
  • No uncontrolled arrhythmia
  • Left ventricular ejection fraction at least 45%
  • Patients with symptoms suggestive of coronary artery disease or arrhythmia must have no evidence of cardiac pathology

Pulmonary:

  • No symptomatic pulmonary dysfunction

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No prior allergic reactions attributed to compounds of similar chemical or biological composition to UCN-01 or other study agents
  • No insulin-dependent diabetes mellitus
  • No other concurrent uncontrolled illness
  • No ongoing or active infections
  • No concurrent psychiatric illness
  • No other active malignancy
  • No other solid tumor within the past 5 years except neoplasia in situ or nonmelanomatous skin cancer
  • No social situations that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent over-the-counter biologics
  • No concurrent growth factors during the first study course

Chemotherapy:

  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No more than 2 prior chemotherapy regimens (e.g., gemcitabine and/or experimental agents) alone or in combination with radiotherapy as neoadjuvant or adjuvant therapy for resectable, unresectable, or metastatic disease

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics
  • See Chemotherapy
  • At least 6 weeks since prior radiotherapy and recovered
  • Prior radiotherapy directed only at the primary tumor bed allowed
  • No prior radiotherapy to the mediastinum, pelvis, lower spine, or more than 20% of bone marrow

Surgery:

  • See Disease Characteristics
  • At least 4 weeks since prior major surgery

Other:

  • At least 4 weeks since prior investigational agents
  • Concurrent enrollment in non-therapy trials (e.g., quality of life) allowed
  • No concurrent herbal remedies
  • No concurrent treatment for another active malignancy
  • No concurrent warfarin for anticoagulation
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational or commercial anticancer agents or therapies
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00039403

Locations
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Linus Ho, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000069380, MDA-DM-01553, NCI-5510
Study First Received: June 6, 2002
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00039403     History of Changes
Health Authority: United States: Federal Government

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

Study placed in the following topic categories:
Antimetabolites
Digestive System Neoplasms
Immunologic Factors
Pancreatic Neoplasms
Endocrine System Diseases
7-hydroxystaurosporine
Protein Kinase Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pancrelipase
Recurrence
Carcinoma
Digestive System Diseases
Radiation-Sensitizing Agents
Staurosporine
Gastrointestinal Neoplasms
Pancreatic Diseases
Endocrinopathy
Adenocarcinoma
Gemcitabine
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Protein Kinase Inhibitors
Neoplasms by Site
Therapeutic Uses
Staurosporine
Gemcitabine
Endocrine Gland Neoplasms
Digestive System Neoplasms
Endocrine System Diseases
Enzyme Inhibitors
7-hydroxystaurosporine
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Pancreatic Diseases

ClinicalTrials.gov processed this record on May 07, 2009