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UCN-01 and Gemcitabine in Treating Patients With Unresectable or Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT00039403
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 23, 2013
Sponsor:
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Pancreas Recurrent Pancreatic Cancer Stage II Pancreatic Cancer Stage III Pancreatic Cancer Stage IV Pancreatic Cancer Drug: 7-hydroxystaurosporine Drug: gemcitabine hydrochloride Other: pharmacological study Other: laboratory biomarker analysis Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the safety and toxicity profile of UCN-01 when given in combination with gemcitabine to patients with unresectable or metastatic adenocarcinoma of the pancreas.

II. To characterize the pharmacokinetic profiles of gemcitabine and UCN-01 when given in combination and to correlate various measurements of UCN-01 with intracellular concentrations.

III. To determine recommended doses of UCN-01 and gemcitabine in combination to be used in a planned subsequent phase II trial.

SECONDARY OBJECTIVES:

I. To record the frequency, extent, and duration of any tumor responses. II. To correlate serum alpha-1 acid glycoprotein (AGP) levels with UCN-01 pharmacokinetics and toxicity.

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma
Study Start Date : April 2002
Primary Completion Date : May 2006

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Treatment (UCN-01, gemcitabine hydrochloride)

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.

Drug: 7-hydroxystaurosporine
Given IV
Other Name: UCN-01
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies


Outcome Measures

Primary Outcome Measures :
  1. Incidence of toxicity [ Time Frame: Up to 4 years ]
  2. Pharmacokinetic profiles [ Time Frame: Weeks 1-6 for UCN-01 and weeks 1 and 4 for intracellular gemcitabine ]
  3. Recommended phase II doses [ Time Frame: 3 weeks ]

Secondary Outcome Measures :
  1. Frequency, extent, and duration of any tumor responses [ Time Frame: Up to 4 years ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    • At least 20 mm by conventional techniques
    • 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
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 3 months
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count greater than 100,000/mm^3
  • Bilirubin no greater than 1.5 mg/dL
  • ALT and AST no greater than 2.5 times upper limit of normal
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • 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
  • No symptomatic pulmonary dysfunction
  • 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
  • No concurrent over-the-counter biologics
  • No concurrent growth factors during the first study course
  • 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
  • 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
  • At least 4 weeks since prior major surgery
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00039403


Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Linus Ho M.D. Anderson Cancer Center
More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00039403     History of Changes
Other Study ID Numbers: NCI-2012-02468
DM01-553
U01CA062461 ( U.S. NIH Grant/Contract )
CDR0000069380 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: January 23, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Pancreatic Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
7-hydroxystaurosporine
Staurosporine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors