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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00039403
First received: June 6, 2002
Last updated: January 22, 2013
Last verified: January 2013

June 6, 2002
January 22, 2013
April 2002
May 2006   (final data collection date for primary outcome measure)
  • Incidence of toxicity [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic profiles [ Time Frame: Weeks 1-6 for UCN-01 and weeks 1 and 4 for intracellular gemcitabine ] [ Designated as safety issue: No ]
  • Recommended phase II doses [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00039403 on ClinicalTrials.gov Archive Site
Frequency, extent, and duration of any tumor responses [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
UCN-01 and Gemcitabine in Treating Patients With Unresectable or Metastatic Pancreatic Cancer
A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma

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

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adenocarcinoma of the Pancreas
  • Recurrent Pancreatic Cancer
  • Stage II Pancreatic Cancer
  • Stage III Pancreatic Cancer
  • Stage IV Pancreatic Cancer
  • 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
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.

Interventions:
  • Drug: 7-hydroxystaurosporine
  • Drug: gemcitabine hydrochloride
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
Not Provided
May 2006   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00039403
NCI-2012-02468, DM01-553, U01CA062461, CDR0000069380
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Linus Ho M.D. Anderson Cancer Center
National Cancer Institute (NCI)
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP