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7-hydroxystaurosporine and Cisplatin in Treating Patients With Advanced Malignant Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00012194
Recruitment Status : Terminated
First Posted : January 27, 2003
Last Update Posted : July 9, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
Phase I trial to study the effectiveness of combining UCN-01 with cisplatin in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth and may help cisplatin kill more cancer cells by making tumor cells more sensitive to the drug.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: 7-hydroxystaurosporine Drug: cisplatin Other: laboratory biomarker analysis Phase 1

Detailed Description:


I. To establish the maximum tolerated dose (MTD) of cisplatin in combination with UCN-01 in patients with advanced malignancies.

II. To assess the toxicity and observe the potential antitumor activity of UCN-01 plus cisplatin in advanced malignancies at each dose level studies.

III. To determine the pharmacokinetics of UCN-01 and cisplatin on this treatment schedule.

IV. To perform laboratory correlative studies to investigate intermediate molecular markers of the activity of UCN-01 and cisplatin at the cellular level.

OUTLINE: This is a dose-escalation study of cisplatin.

Patients receive cisplatin IV over 1 hour on day 1 and UCN-01 IV continuously over 36-72 hours on day 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of cisplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 2-3 months for at least 1 year.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Study of UCN-01 (NSC 638850) Plus Cisplatin in Advanced Malignant Solid Tumors
Study Start Date : March 2001
Actual Primary Completion Date : January 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

Arm Intervention/treatment
Experimental: Treatment (7-hydroxystaurosporine, cisplatin)
Patients receive cisplatin IV over 1 hour on day 1 and UCN-01 IV continuously over 36-72 hours on day 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: 7-hydroxystaurosporine
Given IV
Other Name: UCN-01

Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. MTD of cisplatin defined as the highest dose level in which six patients have been evaluated for toxicity with no more than one patient experiencing DLT attributable to the study drugs [ Time Frame: 4 weeks ]
    Graded using the NCI CTCAE.

  2. Toxicity observed at each dose level, graded using the NCI CTCAE [ Time Frame: Up to 7 years ]
    Summarized in terms of type, severity, time of onset, duration, and reversibility or outcome.

Secondary Outcome Measures :
  1. Objective tumor response [ Time Frame: Up to 7 years ]
    Summarized at each dose level, and the number and percent responding combined across dose levels.

  2. Overall survival [ Time Frame: From registration to time of death due to any cause, assessed up to 7 years ]
    Summarized with Kaplan-Meier plots.

  3. Time to treatment failure [ Time Frame: From registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 7 years ]
    Summarized with Kaplan-Meier plots.

  4. Duration of response [ Time Frame: Up to 7 years ]
    Summarized with Kaplan-Meier plots.

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Advanced or metastatic, histologcally/cytologically confirmed malignant solid tumor, not expected to clinically benefit from standard therapy
  • Life expectancy greater than 3 months
  • Previous chemotherapy and/or radiotherapy must have been completed at least four weeks (six weeks for prior treatment with mitomycin or nitrosoureas) and patients should have recovered from all toxicities of that therapy before treatment under this protocol
  • All patients must have recovered from any surgical procedure
  • Serum creatinine must be within the institutional limits of normal and an estimated creatinine clearance of >= 60 ml/min
  • Normal bilirubin is required
  • SGOT/AST must be less than or equal to 2.5 times the upper limit of institutional normal
  • WBC >= 4000/mm^3
  • Absolute neutrophil count >= 2000/mm^3
  • Platelet count >= 150,000/mm^3
  • Patients must have a Karnofsky Performance Status of 60% or greater
  • Subjects who are fertile must use a medically acceptable contraceptive throughout the treatment period and for three months following cessation of treatment; subjects must be made aware, before entering this trial, of the risk in becoming pregnant or in fathering children
  • A signed informed consent (approved by the IRB) must be obtained prior to trial entry
  • Tumor site accessible for both pre-treatment and post-treatment biopsy is preferred during dose-finding, and is required for patients entering the expanded cohort at the MTD
  • All patients require a central indwelling venous catheter prior to treatment under this protocol

Exclusion Criteria:

  • Peripheral neuropathy > grade I
  • Any prior mediastinal radiotherapy
  • Any history of coronary artery disease
  • Class III or IV congestive heart failure according to the New York Heart Classification
  • History of allergic reactions to appropriate diuretics or antiemetics (e.g., 5-HT3 antagonists) to be administered in conjunction with protocol directed chemotherapy
  • Brain metastasis
  • Uncontrolled intercurrent illness that would preclude tolerance and completion of the protocol treatment, including vigorous hydration prior and subsequent to cisplatin therapy
  • Lactating or pregnant women are excluded to avoid potential harm to the unborn child or infant; documentation of a negative, serum beta-HCG pregnancy test must be available for pre-menopausal women with intact reproductive organs and for women less than two years after menopause
  • Receipt of any investigational drug within 30 days before beginning treatment with study drug
  • Medical, social, or psychological factors that would prevent the patient from completing the treatment protocol
  • Patients with clinically significant hearing loss

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 identifier (NCT number): NCT00012194

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United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Raymond Perez Dartmouth-Hitchcock Medical Center

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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00012194     History of Changes
Obsolete Identifiers: NCT00227396
Other Study ID Numbers: NCI-2012-03129
DMS 9934
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: July 9, 2013
Last Verified: July 2013
Additional relevant MeSH terms:
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Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action