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UCN-01 and Carboplatin in Treating Patients With Advanced 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.
 
ClinicalTrials.gov Identifier: NCT00036777
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : July 1, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE May 13, 2002
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date July 1, 2013
Study Start Date  ICMJE March 2002
Actual Primary Completion Date October 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2013)
Maximum tolerated dose of UCN-01 when combined with carboplatin determined by dose-limiting toxicities graded according to NCI Common Toxicity Criteria (CTC) [ Time Frame: 21 days ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2013)
  • Response rate [ Time Frame: Up to 3 years ]
    Reported with 95% confidence intervals.
  • Survival [ Time Frame: From the date of first treatment until death or last follow up, assessed up to 3 years ]
    Estimated utilizing Kaplan-Meier analysis.
  • Pharmacokinetics parameters of UCN-01 [ Time Frame: Prior to and at 0.5, 1, 2, and 3 hours after the start of the infusion and at 2, 4, 8, 24, 48 hours, and 7, and 21 days after the end of the infusion ]
    Will be determined using model independent and compartmental modeling methods. Will include, but not be limited too; the maximum plasma concentration (Cmax), area under the concentration versus time curve (AUC), terminal elimination half-life (t1/2), clearance (Cl), and volume of distribution (Vd).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE UCN-01 and Carboplatin in Treating Patients With Advanced Solid Tumors
Official Title  ICMJE A Phase 1 Study of UCN-01 in Combination With Carboplatin in Advanced Solid Tumors
Brief Summary Phase I trial to study the effectiveness of combining UCN-01 with carboplatin in treating patients who have advanced solid tumors. UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining UCN-01 with carboplatin may kill more tumor cells.
Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose, dose limiting toxicity and other toxicities of UCN-01 when combined with carboplatin.

II. Preliminarily evaluate the antitumor effect of the combination of carboplatin and UCN-01.

III. Determine the pharmacokinetics of UCN-01 and carboplatin.

OUTLINE: This is a dose-escalation study.

Patients receive carboplatin IV over 1 hour followed by UCN-01 IV over 3 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carboplatin and UCN-01 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unspecified Adult Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: carboplatin
    Given IV
    Other Names:
    • Carboplat
    • CBDCA
    • JM-8
    • Paraplat
    • Paraplatin
  • Drug: 7-hydroxystaurosporine
    Given IV
    Other Name: UCN-01
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Study Arms  ICMJE Experimental: Treatment (carboplatin, 7-hydroxystaurosporine)

Patients receive carboplatin IV over 1 hour followed by UCN-01 IV over 3 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carboplatin and UCN-01 until the 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.

Interventions:
  • Drug: carboplatin
  • Drug: 7-hydroxystaurosporine
  • Other: pharmacological study
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 31, 2013)
30
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date October 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • At least 4 weeks since prior chemotherapy or radiation therapy, 6 weeks if the last regimen included BCNU or mitomycin C; include site/total dose for prior radiation exposure as needed (e.g., no more than 3000 cGy to fields including substantial marrow)
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Leukocytes >= 3,000/microl
  • Absolute neutrophil count >= 1,500/microl
  • Platelets >= 100,000/microl
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) >= 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases are eligible providing the brain metastases are, in the opinion of the site investigator, asymptomatic or clinically stable after treatment with surgery and/or radiation therapy; patients should not require steroids or antiseizure medications and should have fully recovered from all therapy; at least two weeks should elapse between completion of any treatment for brain metastases (surgery, CNS irradiation) and commencement of protocol therapy
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to UCN-01 or other agents used in study
  • Because of cardiopulmonary toxicity seen in patients on other studies, patients with a symptomatic cardiac disease should be excluded; patients with a history of coronary artery disease or mediastinal radiation should undergo testing of ventricular function (cardiac echocardiogram, MUGA or equivalent) and are eligible if LVEF is >= 45%; if there is a history of prior pulmonary disease then pulmonary function tests should be performed and patients are eligible if FEV1 >= 1 liter
  • Because UCN-01 may cause hyperglycemia, patients with insulin dependent diabetes mellitus should be excluded
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this; breastfeeding should be discontinued if the mother is treated with UCN-01
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
  • Other drugs: Though not an exclusion criteria, every effort should be made to avoid drugs which may bind alpha-acid glycoprotein (AGP)
  • Patients with a history of severe allergic reactions to cisplatin or carboplatin
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00036777
Other Study ID Numbers  ICMJE NCI-2013-00042
UMGCC 0143
MSGCC-0143
NCI-5533
CDR0000069321
U01CA069854 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Martin Edelman University of Maryland Greenebaum Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date June 2013

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