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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00012194
First received: March 3, 2001
Last updated: July 8, 2013
Last verified: July 2013
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Study of UCN-01 (NSC 638850) Plus Cisplatin in Advanced Malignant Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Graded using the NCI CTCAE.

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


Secondary Outcome Measures:
  • Objective tumor response [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Summarized at each dose level, and the number and percent responding combined across dose levels.

  • Overall survival [ Time Frame: From registration to time of death due to any cause, assessed up to 7 years ] [ Designated as safety issue: No ]
    Summarized with Kaplan-Meier plots.

  • 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 ] [ Designated as safety issue: No ]
    Summarized with Kaplan-Meier plots.

  • Duration of response [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Summarized with Kaplan-Meier plots.


Enrollment: 30
Study Start Date: March 2001
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

OBJECTIVES:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00012194

Locations
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Investigators
Principal Investigator: Raymond Perez Dartmouth-Hitchcock Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00012194     History of Changes
Obsolete Identifiers: NCT00227396
Other Study ID Numbers: NCI-2012-03129, DMS 9934, DMS-9934, NCI-2331
Study First Received: March 3, 2001
Last Updated: July 8, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
7-hydroxystaurosporine
Cisplatin
Staurosporine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014