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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

Phase I Dose Escalation Study of UCN-01 (NSC 638850) Plus Cisplatin in Advanced Malignant Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00012194
• Other study ID #: NCI-2012-03129
• Secondary ID: DMS 9934DMS-9934
• Status: Terminated
• Phase: Phase 1
• First received: March 3, 2001
• Last updated: July 8, 2013
• Start date: March 2001

Study information

• Verified date: July 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00227396

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• 7-hydroxystaurosporine
Given IV
• cisplatin
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Graded using the NCI CTCAE.	4 weeks	Yes
Primary	Toxicity observed at each dose level, graded using the NCI CTCAE	Summarized in terms of type, severity, time of onset, duration, and reversibility or outcome.	Up to 7 years	Yes
Secondary	Objective tumor response	Summarized at each dose level, and the number and percent responding combined across dose levels.	Up to 7 years	No
Secondary	Overall survival	Summarized with Kaplan-Meier plots.	From registration to time of death due to any cause, assessed up to 7 years	No
Secondary	Time to treatment failure	Summarized with Kaplan-Meier plots.	From registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 7 years	No
Secondary	Duration of response	Summarized with Kaplan-Meier plots.	Up to 7 years	No