UCN-01 and Cisplatin in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsor:	Dartmouth-Hitchcock Medical Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:	NCT00012194

Purpose

RATIONALE: 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.

PURPOSE: Phase I trial to study the effectiveness of combining UCN-01 with cisplatin in treating patients who have advanced solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: 7-hydroxystaurosporine Drug: cisplatin	Phase I

Study Type:	Interventional
Study Design:	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:

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin UCN 01

U.S. FDA Resources

Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:

Maximum tolerated dose (MTD). [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
To establish the maximum tolerated dose (MTD) of cisplatin in combination with UCN-01 in patients with advanced malignancies.

Secondary Outcome Measures:

Pharmacokinetics [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
To determine the pharmacokinetics of UCN-01 and cisplatin.
Toxicity assessment. [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
To assess the toxicity of UCN-01 plus cisplatin in advanced malignancies at each dose level studied.
Preliminary efficacy observation [ Time Frame: Cycle 1-2 (to day 56) ] [ Designated as safety issue: No ]
To observe the potential antitumor activity of UCN-01 plus cisplatin in advanced malignancies at each dose level studied.
Molecular correlative studies. [ Time Frame: Cycles 1-2 (up to day 56) ] [ Designated as safety issue: No ]
To perform laboratory correlative studies to investigate intermediate molecular markers of the activity of UCN-01 and cisplatin at the cellular level (geminin immunohistochemistry, AKT Thr 308 phosphorylation), and determinants of UCN-01 pharmacokinetics (salivary and plasma alpha-1-acid-glycoprotein (AAG)).

Enrollment:	13
Study Start Date:	March 2001
Study Completion Date:	January 2007
Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Intervention Details:

Intravenous dose titration.

Other Names:

UCN-01
NSC 638850

Intravenous, 1 hour infusion; dose titration.

Other Names:

Platinol
DDP
cisplatinum
cis-diamminedichloridoplatinum(II) (CDDP)
CAS 15663-27-1
NSC 119875

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of cisplatin when administered with UCN-01 in patients with advanced solid tumors.
Determine the toxicity and potential antitumor activity of this regimen in these patients.
Determine the pharmacokinetics of this regimen in these patients.

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.

PROJECTED ACCRUAL: A total of 9-30 patients will be accrued for this study within 12-18 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed advanced or metastatic solid tumor that is not amenable to standard therapy
No brain metastases

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

More than 3 months

Hematopoietic:

WBC at least 4,000/mm^3
Absolute neutrophil count at least 2,000/mm^3
Platelet count at least 150,000/mm^3

Hepatic:

Bilirubin normal
SGOT no greater than 2.5 times upper limit of normal

Renal:

Creatinine normal
Creatinine clearance at least 60 mL/min

Cardiovascular:

No coronary artery disease
No New York Heart Association class III or IV heart disease

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study
Must have central indwelling venous catheter
No peripheral neuropathy greater than grade 1
No prior allergic reaction to diuretics or antiemetics (e.g., 5-HT3 antagonists) to be administered during study
No clinically significant hearing loss
No uncontrolled concurrent illness that would preclude study therapy
No medical, social, or psychological factor that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No more than 2 prior chemotherapy regimens
At least 4 weeks since prior chemotherapy (at least 6 weeks for mitomycin or nitrosoureas) and recovered
Prior cumulative dose of cisplatin no greater than 250 mg/m^2

Endocrine therapy:

Not specified

Radiotherapy:

At least 4 weeks since prior radiotherapy and recovered
No prior radiotherapy to the mediastinum
No concurrent radiotherapy

Surgery:

Recovered from prior surgery

Other:

At least 30 days since prior investigational drugs
No other concurrent investigational drugs
No other concurrent anti-cancer agents

Contacts and Locations

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

Locations

United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002

Sponsors and Collaborators

Dartmouth-Hitchcock Medical Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Raymond P. Perez, MD

Norris Cotton Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Perez RP, Lewis LD, Beelen AP, Olszanski AJ, Johnston N, Rhodes CH, Beaulieu B, Ernstoff MS, Eastman A. Modulation of Cell Cycle Progression in Human Tumors: A Pharmacokinetic and Tumor Molecular Pharmacodynamic Study of Cisplatin Plus the Chk1 Inhibitor UCN-01 (NSC 638850). Clin Cancer Res. 2006 Dec 1;12(23):7079-85.

Responsible Party:	Raymond Perez, M.D./Principal Investigator, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:	NCT00012194 History of Changes
Obsolete Identifiers:	NCT00227396
Other Study ID Numbers:	CDR0000068492, P30CA023108, DMS-9934, NCI-2331
Study First Received:	March 3, 2001
Last Updated:	November 19, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:

unspecified adult solid tumor, protocol specific

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 February 12, 2012