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

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00047242

Purpose

RATIONALE: 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 chemotherapy may kill more tumor cells.

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

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

MedlinePlus related topics: Cancer

Drug Information available for: Irinotecan Irinotecan hydrochloride UCN 01

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	The Pharmacokinetic and Safety Profile of UCN-01 in Combination With Irinotecan in Solid Tumors (Primarily Lung, Ovarian and GI Cancers)

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

Estimated Enrollment:	30
Study Start Date:	August 2002

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose and recommended phase II dose of UCN-01 and irinotecan in patients with advanced solid tumors, primarily lung, ovarian, and gastrointestinal tumors.
Determine the acute and chronic toxicity profile of this regimen in these patients.
Determine the pharmacokinetics of this regimen in these patients.
Determine, preliminarily, the anti-tumor effect of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive UCN-01 IV over 3 hours on day 1 and irinotecan IV over 90 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of UCN-01 and irinotecan 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. At least 6 patients are treated at the recommended phase II dose.

Patients are followed at 1 month.

PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued for this study within 7-15 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative therapy does not exist or is no longer effective
- Gastrointestinal, lung, and ovarian malignancies are given priority
No brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

More than 3 months

Hematopoietic

WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin normal
AST/ALT no greater than 2.5 times upper limit of normal (ULN)

Renal

Creatinine normal OR
Creatinine clearance at least 60 mL/min

Cardiovascular

No symptomatic coronary artery disease
No symptomatic cardiac dysfunction
No symptoms suggestive of coronary artery disease
LVEF at least 50%

Pulmonary

No symptomatic pulmonary dysfunction
FEV_1 greater than 75% of predicted
DLCO greater than 75% of predicted

Other

Amylase no greater than 2 times ULN
No other concurrent uncontrolled illness
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
No diabetes mellitus or random glucose more than 200 mg/dL
No prior allergic reaction attributed to compounds of similar biological or chemical composition to UCN-01 or irinotecan (including rash and systemic allergic reaction causing hypotension and respiratory distress)
No chronic diarrhea (more than 5 stools/day)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception for 14 days before, during, and for at least 30 days after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Prior UCN-01 and irinotecan allowed

Endocrine therapy

Not specified

Radiotherapy

At least 4 weeks since prior radiotherapy and recovered
No prior mediastinal radiation

Surgery

Not specified

Other

At least 14 days since prior warfarin
No concurrent warfarin unless required for maintaining patency of existing, permanent IV catheters
No concurrent commercial or other investigational anticancer agents or therapies
No concurrent combination antiretroviral therapy for HIV-positive patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047242

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Ross C. Donehower, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

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

Publications of Results:

Jimeno A, Rudek MA, Purcell T, Laheru DA, Messersmith WA, Dancey J, Carducci MA, Baker SD, Hidalgo M, Donehower RC. Phase I and pharmacokinetic study of UCN-01 in combination with irinotecan in patients with solid tumors. Cancer Chemother Pharmacol. 2008 Mar;61(3):423-33. Epub 2007 Apr 12.

Study ID Numbers:	CDR0000257566, JHOC-J0173, NCI-5528
Study First Received:	October 3, 2002
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00047242
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Staurosporine
Irinotecan
7-hydroxystaurosporine
Camptothecin

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

Antineoplastic Agents, Phytogenic
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009