UCN-01 and Prednisone in Treating Patients With Solid Tumors or Lymphoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00045500

Collaborator

(none)

Locations

Study Details

Study Description

Brief Summary

RATIONALE: UCN-01 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining UCN-01 with prednisone may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining UCN-01 with prednisone in treating patients who have refractory solid tumors or lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Drug: 7-hydroxystaurosporine Drug: prednisone	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of UCN-01 in combination with prednisone in patients with refractory solid tumors or lymphomas.
Determine the toxic effects of this regimen in these patients.
Assess the pharmacokinetics of this regimen in these patients.
Assess any tumor response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of UCN-01.

Patients receive oral prednisone daily on days 1-5 and UCN-01 IV over 36-72 hours on days 3-5. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of UCN-01 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 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 every 3-12 months for 5 years.

PROJECTED ACCRUAL: Approximately 24 patients will be accrued for this study within 18 months.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I Trial Of UCN-01 And Prednisone In Patients With Refractory Solid Tumors And Lymphomas

Study Start Date :

Jun 1, 2002

Actual Primary Completion Date :

Jan 1, 2010

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed solid tumor or lymphoma
Progressive disease after standard therapy
No other therapy is likely to improve survival
Prostate cancer patients must have progressed through hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists and withdrawal of testosterone receptor antagonists
Patients must continue on GnRH agonist during study (if orchiectomy has not been performed) and have castrate testosterone levels
Brain metastases allowed if treated and the patient has been stable off anti-seizure medication or steroids for > 6 months
No local complications from disease requiring urgent therapy (i.e., hydronephrosis, spinal cord compression, or severe pain requiring improved pain management)

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

At least 3 months

Hematopoietic

Absolute neutrophil count greater than 1,000/mm^3
Platelet count greater than 100,000/mm^3
12-hour fasting glucose no greater than 110 mg/dL OR
12-hour fasting glucose no greater than 140 mg/dL with hemoglobin A1C no greater than 6.5 mg/dL

Hepatic

PT/PTT no greater than 1.5 times upper limit of normal (ULN)
Bilirubin no greater than 1.5 times ULN (unless Gilbert's syndrome present)
AST/ALT no greater than 2.5 times ULN

Renal

Creatinine clearance greater than 60 mL/min OR
Creatinine no greater than 1.5 mg/dL

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris

Pulmonary

No interstitial lung disease within the past year
No requirement for oxygen therapy for hypoxia in the past 6 months

Gastrointestinal

No diagnosis of duodenal or gastric ulcer
No severe gastritis within the past 6 months

Other

HIV negative
No prior allergic reactions to other indolocarbazoles
No diabetes or hyperglycemia within the past year that required a diabetic diet, oral hypoglycemics, or insulin
No other uncontrolled illness
No active infection
No seizure disorder
No psychiatric illness that would preclude study compliance
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 2 months after study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No prior UCN-01

Endocrine therapy

See Disease Characteristics
No other concurrent oral or IV steroids

Radiotherapy

At least 4 weeks since prior radiotherapy and recovered

Surgery

See Disease Characteristics
At least 21 days since prior major surgery

Other

See Disease Characteristics
At least 4 weeks since prior investigational agents
No other concurrent anticancer therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
2	NCI - Center for Cancer Research	Bethesda	Maryland	United States	20892
3	Frederick Cancer Research and Development Center	Frederick	Maryland	United States	21702-1201