Clinical trial NCT00045500: UCN-01 and Prednisone in Treating Patients With Solid Tumors or Lymphoma
Official title: A Phase I Trial Of UCN-01 And Prednisone In Patients With Refractory Solid Tumors And Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
intraocular lymphoma
primary central nervous system non-Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult T-cell leukemia/lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent mantle cell lymphoma
unspecified adult solid tumor, protocol specific
recurrent adult Burkitt lymphoma
recurrent grade 3 follicular lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Bethesda
country: United States
facility: NCI - Center for Cancer Research
state: Maryland
city: Frederick
country: United States
facility: Frederick Cancer Research and Development Center
state: Maryland
Study officials:
affiliation: National Cancer Institute - Frederick
name: Giovanni Melillo, MD
role: STUDY_CHAIR
References: