Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of benzoylphenylurea in treating patients who have advanced solid tumors.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose of benzoylphenylurea in patients with advanced solid tumors. * Evaluate the acute and chronic toxicity profile of this regimen in these patients. * Evaluate the pharmacokinetics and metabolites of this regimen and any potential correlation with pharmacodynamic effects in these patients. * Determine the antitumor activity of this regimen in these patients. OUTLINE: This is a dose-escalation study. Patients receive oral benzoylphenylurea (BPU) once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of BPU 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 a dose-limiting toxicity. Once the MTD is determined, 12 additional patients are accrued and treated with BPU as above to confirm the MTD. Patients are followed for 30 days. PROJECTED ACCRUAL: Approximately 18-24 patients will be accrued for this study.
Interventions
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed malignancy * Metastatic or unresectable * No effective standard curative or palliative measures exist * No known CNS or brain metastasis PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * ECOG 0-1 Life expectancy: * Not specified Hematopoietic: * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin normal * SGOT/SGPT normal Renal: * Creatinine normal * Creatinine clearance at least 60 mL/min Cardiovascular: * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * No uncontrolled ventricular arrhythmia * No myocardial infarction within the past 3 months * No superior vena cava syndrome Neurologic: * No grade 1 or greater peripheral neuropathy * No uncontrolled major seizure disorder * No spinal cord compression Other: * No active serious infection requiring IV antibiotics * No concurrent uncontrolled illness * No concurrent unstable or serious medical condition * No chronic diarrhea or malabsorption * No history of allergic reactions to compounds similar in chemical or biological composition to benzoylphenylurea * No psychiatric illness or social situation that would preclude study compliance * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * No concurrent immunotherapy * No concurrent growth factors during first 2 courses of study * Concurrent epoetin alfa allowed Chemotherapy: * At least 28 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * No other concurrent chemotherapy Endocrine therapy: * No concurrent hormonal therapy Radiotherapy: * At least 28 days since prior large-field radiotherapy * Prior palliative radiotherapy for painful bone metastases allowed * No concurrent radiotherapy, including palliative or whole-brain radiotherapy for CNS disease Surgery: * At least 28 days since prior major surgery Other: * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational or commercial agents or therapies for the malignancy * No other concurrent investigational agents * Concurrent bisphosphonates allowed if bone metastases are not only site of measurable or evaluable disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Maximum Tolerated Dose of BPU | 4 weeks (1 course of treatment for each subject) | Toxicity was assessed weekly during the first 2 cycles, and monthly thereafter, using the National Cancer Institute Common Toxicity Criteria (NCI CTCv2). Dose limiting toxicity (DLT) was defined as dose delays \>2 weeks, grade 4 haematologic toxicity (except grade 4 neutropenia lasting \<5 days), or grade 3 nonhaematologic toxicity. The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Patients With Adverse Events | every 4 weeks |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of BPU | 8 weeks |
| Test for Antitumor Activity in Blood and Tissue | baseline |
Countries
United States
Participant flow
Recruitment details
Nineteen patients were enrolled between August 2001 and July 2004 at Johns Hopkins.
Pre-assignment details
Patients were excluded if they had known brain metastases, active infections, chronic diarrhoea, malabsorption, peripheral neuropathy \>grade 1 (NCI CTC v2), pregnancy, HIV infection, or serious concurrent medical conditions.
Participants by arm
| Arm | Count |
|---|---|
| Benzoylphenylurea BPU, administered over a dose range of 5-320 mg | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Benzoylphenylurea |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 1 / 19 |
Outcome results
Primary
Determine Maximum Tolerated Dose of BPU
Toxicity was assessed weekly during the first 2 cycles, and monthly thereafter, using the National Cancer Institute Common Toxicity Criteria (NCI CTCv2). Dose limiting toxicity (DLT) was defined as dose delays \>2 weeks, grade 4 haematologic toxicity (except grade 4 neutropenia lasting \<5 days), or grade 3 nonhaematologic toxicity. The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity.
Time frame: 4 weeks (1 course of treatment for each subject)
Population: Participants that completed at least 1 cycle of BPU.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Benzoylphenylurea | Determine Maximum Tolerated Dose of BPU | 150 milligrams (mg) |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of BPU
Time frame: 8 weeks
Secondary
Number of Patients With Adverse Events
Time frame: every 4 weeks
Secondary
Test for Antitumor Activity in Blood and Tissue
Time frame: baseline