Clinical trial NCT00016354: Benzoylphenylurea in Treating Patients With Advanced Solid Tumors
Official title: Phase I Study of Continuous Weekly Dosing of Dimethyl Benzoylphenylurea (BPU) in Patients With Solid Tumors Not Responding to Conventional Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Determine Maximum Tolerated Dose of BPU
timeFrame: 4 weeks (1 course of treatment for each subject)
Secondary outcomes:
measure: Number of Patients With Adverse Events
timeFrame: every 4 weeks
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of BPU
timeFrame: 8 weeks
measure: Test for Antitumor Activity in Blood and Tissue
timeFrame: baseline
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Antonio C. Wolff, MD
role: STUDY_CHAIR
References:
citation: Messersmith WA, Rudek MA, Baker SD, Zhao M, Collins C, Colevas AD, Donehower RC, Carducci MA, Wolff AC. Phase I study of continuous weekly dosing of dimethylamino benzoylphenylurea (BPU) in patients with solid tumours. Eur J Cancer. 2007 Jan;43(1):78-86. doi: 10.1016/j.ejca.2006.09.006. Epub 2006 Nov 3.
citation: Messersmith WA, Baker SD, Donehower RC, et al.: Phase I study of continuous weekly dosing of dimethyl benzoylphenylurea (BPU) in patients with solid tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-815, 2003.