Bortezomib and Topotecan Hydrochloride in Treating Patients With Advanced Solid Tumors
- Conditions
- Unspecified Adult Solid Tumor, Protocol Specific
- Interventions
- Other: immunohistochemistry staining methodOther: pharmacological study
- Registration Number
- NCT00541359
- Lead Sponsor
- City of Hope Medical Center
- Brief Summary
RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with topotecan hydrochloride may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of topotecan hydrochloride when given together with bortezomib in treating patients with advanced solid tumors.
- Detailed Description
PRIMARY OBJECTIVES:
I. To assess the safety and feasibility of combining PS-341 with topotecan in patients with advanced solid tumor malignancies.
II. To define the maximum tolerated dose (MTD) of topotecan when administered in combination with a fixed dose of PS-341 and to described the toxicities at each dose studied.
III. To evaluate the pharmacokinetics of topotecan when given in combination with PS-341 at MTD.
SECONDARY OBJECTIVES:
I. To perform laboratory correlative studies on patients tissue investigating potential predictors of response.
OUTLINE:
PART I (completed as of 09/06/06; all patients enrolled in study after 09/06/06 are enrolled in part II): Patients receive escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8 followed 6 hours later by bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.
PART II: Patients receive bortezomib IV on days 1, 4, 8, and 11 followed 6 hours later by escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.
In both parts of the study, patients who achieve a response may receive additional courses of treatment.
After completion of study treatment, patients are followed periodically.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm I topotecan hydrochloride PART I (completed as of 09/06/06; all patients enrolled in study after 09/06/06 are enrolled in part II): Patients receive escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8 followed 6 hours later by bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. PART II: Patients receive bortezomib IV on days 1, 4, 8, and 11 followed 6 hours later by escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. In both parts of the study, patients who achieve a response may receive additional courses of treatment. Arm I immunohistochemistry staining method PART I (completed as of 09/06/06; all patients enrolled in study after 09/06/06 are enrolled in part II): Patients receive escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8 followed 6 hours later by bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. PART II: Patients receive bortezomib IV on days 1, 4, 8, and 11 followed 6 hours later by escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. In both parts of the study, patients who achieve a response may receive additional courses of treatment. Arm I pharmacological study PART I (completed as of 09/06/06; all patients enrolled in study after 09/06/06 are enrolled in part II): Patients receive escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8 followed 6 hours later by bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. PART II: Patients receive bortezomib IV on days 1, 4, 8, and 11 followed 6 hours later by escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. In both parts of the study, patients who achieve a response may receive additional courses of treatment. Arm I bortezomib PART I (completed as of 09/06/06; all patients enrolled in study after 09/06/06 are enrolled in part II): Patients receive escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8 followed 6 hours later by bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. PART II: Patients receive bortezomib IV on days 1, 4, 8, and 11 followed 6 hours later by escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. In both parts of the study, patients who achieve a response may receive additional courses of treatment.
- Primary Outcome Measures
Name Time Method Toxicity as assessed by NCI CTCAE v3.0 21 days after the end of treatment
- Secondary Outcome Measures
Name Time Method Overall survival 1 year from the end of treatment Progression-free survival 1 year from the end of treatment Time to progression 1 year from the end of treatment Levels of NF-kB activation At baseline and completion of treatment
Trial Locations
- Locations (2)
City of Hope Medical Center
🇺🇸Duarte, California, United States
City of Hope Medical Group Inc
🇺🇸Pasadena, California, United States