Bortezomib and Topotecan in Treating Patients With Advanced Solid Tumors

• Status: Completed
• Trial end date: 2008-06-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan, 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 may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib and topotecan in treating patients with advanced solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Davis
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bortezomib; Topotecan

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced solid tumor, meeting 1 of the following criteria:

• Disease progressed after ≥ 1 prior standard therapy regimen

• Treatment-naive with no standard therapy of curative intent available

• Not a candidate for standard therapy due to poor performance status

• Patients with small cell lung cancer are enrolled after the maximum tolerated dose has been determined

• Must have tumor accessible for biopsy

• Measurable disease by RECIST criteria or evaluable disease (e.g., pleural effusion, ascites, or bone metastasis)

• Disease in previously irradiated sites is considered measurable provided there is clear disease progression after radiotherapy

• Asymptomatic brain metastasis treated by prior surgical resection or radiotherapy allowed if both of the following criteria are met:

• Neurologically stable

• Off steroids and anticonvulsants for ≥ 4 weeks

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Life expectancy ≥ 3 months

• Absolute neutrophil count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine clearance ≥ 40 mL/min

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST and ALT ≤ 3.0 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No preexisting neuropathy ≥ grade 2 within the past 14 days

• No hypersensitivity to bortezomib, boron, or mannitol

• No myocardial infarction within the past 6 months

• No New York Heart Association class III or IV heart failure

• No uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia or active conduction system abnormalities

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Any number of prior chemotherapy regimens allowed

• At least 4 weeks since prior chemotherapy and recovered

• At least 2 weeks since prior radiotherapy and recovered

• No prior topotecan hydrochloride or bevacizumab

• At least 14 days since prior investigational drugs

• No concurrent anticonvulsants metabolized by the cytochrome P450 pathway