A Phase 1 interventional study of bortezomib and topotecan hydrochloride in Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, sponsored by University of California, Davis. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2010-06-29.
Sponsored by University of California, Davis · Phase 1, Interventional, and Treatment
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.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a dose-escalation study.
Patients receive topotecan hydrochloride IV over 30 minutes followed by bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may continue to receive bortezomib alone in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan hydrochloride and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Ten additional patients with small cell lung cancer are treated at the MTD. These patients undergo tumor biopsy at baseline and before the second course of therapy.
Tumor tissue is collected at baseline in all patients. Blood samples are collected at baseline, at the beginning of courses 2 and 3, and after completion of study treatment. Samples are examined for topoisomerase-1 levels by western blotting; BCL-2, BCL-xL, BAX, and p27 by immunohistochemistry; hypoxia-inducible factor-1, plasminogen-activator inhibitor 1, vascular endothelial growth factor, and osteopontin by immunoenzyme techniques; and NF-kB and p27 nuclear expression by flow cytometry.
After completion of study treatment, patients are followed for 30 days.
PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.
7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.
This study's enrollment of 24 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.
Browse Lung Neoplasms studies →University of California, Davis is the lead sponsor of 798 studies on the registry; 146 are open to participants now.
Of its 65 completed or terminated interventional studies of FDA-regulated products, 43 (66%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed advanced solid tumor, meeting 1 of the following criteria:
Patients with small cell lung cancer are enrolled after the maximum tolerated dose has been determined
Measurable disease by RECIST criteria or evaluable disease (e.g., pleural effusion, ascites, or bone metastasis)
Asymptomatic brain metastasis treated by prior surgical resection or radiotherapy allowed if both of the following criteria are met:
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Dose level A: 1 mg/m2; Dose level B: 1.3 mg/m2; Dose level C: 1.6 mg/m2; Dose level D: 1.6 mg/m2
Also known as: PS-341, Velcade
Dose level A: 3 mg/m2; Dose level B: 3 mg/m2; Dose level C: 3 mg/m2; Dose level D: 4 mg/m2
Also known as: Hycamtin
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Safety
If cumulative toxicities are seen in subsequent treatment cycles, a decision regarding modification or discontinuation of the study drug and/or patient enrollment will be made by the sponsor in conjunction with the investigator.
Time frame: Monitored on an ongoing basis during the study
Toxicity
Toxicity will be evaluated based on the standard NCI CTC grading criteria version 3.0.
Time frame: On Day 8 and at beginning of subsequent cycles
Response rate
As assessed by RECIST criteria
Time frame: At baseline and every 2 courses during treatment
Best response
Best response is determined from the sequence of objective status.
Time frame: From start of treatment until disease progression/recurrence
Survival
Patients will be followed for 30 days after removal from study treatment or until all treatment-related toxicities resolve to \< grade 1.
Time frame: From registration to time of death due to any cause
Progression-free survival
If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up.
Time frame: From registration to the first observation of disease progression or death due to any cause
Topoisomerase levels as assessed by western blot and tumor tissue biopsy
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
Time frame: From pre-treatment to post-treatment
NF-kB and BCL-2 family activity as assessed by immunohistochemistry
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
Time frame: From pre-treatment to post-treatment
Loss of p27 as assessed by immunohistochemistry
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
Time frame: From pre-treatment to post-treatment
Hypoxia-induced plasma proteins as measured by enzyme-linked immunosorbent assay (ELISA)
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
Time frame: From pre-treatment to post-treatment
Shed tumor DNA in plasma
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
Time frame: From pre-treatment to post-treatment
Biological activity of bortezomib as measured by flow cytometry
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
Time frame: From pre-treatment to post-treatment
This study is completed, as verified in Dec 2007. You cannot join it, but the record below documents what was studied.
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University of California, Davis