- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00388089
Bortezomib and Topotecan in Treating Patients With Advanced Solid Tumors
Phase I Study of Weekly Bortezomib (VELCADE, PS-341) and Weekly Topotecan (HYCAMTIN) in Solid Tumor Patients With an Emphasis on Small Cell Lung Cancer (SCLC)
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.
Study Overview
Status
Detailed Description
OBJECTIVES:
Primary
- Evaluate the safety and feasibility of bortezomib and topotecan hydrochloride in patients with advanced solid tumors.
Secondary
- Determine the maximum tolerated dose (MTD) of bortezomib and topotecan hydrochloride in these patients.
- Determine, preliminarily, the efficacy of this regimen in these patients.
- Perform laboratory correlative studies on tumor tissue and blood samples from these patients to investigate potential predictors of response.
- Obtain fresh tumor tissue for correlative studies from a subset of patients with small cell lung cancer treated at the MTD.
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Sacramento, California, United States, 95817
- University of California Davis Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety
Time Frame: Monitored on an ongoing basis during the study
|
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.
|
Monitored on an ongoing basis during the study
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity
Time Frame: On Day 8 and at beginning of subsequent cycles
|
Toxicity will be evaluated based on the standard NCI CTC grading criteria version 3.0.
|
On Day 8 and at beginning of subsequent cycles
|
Response rate
Time Frame: At baseline and every 2 courses during treatment
|
As assessed by RECIST criteria
|
At baseline and every 2 courses during treatment
|
Best response
Time Frame: From start of treatment until disease progression/recurrence
|
Best response is determined from the sequence of objective status.
|
From start of treatment until disease progression/recurrence
|
Survival
Time Frame: From registration to time of death due to any cause
|
Patients will be followed for 30 days after removal from study treatment or until all treatment-related toxicities resolve to < grade 1.
|
From registration to time of death due to any cause
|
Progression-free survival
Time Frame: From registration to the first observation of disease progression or death due to any cause
|
If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up.
|
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
Time Frame: From pre-treatment to post-treatment
|
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
|
From pre-treatment to post-treatment
|
NF-kB and BCL-2 family activity as assessed by immunohistochemistry
Time Frame: From pre-treatment to post-treatment
|
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
|
From pre-treatment to post-treatment
|
Loss of p27 as assessed by immunohistochemistry
Time Frame: From pre-treatment to post-treatment
|
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
|
From pre-treatment to post-treatment
|
Hypoxia-induced plasma proteins as measured by enzyme-linked immunosorbent assay (ELISA)
Time Frame: From pre-treatment to post-treatment
|
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
|
From pre-treatment to post-treatment
|
Shed tumor DNA in plasma
Time Frame: From pre-treatment to post-treatment
|
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
|
From pre-treatment to post-treatment
|
Biological activity of bortezomib as measured by flow cytometry
Time Frame: From pre-treatment to post-treatment
|
The aim of these molecular correlates is to examine the relationship between these studies and the clinical response to treatment.
|
From pre-treatment to post-treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Angela Davies, MD, University of California, Davis
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CDR0000505990
- P30CA093373 (U.S. NIH Grant/Contract)
- UCDCC-157 (Other Identifier: University of California, Davis - Cancer Center)
- 200412738 (Other Identifier: University of California, Davis - IRB)
- GSK-8531 (Other Grant/Funding Number: GlaxoSmithKline)
- MILLENNIUM-X05131 (Other Grant/Funding Number: Millennium Pharmaceuticals)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lung Cancer
-
M.D. Anderson Cancer CenterRecruitingStage III Lung Cancer AJCC v8 | Lung Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage... and other conditionsUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)RecruitingStage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingCaregiver | Stage III Lung Cancer AJCC v7 | Stage I Lung Cancer AJCC v7 | Stage II Lung Cancer AJCC v7 | Stage IB Lung Cancer AJCC v7 | Stage IA Lung Cancer AJCC v7 | Stage IIA Lung Cancer AJCC v7 | Stage IIB Lung Cancer AJCC v7 | Stage IIIA Lung Cancer AJCC v7 | Stage IIIB Lung Cancer AJCC v7United States
-
Dana-Farber Cancer InstituteMedWaves, IncNot yet recruitingLung Cancer | Lung Cancer Stage I | Lung Cancer Stage II | Stage I Lung Cancer | Stage I - II Primary Lung Cancer | Stage II Lung CancerUnited States
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI); Genentech, Inc.RecruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Lung Non-Small Cell Carcinoma | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung... and other conditionsUnited States
-
Emory UniversityNational Cancer Institute (NCI)TerminatedLung Non-Small Cell Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
University of California, San FranciscoMerck Sharp & Dohme LLCWithdrawnLung Non-Small Cell Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Metastatic Lung Carcinoma | Stage IV Lung Cancer AJCC v8 | Head and Neck Carcinoma | Lung Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung... and other conditionsUnited States
Clinical Trials on bortezomib
-
The First Affiliated Hospital of Soochow UniversityUnknownMultiple Myeloma Proved by Laboratory TestsChina
-
Baylor College of MedicineMillennium Pharmaceuticals, Inc.CompletedProstate NeoplasmsUnited States
-
NCIC Clinical Trials GroupCompleted
-
University Hospital, Clermont-FerrandLaboratoires TakedaUnknownMultiple Myeloma | Adult | Bortezomib RegimenFrance
-
Janssen-Cilag International NVCompletedMultiple MyelomaTurkey, Greece, Czech Republic, Austria, Germany, Sweden, United Kingdom, Denmark
-
University Health Network, TorontoNational Cancer Institute (NCI)CompletedBladder Cancer | Transitional Cell Cancer of the Renal Pelvis and UreterUnited States, Canada
-
Southwest Oncology GroupNational Cancer Institute (NCI)Completed
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)CompletedLymphoma | Myelodysplastic Syndromes | Leukemia | Multiple Myeloma and Plasma Cell NeoplasmUnited States
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)Completed
-
NYU Langone HealthNational Cancer Institute (NCI)CompletedLymphoma | Small Intestine Cancer | Unspecified Adult Solid Tumor, Protocol SpecificUnited States