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AzTrials

Lung CancerPhase 1NCT00388089

Bortezomib and Topotecan in Treating Patients With Advanced Solid Tumors

A Phase 1 study testing bortezomib, topotecan hydrochloride and flow cytometry in people with Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by University of California, Davis at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bortezomib, topotecan hydrochloride and flow cytometry
How many people
24 participants
Where
1 siteUnited States
Study dates
Dec 2004to Jun 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California Davis Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
bortezomib, topotecan hydrochloride, flow cytometry, immunoenzyme technique, immunohistochemistry staining method
Keywords
unspecified adult solid tumor, protocol specific, extensive stage small cell lung cancer, recurrent small cell lung cancer
Medical subject headings
Lung Neoplasms, Small Cell Lung Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bortezomibDrug

    Also called PS-341, Velcade

    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

  • topotecan hydrochlorideDrug

    Also called Hycamtin

    Dose level A: 3 mg/m2; Dose level B: 3 mg/m2; Dose level C: 3 mg/m2; Dose level D: 4 mg/m2

  • flow cytometryOther

    No description

  • immunoenzyme techniqueOther

    No description

  • immunohistochemistry staining methodOther

    No description

  • laboratory biomarker analysisOther

    No description

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Monitored on an ongoing basis during the study

Secondary outcomes (11)

  1. Toxicity

    Toxicity will be evaluated based on the standard NCI CTC grading criteria version 3.0.

    Measured: On Day 8 and at beginning of subsequent cycles

  2. Response rate

    As assessed by RECIST criteria

    Measured: At baseline and every 2 courses during treatment

  3. Best response

    Best response is determined from the sequence of objective status.

    Measured: From start of treatment until disease progression/recurrence

  4. Survival

    Patients will be followed for 30 days after removal from study treatment or until all treatment-related toxicities resolve to < grade 1.

    Measured: From registration to time of death due to any cause

  5. Progression-free survival

    If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up.

    Measured: From registration to the first observation of disease progression or death due to any cause

  6. 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.

    Measured: From pre-treatment to post-treatment

  7. 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.

    Measured: From pre-treatment to post-treatment

  8. 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.

    Measured: From pre-treatment to post-treatment

  9. 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.

    Measured: From pre-treatment to post-treatment

  10. 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.

    Measured: From pre-treatment to post-treatment

  11. 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.

    Measured: From pre-treatment to post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2006 (estimated)
  2. Study startDec 2004
  3. Primary completionNov 2007
  4. Study completionJun 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00388089
Sponsor's protocol ID
CDR0000505990
Other IDs
P30CA093373, UCDCC-157, 200412738, GSK-8531, MILLENNIUM-X05131
Status last verified
Dec 2007
First submitted
12 Oct 2006
Last updated
29 Jun 2010
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bortezomib, topotecan hydrochloride and flow cytometry in people with Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by University of California, Davis at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety (time frame: Monitored on an ongoing basis during the study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00388089.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2010.

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