Malignant Pleural EffusionPhase 1NCT00052338
Bortezomib Plus Gemcitabine and Carboplatin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer
A Phase 1 study testing gemcitabine hydrochloride, carboplatin and bortezomib in people with Malignant Pleural Effusion and Recurrent Non-small Cell Lung Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and bortezomib may kill more tumor cells Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Effusion, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer
- What is being tested?
- gemcitabine hydrochloride, carboplatin and bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2002to May 2004
- Phase
- Phase 1
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
Who may be able to join
- Histologically or cytologically confirmed non-small cell lung cancer
- Selected stage IIIB (malignant pleural effusion) or stage IV disease
- Recurrent disease after first-line therapy allowed
- Patients who received prior platinum-based chemotherapy must have no disease progression during or within 3 months after completion of therapy
- Patients who are enrolled at the maximum tolerated dose must have chemotherapy-naïve disease
- Evaluable disease
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- Asymptomatic brain metastases allowed if treated with surgical resection or radiotherapy, neurologically stable, and off steroids for at least 4 weeks
- Performance status - Karnofsky 60-100%
- More than 3 months
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 mg/dL
- AST no greater than 2.5 times upper limit of normal
- Creatinine normal
- Creatinine clearance at least 50 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No peripheral neuropathy grade 2 or greater
- No prior allergic reactions to compounds of similar chemical or biological composition to bortezomib or other agents used in this study
- No concurrent ongoing or active infection
- No other concurrent uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- No concurrent routine filgrastim (G-CSF)
- See Disease Characteristics
- No more than 1 prior chemotherapy regimen
- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
- No prior gemcitabine
- See Disease Characteristics
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy and recovered
- See Disease Characteristics
- More than 30 days since prior investigational drugs
- No prior bortezomib
- No concurrent anticonvulsant therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational or commercial agents or therapies with intent to treat malignancy
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study Of PS-341 In Combination With Gemcitabine And Carbloplatin In Selected Stage IIIB Or IV Non-Small Cell Lung Cancer
Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and bortezomib may kill more tumor cells
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the safety and feasibility of combining bortezomib with gemcitabine and carboplatin in patients with advanced or recurrent non-small cell lung cancer.
II. Determine the maximum tolerated dose of bortezomib administered in combination with gemcitabine and carboplatin in these patients.
III. Correlate results from laboratory studies on patient tissue and serum specimens with potential predictors of response in patients treated with this regimen.
IV. Determine, preliminarily, the response of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib.
Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30 minutes on day 1, followed 1 hour later by bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with a clinical or radiographic response may continue receiving bortezomib beyond 6 courses.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 10 additional patients with chemotherapy-naive disease receive treatment as above with the MTD of bortezomib.
Patients are followed for survival.
- Conditions
- Malignant Pleural Effusion, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- Being tested
- gemcitabine hydrochloride, carboplatin, bortezomib, laboratory biomarker analysis
- Medical subject headings
- Pleural Effusion, Malignant, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
carboplatinDrug
Also called Carboplat, CBDCA, JM-8, Paraplat
Given IV
bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (gemcitabine hydrochloride, carboplatin, bortezomib) | Experimental | Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30 minutes on day 1, followed 1 hour later by bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with a clinical or radiographic response may continue receiving bortezomib beyond 6 courses. Receives: Drug: gemcitabine hydrochloride; Drug: carboplatin; Drug: bortezomib; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicities at each dose level, graded using the CTC version 2.0
Summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, (by NCI Common Toxicity Criteria and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and course.
Measured: 18 weeks
Secondary outcomes (3)
Response rate, assessed by standard RECIST criteria
Summarized by exact binomial confidence intervals.
Measured: Up to 2 years
Survival
Summarized with Kaplan-Meier plots.
Measured: From registration to time of death due to any cause, assessed up to 2 years
Time to failure
Summarized with Kaplan-Meier plots.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startSep 2002
- Primary completionMay 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Pleural EffusionStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Angela Davies, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00052338
- Sponsor's protocol ID
- NCI-2012-02503
- Other IDs
- PHI-40, N01CM17101, CDR0000258189
- Status last verified
- Jan 2013
- First submitted
- 24 Jan 2003
- Last updated
- 23 Jan 2013
- Results posted
- No