Non Small Cell Lung CancerPhase 2NCT01633645
Bortezomib in Combination With Gemcitabine and Cisplatin in Advanced or Metastatic Non-Small Cell Lung Cancer
A Phase 2 study testing Bortezomib, Gemcitabine and Cisplatin in people with Non Small Cell Lung Cancer and Metastatic, run by University Hospital of Crete at 5 sites in Greece.
Trial summary
The primary objective of this study is to establish the objective response rate (complete response + partial response) following treatment with VELCADE in combination with cisplatin plus gemcitabine in patients with locally advanced (Stage IIIb) or metastatic (stage IV non-small cell lung cancer (NSCLC) who have not… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Metastatic
- What is being tested?
- Bortezomib, Gemcitabine and Cisplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 5 sitesGreece
- Study dates
- Jun 2009to Apr 2013
- Phase
- Phase 2
- 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
Who may be able to join
- Men or women, 18 years of age or older.
- NSCLC histologically or cytologically confirmed.
- Locally advanced (Stage IIIB) or metastatic (Stage IV) NSCLC.
- No prior systemic anti-neoplastic therapy for Stage IIIB/IV NSCLC (one prior line is allowed if given as adjuvant or neo-adjuvant therapy).
- Measurable disease per RECIST criteria.
- ECOG performance status score of 0 - 1.
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- Life expectancy greater than 3 months.
- Female patients must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum or urine β-human chorionic gonadotropin (hCG) pregnancy test at screening.
- Patients (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to and able to comply with the protocol requirements and participate in the study before any study-related procedure not part of normal medical care is conducted.
- Patients (or their legally acceptable representatives) must have signed an informed consent for testing indicating, that they agree to participate in the correlative marker part of the study.
Who cannot join
- Peripheral neuropathy of Grade 2 or greater intensity, as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE Version 3.0).
- Previous treatment with VELCADE.
- Prior systemic anti-neoplastic therapies for Stage IIIB/IV NSCLC except if as neoadjuvant therapy for Stage IIIB.
- Any prior systemic anti-neoplastic therapy for NSCLC (i.e., prior chemotherapy, radiation therapy, prior monoclonal antibodies or any investigational drug or any major surgery) within 4 weeks before enrollment.
- Significant weight loss (documented < 10% body weight in the 6 weeks before enrollment).
- Inadequate organ function at the screening visit as defined by the following laboratory values:
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- Platelet count ≤ 100 x 109/L
- Hemoglobin ≤ 8.0 g/dL (80 g/L)
- Absolute neutrophil count (ANC) ≤ 1.5 x 109/L
- AST ≥ 3 times the upper limit of the normal range (upper normal limit) or > 5 times the upper normal limit for subjects with liver metastases
- ALT ≥ 3 times ULN or > 5 times the upper normal limit for subjects with liver metastases (Calculated creatinine clearance ≥ 45 mL/min, Total bilirubin ≥ 1.5 times Upper normal limit)
- Myocardial infarction within 6 months before randomization or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Central nervous system metastasis or brain metastases unless patients have been subjected to local radiation therapy and are clinically stable. Brain computed tomography or magnetic resonance imaging is required in symptomatic patients to rule out brain metastases but is not required in asymptomatic patients.
- Serious medical condition (such as severe hepatic impairment, pericardial disease, acute diffuse infiltrative pulmonary disease, systemic infections etc) or psychiatric illness likely to interfere with participation in this study
- Other malignancy within the past 5 years. Exceptions for the following if treated and not active: basal cell or non-metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or International Federation of Gynecology and Obstetrics Stage 1 carcinoma of the cervix.
- History of allergic reaction attributable to compounds containing boron or mannitol.
- Pregnant or breast-feeding.
- Currently enrolled in another clinical research study or has received an investigational agent for any reason within 4 weeks before randomization.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Greece5 sites
Air Forces Military Hospital of Athens Athens, Greece
Athens
METAXA Hospital, B' Pathology Department
Athens
SOTIRIA Hospital, Medical Oncology Department
Athens
University Hospital of Crete, Dep of Medical Oncology Heraklion, Greece
Heraklion
"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology
Thessaloniki
About this study
Official title: A Phase II, Open-Label Trial of Bortezomib (VELCADE®) in Combination With Gemcitabine and Cisplatin in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
The primary objective of this study is to establish the objective response rate (complete response + partial response) following treatment with VELCADE in combination with cisplatin plus gemcitabine in patients with locally advanced (Stage IIIb) or metastatic (stage IV non-small cell lung cancer (NSCLC) who have not received prior antineoplastic therapy for advanced disease
Read the detailed description
By its mechanism of action i.e., inhibiting protein degradation, VELCADE targets a wide-range of pathways that are relevant to tumor progression and therapy resistance. Preclinical data in cell lines indicate anti-tumor activity in NSCLC. Preliminary work in vivo (animal models) suggests an enhanced anti-tumor effect in combination with cytotoxic agents commonly used in the treatment of lung cancer, including gemcitabine and CPT-11 and additive tumor growth delay when combined with cisplatin or paclitaxel.
Platinum- or non-platinum- based combinations including the newer agents represent the standard front-line treatment for patients with stage IIIB/IV NSCLC. However, despite the introduction of the newer agents, the efficacy of cytotoxic chemotherapy seems to have reached a plateau. The incorporation of molecularly targeted agents in NSCLC treatment is likely to improve the treatment outcomes. Recently, an initial Phase 2 of VELCADE in combination with gemcitabine/carboplatin in the first-line treatment of NSCLC was completed. A response rate of 21% with impressive progression-free survival and overall survival rates of 5 and 11 months, respectively, were reported.
Combining VELCADE with a currently approved standard regimen such as cisplatin/gemcitabine, may lead to a better response rate, TTP, and OS than chemotherapy alone. VELCADE combined with gemcitabine and cisplatin has been shown safe in a phase I trial in patients with advanced solid tumors. The maximum tolerated dose (MTD) of VELCADE was 1 mg/m2 on either a weekly or a biweekly schedule when combined with gemcitabine 1000 mg/m2 and cisplatin 70 mg/m2. Treatment was generally well tolerated with the weekly regimen of VELCADE being associated with less myelotoxicity. Plasma pharmacokinetic profiles of gemcitabine and cisplatin were not altered by VELCADE. Interestingly enough, among 27 patients with NSCLC an encouraging response rate of 37% and disease stabilization rate of 52% was recorded.
In this trial VELCADE alone will be administered on the first treatment cycle to examine molecular correlates of VELCADE activity. Subsequent cycles will include the combination of VELCADE with cisplatin plus gemcitabine.
Data from the phase I study of VELCADE plus cisplatin/gemcitabine contributed to the selection of the drug doses for patients that will be enrolled in the current study. Specifically, the doses employed are those identified as the MTD level of the phase I study.
The anti-tumor activity of the combination of VELCADE and cisplatin/gemcitabine in the first-line treatment of NSCLC will be tested in this study according to a Simon 2-stage optimal design.
- Conditions
- Non Small Cell Lung Cancer, Metastatic
- Being tested
- Bortezomib, Gemcitabine, Cisplatin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called VELCADE 1 mg/m2 on days 1 and 8, of a 21-days treatment cycle for a maximum of 8 cycles
Velcade
GemcitabineDrug
Also called Gemzar
Gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-days treatment cycle for a maximum of 8 cycles
CisplatinDrug
Also called CDDP
Cisplatin 70 mg/m2 on day 1 of a 21-days treatment cycle for a maximum of 8 cycles
| Study group | Role | What they receive |
|---|---|---|
| Velcade/GEM/CDDP | Experimental | Bortezomib / Gemcitabine / Cisplatin Receives: Drug: Bortezomib; Drug: Gemcitabine; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Participants will be evaluated for response to the study treatment after the first three treatment cycles (cycle repeated every 21 days) and then every two treatment cycles (completion of cycles 5, 7, 9 etc.) until documentation of disease progression.
Measured: Up to 9 weeks
Secondary outcomes (3)
Progression free survival
Progression free survival will be calculated from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Measured: 1 year
Overall survival
Overall survival will be calculated from date of randomization until the date of death from any cause, assessed up to 36 months
Measured: 1 year
Number of participants with adverse events
Participants will be followed for adverse events appearance until the end of treatment administration (seven treatment cycles repeated every 21 days plus two more cycles according to psysician's decision)plus 30 more days after treatment completion.
Measured: Participants will be followed for adverse events up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2012 (estimated)
- Study startJun 2009
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital of Crete
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vassilis Georgoulias, MD, University Hospital of Crete
- Investigators
- Vassilis Georgoulias, MD, Principal investigator, University Hospital of HeraklionSofia Aggelaki, MD, Principal investigator, University Hospital of Heraklion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01633645
- Sponsor's protocol ID
- 26866138-LUC-2006
- Status last verified
- Sep 2015
- First submitted
- 13 Mar 2012
- Last updated
- 28 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-Label Trial of Bortezomib (VELCADE®) in Combination With Gemcitabine and Cisplatin in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01633645
- Acronym / sponsor ID
- 26866138-LUC-2006
- Conditions
- Non Small Cell Lung Cancer, Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- University Hospital of CreteUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 4 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to establish the objective response rate (complete response + partial response) following treatment with VELCADE in combination with cisplatin plus gemcitabine in patients with locally advanced (Stage IIIb) or metastatic (stage IV non-small cell lung cancer (NSCLC) who have not received prior antineoplastic therapy for advanced disease
Detailed description
By its mechanism of action i.e., inhibiting protein degradation, VELCADE targets a wide-range of pathways that are relevant to tumor progression and therapy resistance. Preclinical data in cell lines indicate anti-tumor activity in NSCLC. Preliminary work in vivo (animal models) suggests an enhanced anti-tumor effect in combination with cytotoxic agents commonly used in the treatment of lung cancer, including gemcitabine and CPT-11 and additive tumor growth delay when combined with cisplatin or paclitaxel.
Platinum- or non-platinum- based combinations including the newer agents represent the standard front-line treatment for patients with stage IIIB/IV NSCLC. However, despite the introduction of the newer agents, the efficacy of cytotoxic chemotherapy seems to have reached a plateau. The incorporation of molecularly targeted agents in NSCLC treatment is likely to improve the treatment outcomes. Recently, an initial Phase 2 of VELCADE in combination with gemcitabine/carboplatin in the first-line treatment of NSCLC was completed. A response rate of 21% with impressive progression-free survival and overall survival rates of 5 and 11 months, respectively, were reported.
Combining VELCADE with a currently approved standard regimen such as cisplatin/gemcitabine, may lead to a better response rate, TTP, and OS than chemotherapy alone. VELCADE combined with gemcitabine and cisplatin has been shown safe in a phase I trial in patients with advanced solid tumors. The maximum tolerated dose (MTD) of VELCADE was 1 mg/m2 on either a weekly or a biweekly schedule when combined with gemcitabine 1000 mg/m2 and cisplatin 70 mg/m2. Treatment was generally well tolerated with the weekly regimen of VELCADE being associated with less myelotoxicity. Plasma pharmacokinetic profiles of gemcitabine and cisplatin were not altered by VELCADE. Interestingly enough, among 27 patients with NSCLC an encouraging response rate of 37% and disease stabilization rate of 52% was recorded.
In this trial VELCADE alone will be administered on the first treatment cycle to examine molecular correlates of VELCADE activity. Subsequent cycles will include the combination of VELCADE with cisplatin plus gemcitabine.
Data from the phase I study of VELCADE plus cisplatin/gemcitabine contributed to the selection of the drug doses for patients that will be enrolled in the current study. Specifically, the doses employed are those identified as the MTD level of the phase I study.
The anti-tumor activity of the combination of VELCADE and cisplatin/gemcitabine in the first-line treatment of NSCLC will be tested in this study according to a Simon 2-stage optimal design.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Velcade/GEM/CDDP | Experimental | Drug: Bortezomib, Drug: Gemcitabine, Drug: CisplatinBortezomib / Gemcitabine / Cisplatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Men or women, 18 years of age or older.
- NSCLC histologically or cytologically confirmed.
- Locally advanced (Stage IIIB) or metastatic (Stage IV) NSCLC.
- No prior systemic anti-neoplastic therapy for Stage IIIB/IV NSCLC (one prior line is allowed if given as adjuvant or neo-adjuvant therapy).
- Measurable disease per RECIST criteria.
Key exclusion criteria (18 listed)
- Peripheral neuropathy of Grade 2 or greater intensity, as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE Version 3.0).
- Previous treatment with VELCADE.
- Prior systemic anti-neoplastic therapies for Stage IIIB/IV NSCLC except if as neoadjuvant therapy for Stage IIIB.
- Any prior systemic anti-neoplastic therapy for NSCLC (i.e., prior chemotherapy, radiation therapy, prior monoclonal antibodies or any investigational drug or any major surgery) within 4 weeks before enrollment.
- Significant weight loss (documented < 10% body weight in the 6 weeks before enrollment).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: VELCADE 1 mg/m2 on days 1 and 8, of a 21-days treatment cycle for a maximum of 8 cyclesVelcade | Drug | Velcade/GEM/CDDP |
| GemcitabineAlso: GemzarGemcitabine 1000 mg/m2 on days 1 and 8 of a 21-days treatment cycle for a maximum of 8 cycles | Drug | Velcade/GEM/CDDP |
| CisplatinAlso: CDDPCisplatin 70 mg/m2 on day 1 of a 21-days treatment cycle for a maximum of 8 cycles | Drug | Velcade/GEM/CDDP |
Primary outcome
Overall Response Rate
Time frame: Up to 9 weeks
Participants will be evaluated for response to the study treatment after the first three treatment cycles (cycle repeated every 21 days) and then every two treatment cycles (completion of cycles 5, 7, 9 etc.) until documentation of disease progression.
3 secondary outcomes
Progression free survival
Time frame: 1 year
Overall survival
Time frame: 1 year
Number of participants with adverse events
Time frame: Participants will be followed for adverse events up to 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vassilis Georgoulias, MD principal investigator
University Hospital of Heraklion
Sofia Aggelaki, MD principal investigator
University Hospital of Heraklion
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib, Gemcitabine and Cisplatin in people with Non Small Cell Lung Cancer and Metastatic, run by University Hospital of Crete at 5 sites in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. 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 28 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Greece. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Overall Response Rate (time frame: Up to 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Sep 2015.