- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01633645
Bortezomib in Combination With Gemcitabine and Cisplatin in Advanced or Metastatic Non-Small Cell Lung Cancer
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Athens, Greece
- Air Forces Military Hospital of Athens Athens, Greece
-
Athens, Greece
- SOTIRIA Hospital, Medical Oncology Department
-
Athens, Greece
- METAXA Hospital, B' Pathology Department
-
Heraklion, Greece
- University Hospital of Crete, Dep of Medical Oncology Heraklion, Greece
-
Thessaloniki, Greece
- "Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Velcade/GEM/CDDP
Bortezomib / Gemcitabine / Cisplatin
|
Velcade
Other Names:
Gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-days treatment cycle for a maximum of 8 cycles
Other Names:
Cisplatin 70 mg/m2 on day 1 of a 21-days treatment cycle for a maximum of 8 cycles
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 9 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival
Time Frame: 1 year
|
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
|
1 year
|
Overall survival
Time Frame: 1 year
|
Overall survival will be calculated from date of randomization until the date of death from any cause, assessed up to 36 months
|
1 year
|
Number of participants with adverse events
Time Frame: Participants will be followed for adverse events up to 24 weeks
|
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.
|
Participants will be followed for adverse events up to 24 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Vassilis Georgoulias, MD, University Hospital Of Heraklion
- Principal Investigator: Sofia Aggelaki, MD, University Hospital Of Heraklion
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
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gemcitabine
- Bortezomib
Other Study ID Numbers
- 26866138-LUC-2006
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 Non Small Cell Lung Cancer
-
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 California, San FranciscoAstraZenecaActive, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Cancer | Stage IB Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Cancer | Stage IIB Non-Small Cell Lung CancerUnited States
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
AIO-Studien-gGmbHBristol-Myers Squibb; Eli Lilly and Company; Merck Sharp & Dohme LLC; Pfizer; Gilead... and other collaboratorsRecruitingSmall-cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage I | Metastatic Non-small Cell Lung Cancer (NSCLC) | Non Small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer Stage IIGermany
-
Alexander ChiNot yet recruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Carcinoma | Non-small Cell Lung Cancer Stage IIChina
-
National Cancer Institute (NCI)Not yet recruitingStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerCanada
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
-
Karen KellyBristol-Myers Squibb; National Cancer Institute (NCI); TransgeneCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung CancerUnited States
-
Memorial Sloan Kettering Cancer CenterAstraZenecaRecruitingNSCLC | Lung Cancer | Non-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | PD-L1 Gene Mutation | Non-small Cell Lung Cancer Stage IIIA | Non-small Cell Lung Cancer Stage IIUnited States
-
Virginia Commonwealth UniversityNational Cancer Institute (NCI)WithdrawnStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited 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