Bortezomib in Combination With Gemcitabine and Cisplatin in 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
Non Small Cell Lung Cancer
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Overall Response Rate [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]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.
- Progression free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]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
- Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]Overall survival will be calculated from date of randomization until the date of death from any cause, assessed up to 36 months
- Number of participants with adverse events [ Time Frame: Participants will be followed for adverse events up to 24 weeks ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||June 2009|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Bortezomib / Gemcitabine / Cisplatin
Other Name: VELCADE 1 mg/m2 on days 1 and 8, of a 21-days treatment cycle for a maximum of 8 cyclesDrug: Gemcitabine
Gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-days treatment cycle for a maximum of 8 cycles
Other Name: GemzarDrug: Cisplatin
Cisplatin 70 mg/m2 on day 1 of a 21-days treatment cycle for a maximum of 8 cycles
Other Name: CDDP
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.
|Contact: Vassilis Georgoulias, MDemail@example.com|
|Contact: Sofia Aggelaki, MDfirstname.lastname@example.org|
|Air Forces Military Hospital of Athens Athens, Greece||Recruiting|
|Contact: Nikos Kentepozidis, MD email@example.com|
|Principal Investigator: Nikos Kentepozidis, MD|
|SOTIRIA Hospital, Medical Oncology Department||Recruiting|
|Contact: Konstantinos Sirigos firstname.lastname@example.org|
|Principal Investigator: Konstantinos Sirigos, MD|
|METAXA Hospital, B' Pathology Department||Recruiting|
|Contact: Nikolaos Ziras, MD|
|Principal Investigator: Nikolaos Ziras, MD|
|University Hospital of Crete, Dep of Medical Oncology Heraklion, Greece||Recruiting|
|Contact: Dora Hatzidaki +302810938570 email@example.com|
|Contact: Ioannis Athanasakis +302810392783 firstname.lastname@example.org|
|Principal Investigator: Vassilis Georgoulias, MD|
|"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology||Recruiting|
|Contact: Ioannis Boukovinas, MD email@example.com|
|Principal Investigator: Ioannis Boukovinas, MD|
|Principal Investigator:||Vassilis Georgoulias, MD||University Hospital of Heraklion|
|Principal Investigator:||Sofia Aggelaki, MD||University Hospital of Heraklion|