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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (actual)
• Sponsor: University Hospital of Crete · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 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.

Conditions

• Non Small Cell Lung Cancer
• Metastatic

Interventions

Type	Name	Description
DRUG	Bortezomib	Velcade
DRUG	Gemcitabine	Gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-days treatment cycle for a maximum of 8 cycles
DRUG	Cisplatin	Cisplatin 70 mg/m2 on day 1 of a 21-days treatment cycle for a maximum of 8 cycles

Timeline

• Start date: 2009-06-01
• Primary completion: 2013-04-01
• Completion: 2013-04-01
• First posted: 2012-07-04
• Last updated: 2015-09-28

Locations

5 sites across 1 country: Greece