Non Small Cell Lung Cancer Clinical Trial
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
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.
;
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05094804 -
A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents
|
Phase 1/Phase 2 | |
Recruiting |
NCT05707286 -
Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
|
||
Recruiting |
NCT04258137 -
Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study
|
N/A | |
Completed |
NCT01945021 -
Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC
|
Phase 2 | |
Completed |
NCT04487457 -
Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
|
||
Terminated |
NCT04022876 -
A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection)
|
Phase 1 | |
Recruiting |
NCT05898763 -
TEIPP Immunotherapy in Patients With NSCLC
|
Phase 1/Phase 2 | |
Recruiting |
NCT05532696 -
Phase 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients
|
Phase 1/Phase 2 | |
Completed |
NCT04311034 -
A Study of RC48-ADC in Subjects With Advanced Non-small Cell Lung Cancer
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT03177291 -
Pirfenidone Combined With Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC
|
Phase 1 | |
Terminated |
NCT03257722 -
Pembrolizumab + Idelalisib for Lung Cancer Study
|
Phase 1/Phase 2 | |
Completed |
NCT00349089 -
Trial on Refinement of Early Stage Lung Cancer Adjuvant Therapy
|
Phase 2 | |
Completed |
NCT05116891 -
A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT04571632 -
Clinical Trial of SBRT and Systemic Pembrolizumab With or Without Avelumab/Ipilimumab+ Dendritic Cells in Solid Tumors
|
Phase 2 | |
Terminated |
NCT03599518 -
DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer
|
Phase 1 | |
Not yet recruiting |
NCT06020989 -
Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy
|
Phase 2 | |
Withdrawn |
NCT03982134 -
PDR001 + Panobinostat for Melanoma and NSCLC
|
Phase 1 | |
Withdrawn |
NCT03574649 -
QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer
|
Phase 2 | |
Withdrawn |
NCT02844140 -
DE-CT in Lung Cancer Proton Therapy
|
N/A | |
Completed |
NCT03780010 -
Study of TRC105 + Paclitaxel/Carboplatin and Bevacizumab in Patients With NSCLC
|
Phase 1 |