Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)
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|ClinicalTrials.gov Identifier: NCT02812667|
Recruitment Status : Recruiting
First Posted : June 24, 2016
Last Update Posted : August 7, 2018
The purpose of the study is to determine whether plinabulin (also known as BPI-2358) has an effect on cancer and body in combination with nivolumab, a standard treatment for metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy.
Plinabulin inhibits tumor growth by targeting both new and existing blood vessels going to the tumor as well as killing tumor cells. Plinabulin is an investigational drug, a drug that is not approved for use outside of research studies by regulatory agencies. Up to 38 patients will be enrolled.
|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer Metastatic||Drug: Nivolumab + Plinabulin||Phase 1|
Plinabulin is a microtubule destabilizing agent (MDA) that inhibits the polymerization of tubulin monomers with resultant vascular disrupting properties. Plinabulin inhibits tumor growth by targeting both angiogenesis and tumor vasculature as well as directly by inducing apoptosis via the Ras-JNK pathway. It also may activate anti-tumor immunity via inducing maturation of dendritic cells (DC) and triggering release of pro-inflammatory cytokines. Plinabulin could therefore have a synergic anti-tumor effect when combined with immune-checkpoint inhibitors. This hypothesis has been confirmed in a murine model bearing subcutaneous MC38 colon cancers using other MDAs, including ansamitocin P3, which induces DC maturation similar to that of plinabulin. Plinabulin has been tested in a randomized phase 2 trial in combination of docetaxel and showed similar response rate to that of docetaxel alone, but with a significantly longer duration of response.
Nivolumab is an inhibitor of the programmed cell death receptor-1 checkpoint pathway (PD-1) that has superior activity in NSCLC, regardless of tumor histology, comparing to standard of care. In this study, we plan to combine nivolumab with escalating doses of plinabulin to determine the maximum tolerated dose (MTD) and /or recommended Phase 2 dose (RP2D) of the combination. An expansion cohort will be enrolled at RP2D to further assess toxicities and to evaluate preliminary anti-tumor activity.
This is a single-center, phase 1 dose finding trial of plinabulin, combining with FDA approved dose of nivolumab, using a 3+3 design in patients with metastatic NSCLC who progressed after chemotherapy, including a platinum-containing regimen. Patients will receive plinabulin at escalating doses in combination with nivolumab. Doses of plinabulin and nivolumab will be administered as intravenous infusions in 4-week cycles. Patients will receive both medications on Days 1 and 15 and additional dose of plinabulin on Day 8. Plinabulin will be administered 60 minutes after the completion of nivolumab.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Nivolumab in Combination With Escalating Doses of Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)|
|Actual Study Start Date :||August 29, 2016|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2020|
Experimental: Nivolumab + Plinabulin
Nivolumab 240mg IV, day 1 and 15 until disease progression Plinabulin 3.5mg/m2, 20mg/m2, 30 mg/m2 or 40mg/m2 IV, day 1,8 and 15 until disease progression
Drug: Nivolumab + Plinabulin
- Maximum tolerated dose (MTD) [ Time Frame: 2 years ]
- Frequency and severity of treatment-related adverse events as assessed by CTCAE v4. [ Time Frame: 2 years ]
- Objective response rate (ORR) [ Time Frame: 2 years ]
- Disease control rate (DCR) [ Time Frame: 2 years ]
- Progression free survival (PFS) [ Time Frame: 2 years ]
- Overall survival (OS) [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02812667
|Contact: Lyudmilla Bazhenova, MDfirstname.lastname@example.org|
|United States, California|
|UC San Diego Moores Cancer Center||Recruiting|
|La Jolla, California, United States, 92093|
|Contact: Lyudmilla Bazhenova, MD 858-534-1765 email@example.com|
|Principal Investigator:||Lyudmilla Bazhenova, MD||University of California, San Diego|