Neoadjuvant Chemoradiation Plus Pembrolizumab Followed By Consolidation Pembrolizumab in NSCLC
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02987998|
Recruitment Status : Active, not recruiting
First Posted : December 9, 2016
Last Update Posted : June 30, 2020
The purpose of this study is to determine the feasibility and evaluate the safety of delivering chemoradiotherapy, the usual approach to non-small cell lung cancer, in combination with pembrolizumab (MK-3745), followed by consolidation pembrolizumab after surgical resection. Consolidation therapy is treatment given following the initial treatment.
Pembrolizumab is an investigational drug (also known as Keytruda), which has been approved by the FDA for use in certain types of skin cancer (melanoma), and for use in certain types of head and neck cancer. However, it has not been approved for use in other cancers such as non-small cell lung cancer (NSCLC). Pembrolizumab is a monoclonal antibody that binds to the surface of some cells of the immune system and activates them against cancer cells. It is not chemotherapy.
|Condition or disease||Intervention/treatment||Phase|
|Stage IIIA Non-Small Cell Lung Cancer||Drug: Cisplatin Drug: Etoposide Drug: Pembrolizumab Drug: Radiation||Phase 1|
The primary hypothesis is that the addition of pembrolizumab to neoadjuvant concurrent chemoradiation, followed by consolidation pembrolizumab, will be safe and feasible to deliver to patients with resectable stage 3A Non-small cell lung cancer (NSCLC).
This study also plans to observe the efficacy of this combination in the overall and biomarker-positive population.
Primary Objective Primary objective of this phase 1 study is to determine safety and feasibility of MK3475 with standard of care therapy of chemotherapy with radiation for newly diagnosed stage 3 lung carcinoma.
• To define the Safety, tolerability and feasibility of MK3475 in combination with chemotherapy with cisplatin and etoposide along with 45 Gy of radiation in newly diagnosed stage 3 non-small cell lung carcinoma.
- Progression Free Survival
- Objective response rate,
- Complete pathologic response rate,
- Nodal downstaging at surgery,
- Overall survival,
- Safety and tolerability
Correlative Objective(s) Exploratory objectives: Overall response rate, progression free survival, overall survival in Programmed death-ligand (PDL-1) positive versus negative subgroups
Study Design This is an open-label, single arm phase I trial of neoadjuvant chemotherapy + pembrolizumab with concurrent radiation followed by surgical resection and consolidation pembrolizumab in resectable stage 3A (N2+) NSCLC.
Eligible patients will have biopsy-confirmed T1-3N2M0 (stage IIIA) non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, or large cell/NSCLC not otherwise specified), performance status 0-1, adequate lung function and deemed medically resectable by a thoracic surgeon, adequate organ function for chemotherapy, and no contraindications to pembrolizumab (i.e. autoimmune disorders or underlying pulmonary fibrosis).
Because pembrolizumab has been safely added to multiple platinum doublet chemotherapy regimens in lung cancer but not yet tested in the setting of concurrent radiation, we plan to evaluate safety and feasibility of the combination therapy. 10 patients will be enrolled at the full starting dose of all 3 agents. If 3 or more (>30%) have grade 3 or higher pulmonary toxicity or any grade 4 nonhematologic toxicity, the study will be stopped. If 2 or fewer have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then an additional 10 will be enrolled. If 5 or fewer (<25%) of the 20 patients have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then this regimen will be deemed safe and feasible for further study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Safety and Feasibility Study of Neoadjuvant Chemoradiation Plus Pembrolizumab Followed By Consolidation Pembrolizumab in Resectable Stage 3A Non-Small Cell Lung Cancer|
|Actual Study Start Date :||May 18, 2017|
|Estimated Primary Completion Date :||January 24, 2024|
|Estimated Study Completion Date :||January 24, 2024|
Experimental: Resectable Patients
Chemoradiation (Cisplatin + Etoposide + Pembrolizumab with concurrent radiation). Patients will be assessed for surgery followed by consolidation therapy
Cisplatin (50mg/m2 IV D1, 8, 29, 36)
Etoposide (50mg/m2 IV D1-5, 29-33)
Pembrolizumab (200mg IV D1, 21, 42)
Radiation (1.8Gy/D to 45Gy in 25 fractions)
- Number of patients with grade 3 pulmonary toxicity or grade 4 other non hematologic toxicity [ Time Frame: Up to 5 years ]If 5 or fewer (<25%) of the 20 patients have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then this regimen will be deemed safe and feasible for further study
- Progression Free Survival [ Time Frame: Up to 5 years ]Time from beginning of treatment to progression, death, or five years, whichever came first. Progression is defined as Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm
- Objective Response Rate [ Time Frame: Up to 5 years ]Number of patients with objective response (CR + PR) where complete response is defined as Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. And Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Complete Pathologic Response Rate [ Time Frame: Up to 5 years ]Pathological complete response is defined as absence of foci of tumor cells at the local site (pCR)
- Nodal Downstaging at Surgery [ Time Frame: Up to 4 weeks after induction treatment ]Number of patients with reduced stages in nodes at surgery
- Overall Survival [ Time Frame: Up to 5 years ]Time from beginning of treatment to death or 5 year, whichever comes first
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): NCT02987998
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Nathan Pennell, MD, PhD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|