Pembrolizumab, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Stage II-IIIB Non-Small Cell Lung Cancer

NCT02621398 | Completed Phase 1 Results DMC

• 4 other identifiers: 031507NCI-2015-01810Pro20150002247P30CA072720
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects, best dose, and best way to give pembrolizumab when given together with paclitaxel, carboplatin, and radiation therapy in treating patients with stage II-IIIB non-small cell lung cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab together with paclitaxel, carboplatin, and radiation therapy may kill more tumor cells.

Conditions

Stage II Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of the Combination of Pembrolizumab With Paclitaxel, Carboplatin and Radiation Therapy According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  The 3+3 algorithm design will be used to find the MTD. Safety will be evaluated by DLT, defined as grade 4 pneumonitis. Toxicities will be characterized based on seriousness, causality, toxicity grading, and action taken with regard to trial treatment.

  Up to 30 days

Secondary Outcomes (5)

• Overall Survival as Measured by the Kaplan Meier Estimation Method

  Time of initiation of chemoradiation through study completion (death)

• Best Overall Response According to Response Evaluation Criteria in Solid Tumors RECIST 1.1

  Time of initiation of chemoradiation through study completion (death)

• Metastasis-free Survival as Measured by the Kaplan Meier Estimation Method

  Time of initiation of chemoradiation through study completion (death)

• Progression Free Survival According Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and as Measured by the Kaplan Meier Estimation Method

  Time of initiation of chemoradiation through study completion (death)

• Immune-related Response Evaluation Criteria In Solid Tumors Using Immune-Related Response (irRC).

  Time of initiation of chemoradiation through study completion (death)

Study Arms (1)

Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)

EXPERIMENTAL

Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients undergo 3D CRT or IMRT QD 5 days a week for 6 weeks. Beginning 2-6 weeks after, 2 weeks before the end, or at the start of chemotherapy and radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Carboplatin; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Biological: Pembrolizumab

Interventions

3-Dimensional Conformal Radiation Therapy RADIATION

Undergo 3D-CRT or IMRT

Also known as: 3-dimensional radiation therapy, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy

Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)

Intensity-Modulated Radiation Therapy RADIATION

Undergo 3D-CRT or IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and Health Insurance Portability and Accountability Act (HIPPA) authorization for release of personal health information
• Subjects with any kind of non-small cell lung carcinoma (NSCLC) histology documented by histology or cytology from bronchial brushing or washing, or needle aspiration of a defined lesion but not from sputum cytology alone
• Must have American Joint Committee on Cancer (AJCC) 7th edition (ed) inoperable stage II disease requiring chemoradiation therapy or stage IIIA or IIIB NSCLC based on appropriate staging studies including brain magnetic resonance imaging (MRI) or head computed tomography (CT), CT chest, and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 8 weeks (56 days) before initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor or may undergo fine needle aspiration
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before registration for protocol therapy
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance rate \[CrCl\]) =\< 1.5 X upper limit of normal (ULN) OR \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Forced expiratory volume \>= 1.0 L or \>= 40% of predicted with or without bronchodilators by pulmonary function testing

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment
• Has a known history of active Bacillus tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may not participate
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator
• Rutgers Cancer Institute of New Jersey: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Jabbour SK, Berman AT, Decker RH, Lin Y, Feigenberg SJ, Gettinger SN, Aggarwal C, Langer CJ, Simone CB 2nd, Bradley JD, Aisner J, Malhotra J. Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial. JAMA Oncol. 2020 Jun 1;6(6):848-855. doi: 10.1001/jamaoncol.2019.6731.

  PMID: 32077891 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy, Conformal; Carboplatin; Radiotherapy, Intensity-Modulated; Paclitaxel; Taxes; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Limitations and Caveats

Aside from the use of only one chemotherapy doublet regimen, other limitations of this study are the small sample size and limited follow-up duration. This study, although multi institutional, was performed at only three institutions. Also, participants may have received photon therapy or proton therapy.

Results Point of Contact

• Title: Salma Jabbour, MD
• Organization: Cancer Institute of New Jersey

jabbousk@cinj.rutgers.edu

732-235-8675

Study Officials

• Salma Jabbour, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Radiation Oncology

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 3, 2015
• Study Start: August 4, 2016
• Primary Completion: October 24, 2019
• Study Completion: February 29, 2024
• Last Updated: December 16, 2025
• Results First Posted: October 11, 2023

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)