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

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: NCT02621398
Recruitment Status : Active, not recruiting
First Posted : December 3, 2015
Last Update Posted : September 23, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Salma Jabbour, MD, Rutgers Cancer Institute of New Jersey

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.

Condition or disease Intervention/treatment Phase
Stage II Non-Small Cell Lung Cancer Stage IIIA Non-Small Cell Lung Cancer Stage IIIB Non-Small Cell Lung Cancer Radiation: 3-Dimensional Conformal Radiation Therapy Drug: Carboplatin Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Drug: Paclitaxel Biological: Pembrolizumab Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess safety and toxicity of anti-programmed cell death 1 (PD-1) inhibition with pembrolizumab with concurrent chemoradiation therapy for non-operable, locally advanced non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. To evaluate local control and distant metastasis-free survival, progression-free and overall survival with the addition of pembrolizumab to chemoradiotherapy.

II. To evaluate the rates of pneumonitis that may result from combination pembrolizumab and chemoradiotherapy.

TERTIARY OBJECTIVES:

I. To assess whether programmed cell death ligand 1 (PDL1) status on immunohistochemistry is predictive of response to pembrolizumab when combined with chemoradiation therapy.

II. To assess T cell (cluster of differentiation 8 positive [CD8+] T cells and CD4+ forkhead box P3 positive [FoxP3+] regulatory cells) responses at weeks 1, 3, 6 during chemoradiation therapy and before each administration of pembrolizumab for cycles 1, 2, 3.

OUTLINE: This is a dose-escalation study of pembrolizumab.

Patients receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients undergo 3-dimensional (3D) conformal radiation therapy (CRT) or intensity-modulated radiation therapy (IMRT) once daily (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.

After completion of study treatment, patients are followed up at 30 days every 12 weeks for 1 year, every 16 weeks for 1 year, every 6 months for 3 years, and then annually thereafter.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Moving PD-1 Blockade With Pembrolizumab Into Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer
Actual Study Start Date : April 11, 2016
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)
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
Undergo 3D-CRT or IMRT
Other Names:
  • 3-dimensional radiation therapy
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Radiation: Intensity-Modulated Radiation Therapy
Undergo 3D-CRT or IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  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 [ Time Frame: Up to 30 days ]
    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.


Secondary Outcome Measures :
  1. Best overall response according to RECIST 1.1 [ Time Frame: Time from the start of the treatment until disease progression/recurrence, assessed up to 5 years ]
    Response rates will be compared to historical results.

  2. Local survival [ Time Frame: Up to 5 years ]
  3. Metastasis-free survival [ Time Frame: Up to 5 years ]
  4. Overall survival [ Time Frame: Up to 5 years ]
  5. Progression free survival according RECIST 1.1 and immune-related Response Evaluation Criteria In Solid Tumors [ Time Frame: Up to 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Women of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Women of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Exclusion Criteria:

  • 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
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti- programmed cell death 1 ligand 2 (PD-L2) agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (HCV) (e.g., HCV ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy
  • Pleural effusion that cannot be controlled despite appropriate interventions
  • History of allergy or hypersensitivity to any component of the treatment
  • No active second cancers

Information from the National Library of Medicine

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): NCT02621398


Locations
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United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06510
United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, Pennsylvania
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Rutgers, The State University of New Jersey
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Salma Jabbour, MD Rutgers Cancer Institute of New Jersey

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Salma Jabbour, MD, Professor, Radiation Oncology, Rutgers Cancer Institute of New Jersey
ClinicalTrials.gov Identifier: NCT02621398    
Other Study ID Numbers: 031507
NCI-2015-01810 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
031507 ( Other Identifier: Rutgers Cancer Institute of New Jersey )
P30CA072720 ( U.S. NIH Grant/Contract )
First Posted: December 3, 2015    Key Record Dates
Last Update Posted: September 23, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Carboplatin
Pembrolizumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological