Clinical Trials /

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

NCT02621398

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Stage II-IIIB Non-Small Cell Lung Cancer
  • Official Title: Moving PD-1 Blockade With Pembrolizumab Into Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 031507
  • SECONDARY ID: NCI-2015-01810
  • SECONDARY ID: 031507
  • SECONDARY ID: P30CA072720
  • NCT ID: NCT02621398

Conditions

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

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (paclitaxel, carboplatin, radiation, pembrolizumab)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratTreatment (paclitaxel, carboplatin, radiation, pembrolizumab)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)ExperimentalPatients 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.
  • Carboplatin
  • Paclitaxel
  • Pembrolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure: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
Safety Issue:
Description:Response rates will be compared to historical results.
Measure:Local survival
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Metastasis-free survival
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Progression free survival according RECIST 1.1 and immune-related Response Evaluation Criteria In Solid Tumors
Time Frame:Up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rutgers, The State University of New Jersey

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