Clinical Trials /

Effect of Pembrolizumab With or Without Carboplatin and Paclitaxel on Immune Response in Patients With Recurrent or Stage IIIB-IV Non-small Cell Lung Cancer

NCT02581943

Description:

This randomized pilot phase II trial studies the effect of pembrolizumab with or without carboplatin and paclitaxel on immune response in patients with non-small cell lung cancer that has come back or stage IIIB-IV. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Giving pembrolizumab together with carboplatin and paclitaxel may improve immune responses in patients with non-small cell lung cancer.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Effect of Pembrolizumab With or Without Carboplatin and Paclitaxel on Immune Response in Patients With Recurrent or Stage IIIB-IV Non-small Cell Lung Cancer
  • Official Title: Immune Response in Patients With Recurrent or Metastatic Non-small Cell Lung Cancer and Performance Status of 2 Treated With a Combination of Pembrolizumab and Low Dose Weekly Carboplatin/Paclitaxel

Clinical Trial IDs

  • ORG STUDY ID: CCCWFU 62415
  • SECONDARY ID: NCI-2015-01708
  • SECONDARY ID: CCCWFU #62415
  • SECONDARY ID: CCCWFU 62415
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT02581943

Conditions

  • Recurrent Non-Small Cell Lung Carcinoma
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV 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, RibocarboArm II (pembrolizumab, paclitaxel, carboplatin)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratArm II (pembrolizumab, paclitaxel, carboplatin)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Arm I (pembrolizumab)

Purpose

This randomized pilot phase II trial studies the effect of pembrolizumab with or without carboplatin and paclitaxel on immune response in patients with non-small cell lung cancer that has come back or stage IIIB-IV. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Giving pembrolizumab together with carboplatin and paclitaxel may improve immune responses in patients with non-small cell lung cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Determine the immune effects of single agent pembrolizumab and pembrolizumab combined
      with low-dose carboplatin and paclitaxel.

      II. Estimate the treatment response to single agent pembrolizumab and pembrolizumab combined
      with low-dose carboplatin and paclitaxel.

      SECONDARY OBJECTIVES:

      I. Determine the toxicity and tolerability of pembrolizumab and pembrolizumab combined with
      low-dose carboplatin and paclitaxel.

      II. Assess quality of life (QOL) in patients receiving single agent pembrolizumab and
      pembrolizumab combined with carboplatin and paclitaxel.

      III. Assess the association between immune response and clinical response.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1.

      ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1, paclitaxel IV over 1
      hour and carboplatin IV over 1 hour on days 1, 7 and 14.

      In both arms, courses repeat every 3 weeks for 2 years in the absence of disease progression
      or unacceptable toxicity.

      After completion of study treatment, patients are followed up for at least 30 days and then
      every 8 weeks thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
    Arm II (pembrolizumab, paclitaxel, carboplatin)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1, paclitaxel IV over 1 hour and carboplatin IV over 1 hour on days 1, 7 and 14. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
    • Carboplatin
    • Paclitaxel

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must have histologically or cytologically confirmed non-small cell lung
                 cancer (NSCLC) that is advanced/metastatic (stage IIIB/IV) or recurrent (progression
                 after surgery or radiation or chemo-radiation treatment for loco-regional disease)
    
              -  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 6 weeks (42
                 days) prior to 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; at least 4 mm of tumor
                 tissue will be needed for programmed cell death-ligand (PD-L1) staining
    
              -  Patients who have received up to two previous lines of systemic chemotherapy are
                 eligible for this trial
    
              -  At least one measurable lesion as defined by Response Evaluation Criteria in Solid
                 Tumors (RECIST) version (v)1.1 on screening computed tomography (CT) or magnetic
                 resonance imaging (MRI)
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status of 2
    
              -  White blood cell count (WBC) > 2,500 cells/mcL
    
              -  Absolute neutrophil count (ANC) >= 1,500/mcL
    
              -  Platelets >= 100,000/mcL
    
              -  Hemoglobin >= 9 g/dL
    
              -  Total bilirubin =< 2.0 x upper limit of normal (ULN)
    
              -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
                 [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
                 =< 2.5 x ULN Or =< 5 x ULN in presence of liver metastases
    
              -  Creatinine within normal institutional limits OR creatinine clearance > 50 mL/min for
                 patients with creatinine levels above institutional normal
    
              -  Potassium >= lower limit of normal
    
              -  Women of child-bearing potential and men must agree to use adequate contraception
                 (hormonal or barrier method of birth control; abstinence) for the duration of study
                 participation and for 4 weeks after the final administration of study drugs; should a
                 woman become pregnant or suspect she is pregnant while participating in this study,
                 she should inform her treating physician immediately
    
              -  Ability to understand and the willingness to sign an Institutional Review Board
                 (IRB)-approved informed consent document
    
            Exclusion Criteria:
    
              -  Known active (untreated) central nervous system (CNS) metastases that require
                 steroids; subjects with CNS metastases who have completed a course of therapy would
                 be eligible for the study provided they are clinically stable for at least 4 weeks
                 before study entry, defined as:
    
                   -  No evidence of new or enlarging CNS metastasis or new neurological symptoms
                      attributable to CNS metastases
    
                   -  Asymptomatic and receiving either no or stable doses of anticonvulsants and no
                      corticosteroids for the 4 weeks prior to study entry
    
              -  Current or previous other malignancy within 2 years of study entry, except cured
                 basal or squamous cell skin cancer, superficial bladder cancer, prostate
                 intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or
                 indolent malignancy without sponsor approval
    
              -  History of previous exposure to an anti-programmed cell death 1 (PD-1)/PD-L1 agent
    
              -  Patients receiving any other investigational agents and or more that two different
                 chemotherapy regimens for treatment of metastatic disease
    
              -  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
    
              -  History of allergic reactions attributed to compounds of similar chemical or biologic
                 composition to pembrolizumab, paclitaxel or carboplatin
    
              -  Current uncontrolled cardiac disease such as angina or myocardial infarction,
                 congestive heart failure including New York Heart Association functional
                 classification of 3, or arrhythmia requiring treatment
    
              -  History of pneumonitis or active lung infection
    
              -  Chronic or current active infectious disease requiring systemic antibiotics,
                 antifungals, or antivirals
    
              -  Patients receiving chronic steroids and or immunosuppression
    
              -  Known human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) or
                 hepatitis C virus (HCV) viremia or at risk for HBV reactivation; HBV deoxyribonucleic
                 acid (DNA) and testing for HCV ribonucleic acid (RNA) must be undetectable; at risk
                 for HBV reactivation is defined as hepatitis B surface antigen positive or
                 anti-hepatitis B core antibody positive
    
              -  History of autoimmune disease(s)
    
              -  Psychiatric illness/social situations that would limit compliance with study
                 requirements
    
              -  Any other condition or circumstance that could interfere with adherence to the
                 study's procedures or requirements, or otherwise compromise the study's objectives
                 such as history of, or any evidence of active, non-infectious pneumonitis
    
              -  Has an active infection requiring systemic therapy
    
              -  Pregnant women are excluded; breastfeeding should be discontinued prior to study
                 entry
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Duration of response
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Duration of response will also be assessed in each group and compared using survival analysis methods.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Wake Forest University Health Sciences

    Last Updated

    February 20, 2017