Clinical Trials /

Pembrolizumab in Treating Patients With Stage I-II Non-Small Cell Lung Cancer or High-Risk Pulmonary Nodules

NCT03634241

Description:

This phase II trial studies how well pembrolizumab works in treating patients with stage I-II non-small cell lung cancer or high-risk pulmonary nodules. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Participants With Stage I-II Non-Small Cell Lung Cancer or High-Risk Pulmonary Nodules
  • Official Title: Randomized Phase II of Immunotherapy With Pembrolizumab for the Prevention of Lung Cancer (IMPRINT-Lung)

Clinical Trial IDs

  • ORG STUDY ID: 2018-0366
  • SECONDARY ID: NCI-2018-01588
  • SECONDARY ID: 2018-0366
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03634241

Conditions

  • Lung Non-Small Cell Carcinoma
  • Pulmonary Nodule
  • Stage I Lung Cancer AJCC v8
  • Stage IA1 Lung Cancer AJCC v8
  • Stage IA2 Lung Cancer AJCC v8
  • Stage IA3 Lung Cancer AJCC v8
  • Stage IB Lung Cancer AJCC v8
  • Stage II Lung Cancer AJCC v8
  • Stage IIA Lung Cancer AJCC v8
  • Stage IIB Lung Cancer AJCC v8

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Arm B (pembrolizumab)

Purpose

This phase II trial studies how well pembrolizumab works in treating participants with stage I-II non-small cell lung cancer or high-risk pulmonary nodules. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine whether immune checkpoint blockade using pembrolizumab eliminates persistent
      (on two computed tomography [CT] scans at least 3 months apart with no evidence of shrinkage
      or regression) high-risk indeterminate pulmonary nodules (IPNs).

      SECONDARY OBJECTIVES:

      I. To determine whether immune checkpoint blockade using pembrolizumab decreases the
      incidence of lung cancers confirmed by histology (biopsy or resection).

      II. To determine whether immune checkpoint blockade using pembrolizumab prolongs cancer free
      survival (disease free survival) ([DFS]) compared with observation in patients with high-risk
      IPNs.

      III. To determine whether immune checkpoint blockade using pembrolizumab prolongs lung
      cancer-specific survival compared with observation in patients with high-risk IPNs.

      IV. To determine whether immune checkpoint blockade using pembrolizumab prolongs overall
      survival (OS) compared with observation in patients with high-risk IPNs.

      V. To assess the safety and tolerability of pembrolizumab in patients with high-risk IPNs.

      VI. To assess quality of life patient reported outcomes in patients treated with
      pembrolizumab compared with patients under observation.

      VII. To determine whether immune checkpoint blockade using pembrolizumab decreases the solid
      component of high-risk IPNs.

      EXPLORATORY OBJECTIVES:

      I. To explore the radiographic (including radiomic features) evolution of high-risk IPNs with
      and without treatment of pembrolizumab and to assess their association with risks of risk of
      lung cancer as well as their association with clinical benefit/toxicities in patients treated
      with pembrolizumab.

      II. To explore the germline deoxyribonucleic acid (DNA) profile and genomic evolution of
      circulating tumor DNA (ctDNA) of patients with high-risk IPNs and assess their association
      with risks of risk of lung cancer as well as their association with clinical
      benefit/toxicities in patients treated with pembrolizumab.

      III. To explore the T cell receptor (TCR) repertoire evolution of patients with high-risk
      IPNs and assess their association with risks of risks of lung cancer as well as their
      association with clinical benefit/toxicities in patients treated with pembrolizumab.

      IV. To explore the evolution of serum soluble factors, such as IFN-gamma and interferon
      inducible factors (such as CXCL9 and CXCL10), IL-12, TNFa, IL-10, TGF-a, VEGF, IL-6, IL-8,
      IL-17, IL-18, C-reactive protein etc. and assess their association with risks of risks of
      lung cancer as well as their association with clinical benefit/toxicities in patients treated
      with pembrolizumab.

      V. To explore the evolution of immunophenotyping or characterization of the immune cell
      subsets in the periphery, including, but not limited to, T cells, B cells, NK cells, or
      subpopulations of the aforementioned immune cell types and assess their association with
      risks of risks of lung cancer as well as their association with clinical benefit/toxicities
      in patients treated with pembrolizumab.

      OUTLINE: Participants are randomized to 1 of 2 arms.

      ARM A: Participants receive standard of care.

      ARM B: Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1.
      Courses repeat every 3 weeks for up to 4 courses in the absence of disease progression or
      unacceptable toxicity.

      After conclusion of study treatment, participants are followed up at 30 days, at 1.5, 3, and
      6 months, and then every 12 weeks thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (standard of care)Active ComparatorParticipants receive standard of care.
    Arm B (pembrolizumab)ExperimentalParticipants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
    • Pembrolizumab

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients are eligible to be included in the study only if one of the following
                 criteria applies:
    
                   -  1(a) Patients with no history of lung cancer, who have IPNs detected by low dose
                      CT (LDCT)-guided lung cancer screening or imaging studies for other reasons
                      (incidentalomas) with 15-30% cancer probability by Brock University cancer
                      prediction equation as following
    
                   -  1(b) Patients with no history of lung cancer, who have IPNs detected by
                      LDCT-guided lung cancer screening or imaging studies for other reasons
                      (incidentalomas) with > 30% cancer probability by Brock University cancer
                      prediction equation as following, but biopsy is negative for malignancy
    
                   -  1(c) Patients with history of stage I-II non-small cell lung cancer (NSCLC), who
                      have completed surgical resection or curative intent and adjuvant chemotherapy if
                      applicable, who have persistent IPNs (on two CT scans at least 3 months apart
                      with no evidence of shrinkage or regression) with 10-20% cancer probability by
                      Brock University cancer prediction equation as following
    
                   -  1(d) Patients with history of stage I-II NSCLC, who have completed surgical
                      resection of curative intent and adjuvant chemotherapy if applicable, who have
                      persistent IPNs (on two CT scans at least 3 months apart with no evidence of
                      shrinkage or regression) with 20% cancer probability by Brock University cancer
                      prediction equation as following, but biopsy is negative for malignancy
    
                   -  Brock University cancer prediction equation. This calculator estimates the
                      probability that a lung nodule described above will be diagnosed as cancer within
                      a two to four year follow-up period. Equation parameters, such as sex, have two
                      or more discrete values that may be used in the calculation.
    
              -  A male participant must agree to use a contraception during the treatment period and
                 for at least 12 weeks while receiving pembrolizumab plus an additional 120 days (a
                 spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose
                 after the last dose of study treatment and refrain from donating sperm during this
                 period.
    
              -  A female participant is eligible to participate if she is not pregnant, not
                 breastfeeding, and at least one of the following conditions applies: a) Not a woman of
                 childbearing potential (WOCBP) or b) A WOCBP who agrees to follow the contraceptive
                 guidance during the treatment period and for at least 120 days for the study treatment
    
            with risk of genotoxicity after the last dose of study treatment.
    
              -  The participant (or legally acceptable representative if applicable) provides written
                 informed consent for the trial.
    
              -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
                 Evaluation of ECOG is to be performed within 7 days prior to the date of
                 allocation/randomization.
    
              -  Absolute neutrophil count (ANC) >= 1500 per microliter (within 10 days prior to the
                 start of study treatment).
    
              -  Platelets >= 100,000 per microliter (within 10 days prior to the start of study
                 treatment).
    
              -  Hemoglobin >= 9.0 grams per microliter or >= 5.6 millimoles/liter (within 10 days
                 prior to the start of study treatment) (*criteria must be met without erythropoietin
                 dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks).
    
              -  Creatinine OR measured or calculated creatinine clearance (glomerular filtration rate
                 [GFR] can also be used in place of creatinine or creatinine clearance [CrCL]) =< 1.5 x
                 ULN OR >= 30 milliliters per minute (min) for participant with creatinine levels > 1.5
                 x institutional upper limit of normal (ULN) (creatinine clearance (CrCl) should be
                 calculated per institutional standard.) (within 10 days prior to the start of study
                 treatment).
    
              -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< for participants with total
                 bilirubin levels > 1.5 x ULN (within 10 days prior to the start of study treatment).
    
              -  Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and
                 alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 x
                 ULN (within 10 days prior to the start of study treatment).
    
              -  International normalized ratio (INR) OR prothrombin time (PT), activated partial
                 thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant
                 therapy as long as PT or aPTT is within therapeutic range of intended use of
                 anticoagulants (within 10 days prior to the start of study treatment).
    
            Exclusion Criteria:
    
              -  A WOCBP who has a positive urine pregnancy test within 72 hours prior to
                 randomization. If the urine test is positive or cannot be confirmed as negative, a
                 serum pregnancy test will be required.
    
                   -  Note: in the event that 72 hours have elapsed between the screening pregnancy
                      test and the first dose of the study treatment, another pregnancy test (urine or
                      serum) must be performed and must be negative in order for subject to start
                      receiving study medication.
    
              -  Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an
                 agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4,
                 OX-40, CD137).
    
              -  Has received prior system anti-cancer therapy including investigational agents within
                 4 weeks (could consider shorter interval for kinase inhibitors or other short
                 half-life drugs) prior to randomization.
    
                   -  Note: Participants must have recovered from all adverse events (AEs) due to
                      previous therapies to =< grade 1 or baseline. Participants with =< grade 2
                      neuropathy may be eligible.
    
                   -  Note: If participant received major surgery, they must have recovered adequately
                      from the toxicity and/or complications from the intervention prior to starting
                      study treatment.
    
              -  Has received prior radiotherapy.
    
              -  Has received a live vaccine within 30 days prior to the first dose of study drug.
                 Examples of live vaccines include, but are not limited to, the following: measles,
                 mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
                 Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
                 are generally killed virus vaccines and are allowed; however, intranasal influenza
                 vaccines (e.g., Flumist) are live attenuated vaccines and are not allowed.
    
              -  Is currently participating in or has participated in a study of investigational agent
                 or has used an investigational device within 4 weeks prior to the first dose of study
                 treatment.
    
                   -  Note: Participants who have entered the follow-up phase of an investigational
                      study may participate as long as it has been 4 weeks after the last dose of the
                      previous investigational agent.
    
              -  Has a diagnosis of immunodeficiency or is receiving chronic system steroid therapy (in
                 dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
                 immunosuppressive therapy within 7 days prior to the first dose of study drug.
    
              -  Has a known additional malignancy that is progressing or has required active treatment
                 within the past 2 years.
    
                   -  Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma
                      of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in
                      situ) that have undergone potentially curative therapy are not excluded.
    
              -  Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its
                 excipients.
    
              -  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 (e.g., thyroxine, insulin, or physiologic corticosteroid
                 replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
                 form of systemic treatment.
    
              -  Has a history of (non-infectious) pneumonitis that required steroids or has current
                 pneumonitis.
    
              -  Has an active infection requiring systemic therapy.
    
              -  Has a known history of human immunodeficiency virus (HIV).
    
              -  Has a known history of hepatitis B (defined as hepatitis B surface antigens [HBsAg]
                 reactive) or
    
            known active hepatitis C (defined as hepatitis C virus [HCV] ribonucleic acid [RNA]
            [qualitative] is detected) infection.
    
              -  Note: No testing for hepatitis B and hepatitis C is required unless mandated by local
                 health authority.
    
                   -  Has a known history of active TB (Bacillus tuberculosis).
    
                   -  Has a history or current evidence of any condition, therapy, or laboratory
                      abnormality that might confound the results of the study, interfere with the
                      subject's participation for the full duration of the study, 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 the
                      cooperation with requirements of the trial.
    
                   -  Is pregnant or breastfeeding, or expecting to conceive or father children within
                      the projected duration of the study, starting with the screening visit through
                      120 days after the last dose of trial treatment.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:Accepts Healthy Volunteers

    Primary Outcome Measures

    Measure:Regression rate of high-risk indeterminate pulmonary nodules (IPNs)
    Time Frame:At 6 months
    Safety Issue:
    Description:This will be estimated by the Kaplan-Meier method.

    Secondary Outcome Measures

    Measure:Incidence of lung cancer
    Time Frame:Up to 6 months
    Safety Issue:
    Description:This will be estimated by the Kaplan-Meier method.
    Measure:Cancer-free survival
    Time Frame:Up to 6 months
    Safety Issue:
    Description:Stratified log-rank test will be used to compare cancer-free survival between treatment groups. The Cox (proportional hazards) regression model will be used to incorporate potential prognostic factors and treatment assignments as covariates.
    Measure:Lung cancer-specific survival
    Time Frame:Up to 6 months
    Safety Issue:
    Description:Stratified log-rank test will be used to compare cancer-free survival between treatment groups. The Cox (proportional hazards) regression model will be used to incorporate potential prognostic factors and treatment assignments as covariates.
    Measure:Overall survival
    Time Frame:Up to 6 months
    Safety Issue:
    Description:
    Measure:Incidence of adverse events
    Time Frame:Up to 6 months
    Safety Issue:
    Description:A Bayesian method to monitor the toxicity in the perioperative phase will be used. Toxicity data will be summarized by frequency tables.
    Measure:Quality of life survival determined by phone calls during follow up
    Time Frame:Up to 6 months
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:M.D. Anderson Cancer Center

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