Clinical Trials /

Pembrolizumab Every 12 Weeks Versus Every 3 Weeks in Treating Patients With Non-small Cell Lung Cancer

NCT04032418

Description:

This phase II trial studies how well pembrolizumab given every 12 weeks works compared to every 3 weeks in treating patients with non-small cell lung cancer. 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. Giving pembrolizumab every 12 weeks may provide similar disease control with fewer treatments for patients with non-small cell lung cancer when compared to every 3 weeks. Demonstrating that 12 week dosing is as effective as 3 week dosing may also have a significant impact when considering the cost required for these medications.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab Every 12 Weeks Versus Every 3 Weeks in Treating Patients With Non-small Cell Lung Cancer
  • Official Title: Randomized Phase II Study of Pembrolizumab Q 12 Weeks Versus Q 3 Weeks in NSCLC With Clinical Benefit to Pembrolizumab Monotherapy: Multicenter International Study

Clinical Trial IDs

  • ORG STUDY ID: i 82319
  • SECONDARY ID: NCI-2019-04326
  • SECONDARY ID: i 82319
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT04032418

Conditions

  • Lung Non-Small Cell Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Arm I (pembrolizumab 3 weeks)

Purpose

This phase II trial studies how well pembrolizumab given every 12 weeks works compared to every 3 weeks in treating patients with non-small cell lung cancer. 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. Giving pembrolizumab every 12 weeks may provide similar disease control with fewer treatments for patients with non-small cell lung cancer when compared to every 3 weeks. Demonstrating that 12 week dosing is as effective as 3 week dosing may also have a significant impact when considering the cost required for these medications.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the 1-year progression-free survival rate with pembrolizumab administered
      every 3 weeks compared to pembrolizumab administered every 12 weeks.

      SECONDARY OBJECTIVES:

      I. To assess overall survival between the two treatment groups. II. To assess the serious
      adverse event profiles between the two treatment groups.

      EXPLORATORY OBJECTIVES:

      I. To evaluate circulating biomarkers of treatment response and resistance. II. To
      characterize fecal microbiotic profile and to correlate those results with tumor
      characteristics and antitumor immune responses.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive pembrolizumab intravenously (IV) over 30 minutes every 3 weeks for up
      to 24 months in the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive pembrolizumab IV over 30 minutes every 12 weeks for up to 24 months
      in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, and then every 12
      weeks for at least 12 months.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (pembrolizumab 3 weeks)Active ComparatorPatients receive pembrolizumab IV over 30 minutes every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab
Arm II (pembrolizumab 12 weeks)ExperimentalPatients receive pembrolizumab IV over 30 minutes every 12 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at the
             time of study treatment initiation.

          -  Have pathologically confirmed diagnosis of non-small cell lung cancer (NSCLC). Mixed
             small cell lung cancer (SCLC) histology is not allowed.

          -  Must be eligible for treatment with pembrolizumab as standard of care (up to third
             line).

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L.

          -  Platelets >= 100 x 10^9/L.

          -  Hemoglobin >= 9 g/dL.

          -  Plasma creatinine =< 1.5 x institution upper limit of normal (ULN) or estimated
             glomerular filtration rate (GFR) (measured or calculated with Cockcroft and Gault
             formula) > 45 ml/min.

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (ALT
             and AST =< 5 x ULN is acceptable if liver metastases are present).

          -  Total plasma bilirubin =< 1.5 x ULN. For patients with well documented Gilbert?s
             syndrome, total bilirubin =< 3 x ULN with direct bilirubin within normal range.

          -  Must have demonstrated complete response, partial response by Response Evaluation
             Criteria in Solid Tumors (RECIST) or stable disease if > 5% but less than 30% decrease
             from baseline total tumor burden (target lesions) to pembrolizumab at the time of
             randomization for study treatment.

          -  Must have received at least 6 months of pembrolizumab treatment (but no more than 15
             months) prior to start of protocol-assigned treatment.

          -  Participants of child-bearing potential must agree to use adequate contraceptive
             methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
             entry. Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately.

          -  Participant or legal representative must understand the investigational nature of this
             study and sign an Independent Ethics Committee/Institutional Review Board approved
             written informed consent form prior to receiving any study related procedure.

        Exclusion Criteria:

          -  Receipt of anticancer chemotherapy, other than pembrolizumab, within 6 months prior to
             randomization.

          -  Disease progression to pembrolizumab as assessed by immune related (ir)RECIST.

          -  Prior radiotherapy or gamma knife within 2 weeks of study treatment for non-brain
             metastasis. Subjects must have recovered from all radiation related toxicities.

          -  Active/untreated brain metastasis. Whole brain radiation or gamma knife radiosurgery
             performed less than 4 weeks prior to first administration of study drug. Previously
             treated brain metastasis allowed as long as not requiring steroids and stable on
             imaging at least 4 weeks after completing radiation therapy.

          -  Leptomeningeal involvement regardless of tumor response status.

          -  Tumor with mutation that is known to be sensitive to Food and Drug Administration
             (FDA)- approved targeted therapy.

          -  Patients who had pembrolizumab interrupted for more than 4 weeks for management of
             treatment-related adverse event.

          -  Currently receiving or has received high-dose systemic corticosteroids within 4 weeks
             prior to starting study drug for management of brain metastases, or who have not fully
             recovered from side effects of such treatment. Patients who are on low-dose prednisone
             (10 mg once daily or less) for at least 6 months for the management of other chronic
             disorders (e.g. chronic obstructive pulmonary disease [COPD]) is allowed. Steroids for
             endocrine replacement or receipt of short-course of steroids during the preceding 4
             week period as supportive medication such as for drug allergy, anti-emetic, etc. is
             allowed.

          -  Had major surgery within 14 days prior to starting protocol treatment.

          -  Active, clinically serious infections or other serious uncontrolled medical
             conditions.

          -  Pregnant or nursing female participants.

          -  Any condition which in the investigator?s opinion deems the participant an unsuitable
             candidate to receive study drug.

          -  Unwilling or unable to follow protocol requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:1-year progression-free survival (PFS)
Time Frame:Baseline to 12 months
Safety Issue:
Description:Measured using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 12 months after treatment completion
Safety Issue:
Description:Defined as the number of months between Loading Phase enrollment and death from any cause. Analysis of overall survival between the two treatment groups will be carried forth using a log-rank test accounting for the stratification factors, including other known variables such as PD-L1 tumor proportion score, line of therapy, histology, mutation profile.
Measure:Incidence of adverse events
Time Frame:Up to 12 months
Safety Issue:
Description:Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Will be assessed through the evaluation of grade 3 or higher toxicities deemed possibly related to treatment. Both efficacy and toxicity rates will be estimated using simple relative frequencies. The corresponding 95% confidence intervals for the estimated probabilities will be computed.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Roswell Park Cancer Institute

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