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

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ClinicalTrials.gov Identifier: NCT04032418
Recruitment Status : Recruiting
First Posted : July 25, 2019
Last Update Posted : February 21, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE July 18, 2019
First Posted Date  ICMJE July 25, 2019
Last Update Posted Date February 21, 2021
Actual Study Start Date  ICMJE February 13, 2020
Estimated Primary Completion Date September 3, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
1-year progression-free survival (PFS) [ Time Frame: Baseline to 12 months ]
Measured using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • Overall survival [ Time Frame: Up to 12 months after treatment completion ]
    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.
  • Incidence of adverse events [ Time Frame: Up to 12 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 30, 2019)
  • Cox regression models in terms of treatment resistance [ Time Frame: Up to 12 months ]
    Circulating biomarkers of treatment response and resistance
  • Length of time on treatment [ Time Frame: Up to 12 months ]
    Length of time on treatment as a time varying covariate will be carried out using Cox regression models.
Original Other Pre-specified Outcome Measures
 (submitted: July 19, 2019)
  • Circulating biomarkers of treatment response and resistance [ Time Frame: Up to 12 months ]
    Will be carried out using Cox regression models for continuous biomarkers and logistic regression in terms of treatment resistance.
  • Length of time on treatment [ Time Frame: Up to 12 months ]
    Length of time on treatment as a time varying covariate will be carried out using Cox regression models.
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab Every 12 Weeks Versus Every 3 Weeks in Treating Patients With Non-small Cell Lung Cancer
Official Title  ICMJE Randomized Phase II Study of Pembrolizumab 200mg every12 Weeks Versus Every 3 Weeks in NSCLC With Clinical Benefit to Pembrolizumab Monotherapy: Multicenter International Study
Brief Summary 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 200mg pembrolizumab administered every 3 weeks compared to 200mg 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Non-Small Cell Carcinoma
Intervention  ICMJE Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475
Study Arms  ICMJE
  • Active Comparator: Arm I (200mg pembrolizumab 3 weeks)
    Patients receive 200mg pembrolizumab IV over 30 minutes every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
    Intervention: Biological: Pembrolizumab
  • Experimental: Arm II (200mg pembrolizumab 12 weeks)
    Patients receive 200mg pembrolizumab IV over 30 minutes every 12 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
    Intervention: Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 19, 2019)
152
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 3, 2023
Estimated Primary Completion Date September 3, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.Patients with new brain metastasis isolated in the brain while on pembrolizumab monotherapy will be eligible as long as extracranial disease control fulfills the criteria otherwise (i.e. this will not be considered as disease progression for the purpose of this study).
  • Must have received at least 6 months of pembrolizumab monotherapy treatment (but no more than 15 months total duration, including treatment in combination with chemotherapy prior to maintenance phase) 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04032418
Other Study ID Numbers  ICMJE i 82319
NCI-2019-04326 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
i 82319 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Grace K Dy Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP