- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04032418
Pembrolizumab Every 12 Weeks Versus Every 3 Weeks in Treating Patients With Non-small Cell Lung Cancer
Randomized Phase II Study of Pembrolizumab 200mg every12 Weeks Versus Every 3 Weeks in NSCLC With Clinical Benefit to Pembrolizumab Monotherapy: Multicenter International Study
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
-
Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Given IV
Other Names:
|
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.
|
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
1-year progression-free survival (PFS)
Time Frame: Baseline to 12 months
|
Measured using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
|
Baseline to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 12 months after treatment completion
|
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.
|
Up to 12 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cox regression models in terms of treatment resistance
Time Frame: Up to 12 months
|
Circulating biomarkers of treatment response and resistance
|
Up to 12 months
|
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.
|
Up to 12 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Grace K Dy, Roswell Park Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- i 82319 (Other Identifier: Roswell Park Cancer Institute)
- NCI-2019-04326 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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