Lung Cancer Clinical Trial
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
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.
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.
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.
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
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
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There is 1 Location for this study
Winston-Salem North Carolina, 27157, United States
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