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

NCT02581943 | Completed Phase 2 Results FDA Drug

• 5 other identifiers: IRB00034830NCI-2015-01708CCCWFU #62415CCCWFU 62415P30CA012197
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Non-Small Cell Lung Carcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Duration of Response

  Duration of response will also be assessed in each group and compared using survival analysis methods. Per response evaluation criteria in Solid Tumors Criteria: Complete Response (irCR): Complete disappearance of all target and new, measurable lesions, with the exceptions of lymph nodes which must decrease to \< 10 mm in short axis; Partial Response (irPR): Decrease in TMTB ≥ 30% relative to baseline; Stable Disease (irSD): Not meeting criteria for irCR or irPR, in absence of irPD; Progressive Disease (irPD): Increase in TMTB ≥ 20% relative to nadir.

  Up to 2 years

• Change in Effect of Treatment in Immune Markers From Baseline to End of Treatment (up to 2 Years)

  Immune markers were measured at baseline and post-treatment. Data reported are the difference (post-pre) in these immune markers. Wilcoxon rank-sum tests were used to analyze the effects of the treatments on the change in immune markers.

  Baseline and end of treatment (up to 2 years)

• Objective Response Rate (ORR), Assessed Using RECIST

  The Fisher's exact test methods will be used to estimate ORR between groups. The Exact Clopper-Pearson 95% confidence intervals will be calculated for each group. Per response evaluation criteria in Solid Tumors Criteria: Complete Response (irCR): Complete disappearance of all target and new, measurable lesions, with the exceptions of lymph nodes which must decrease to \< 10 mm in short axis; Partial Response (irPR): Decrease in TMTB ≥ 30% relative to baseline; Stable Disease (irSD): Not meeting criteria for irCR or irPR, in absence of irPD; Progressive Disease (irPD): Increase in TMTB ≥ 20% relative to nadir.

  Up to 2 years

• Overall Survival

  The Kaplan Meier curves will be used to estimate overall survival rates.

  Duration of time from randomization to the time of death due to any cause, or the date the subject was last confirmed to be alive, assessed up to 3 years

• Progression Free Survival

  The Kaplan Meier curves will be used to estimate progression free survival rates. Per response evaluation criteria in Solid Tumors Criteria: Progressive Disease (irPD): Increase in TMTB ≥ 20% relative to nadir.

  Duration of time from randomization to the time of immune-related progressive disease or death, whichever comes first, assessed up to 3 years

Secondary Outcomes (2)

• Number of Participants With Reported Adverse Events - CTCAE Version 4.0

  At baseline, at week 8, week 12, week 20 and up to 30 days after last study drug is administered

• Change in Immune Markers From Baseline to End of Treatment (up to 2 Years) With Treatment Response

  At baseline and post-treatment

Study Arms (2)

Arm I (pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Quality-of-Life Assessment

Arm II (pembrolizumab, paclitaxel, carboplatin)

EXPERIMENTAL

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. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Biological: Pembrolizumab; Other: Quality-of-Life Assessment

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm II (pembrolizumab, paclitaxel, carboplatin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (pembrolizumab); Arm II (pembrolizumab, paclitaxel, carboplatin)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm II (pembrolizumab, paclitaxel, carboplatin)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm I (pembrolizumab); Arm II (pembrolizumab, paclitaxel, carboplatin)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (pembrolizumab); Arm II (pembrolizumab, paclitaxel, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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). Patients with epidermal growth factor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangement or ROS1 translocation must have received an approved EGFR, ALK, or ROS1-directed therapy and have signs of disease progression prior to receiving pembrolizumab.
• Patients must 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 12 weeks (84 days) prior to date of signing consent.
• Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen (up to 3 years) only upon agreement from the Sponsor. At least 4 mm of tumor tissue will be needed for PD-L1 staining.
• Patients who have received zero (0) to two (2) previous lines of systemic chemotherapy and are not currently receiving chemotherapy treatment (within 2 weeks of randomization).
• At least one measurable lesion as defined by RECIST v1.1 on screening computed tomography (CT) or magnetic resonance imaging (MRI)
• Age \>18 years.
• ECOG performance status of 2.
• Patients must have normal organ and marrow function as defined below:
• white blood cell count \> 2,500 cells/mcL
• absolute neutrophil count \>1,500/mcL
• platelets \>100,000/mcL
• hemoglobin ≥ 9 g/dL
• total bilirubin ≤ 2.0 x upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) \< 2.5 x ULN Or ≤ 5 x ULN in presence of liver metastases
• creatinine within normal institutional limits OR

You may not qualify if:

• 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 2 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 total doses of corticosteroids equivalent to 10 mg of prednisone or less.
• 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 PD1/PD-L1 agent
• Patients receiving any other investigational agents and or more than 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 HIV infection, Hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or at risk for HBV reactivation. HBV DNA and testing for HCV RNA must be undetectable. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; Paclitaxel; Taxes; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Assistant Director of Clinical Research Operations
• Organization: Wake Forest Baptist Comprehensive Cancer Center

mebrown@wakehealth.edu

336-713-6913

Study Officials

• William J Petty, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 21, 2015
• Study Start: June 17, 2016
• Primary Completion: November 19, 2022
• Study Completion: December 28, 2022
• Last Updated: January 5, 2024
• Results First Posted: January 5, 2024

Record last verified: 2023-12

Locations

US (1)