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CIMAvax Vaccine and Nivolumab in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer

This study is currently recruiting participants.
Verified July 2017 by Roswell Park Cancer Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT02955290
First Posted: November 4, 2016
Last Update Posted: July 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute
November 2, 2016
November 4, 2016
July 11, 2017
December 9, 2016
June 9, 2020   (Final data collection date for primary outcome measure)
  • DLT as graded by CTCAE v. 4.03 (Phase I) [ Time Frame: Up to 4 weeks (2 doses of study drugs) ]
    No formal analyses of DLTs are planned. Presentation of DLTs will be limited to DLT-evaluable patients.
  • Overall survival (Phase II) [ Time Frame: At 12 months ]
    Overall survival will be presented using Kaplan-Meier plots and associated statistics.
  • Percentage of patients with high antibody titers defined as >= 1:4000 (Phase I) [ Time Frame: At 12 months ]
    The percentage of patients with antibody titers >= 1:4000 at 12 months will be presented by treatment schedule and by time point (0, 3, 6, 9, and 12 months). In addition, a mixed effects model will be used to analyze and compare treatment schedules across time. Antibody titers may be transformed (e.g., log) as appropriate.
  • DLT as graded by CTCAE v. 4.03 (Phase I) [ Time Frame: Up to 4 weeks (2 doses of study drugs) ]
    No formal analyses of DLTs are planned. Presentation of DLTs will be limited to DLT-evaluable patients.
  • Overall survival (Phase II) [ Time Frame: At 12 months ]
    Overall survival will be presented using Kaplan-Meier plots and associated statistics.
  • Percentage of patients with high antibody titers defined as >= 1:4000 (Phase I) [ Time Frame: Up to 12 months from 5th vaccine dose ]
    The percentage of patients with antibody titers >= 1:4000 at 12 months will be presented by treatment schedule and by time point (0, 3, 6, 9, and 12 months). In addition, a mixed effects model will be used to analyze and compare treatment schedules across time. Antibody titers may be transformed (e.g., log) as appropriate.
Complete list of historical versions of study NCT02955290 on ClinicalTrials.gov Archive Site
  • Incidence of adverse events (AEs) graded according to NCI CTCAE v4.03 (Phase I and II) [ Time Frame: Up to 30 days after the last dose of study treatment ]
    The maximum grade for each type of AEs will be recorded for each patient based on NCI CTCAE version 4.0. The frequency of AEs will be tabulated by maximum grade per event across all dose levels and cycles. All patients who receive any study treatment will be considered evaluable for toxicity.
  • PFS based on irRECIST (Phase II) [ Time Frame: Up to 12 months ]
    PFS will be presented using Kaplan-Meier plots and associated statistics.
  • EGFR and PD-1 expression and mutations in tumor tissue (Phase I and II) [ Time Frame: Up to 14 days after the last dose of CIMAvax ]
    EGFR and PD-1 expression and mutations in tumor tissue will be reported using appropriate descriptive statistics. The association between these measures and the biomarkers of immune response will be evaluated using general linear models.
  • Incidence of adverse events (AEs) graded according to NCI CTCAE v4.03 (Phase I and II) [ Time Frame: Up to 30 days after the last dose of study treatment ]
    The maximum grade for each type of AEs will be recorded for each patient based on NCI CTCAE version 4.0. The frequency of AEs will be tabulated by maximum grade per event across all dose levels and cycles. All patients who receive any study treatment will be considered evaluable for toxicity.
  • PFS based on irRECIST (Phase II) [ Time Frame: Up to 12 months ]
    PFS will be presented using Kaplan-Meier plots and associated statistics.
  • Serum EGF levels, platelet levels, markers of immune response, and antibody functionality (Phase I and II) [ Time Frame: Up to 12 months from 5th vaccine dose ]
    Serum EGF levels, platelet levels, and biomarkers of immune response will be reported using appropriate descriptive statistics. Associations between these measures will be explored in the overall sample using the correlation coefficients.
  • Blood EGF levels, platelet levels, markers of immune response, and antibody functionality (Phase I and II) [ Time Frame: Up to 12 months from 5th vaccine dose ]
    Blood EGF levels, platelet levels, and biomarkers of immune response will be reported using appropriate descriptive statistics. Associations between these measures will be explored in the overall sample using the correlation coefficients.
  • EGFR and PD-1 expression and mutations in tumor tissue (Phase I and II) [ Time Frame: Up to 14 days after the last dose of CIMAvax ]
    EGFR and PD-1 expression and mutations in tumor tissue will be reported using appropriate descriptive statistics. The association between these measures and the biomarkers of immune response will be evaluated using general linear models.
  • Response assessed using irRECIST, irRC, and RECIST 1.1 (Phase I and II) [ Time Frame: Up to 12 months ]
    Response assessment criteria will be compared between irRECIST, irRC, and RECIST 1.1 for a prospective analysis.
Not Provided
 
CIMAvax Vaccine and Nivolumab in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer
A Phase I/II Study of the EGF Vaccine CIMAvax in Combination With the Anti-PD1 Nivolumab in Patients With Previously Treated Advanced NSCLC
This partially randomized phase I/II trial studies the best dose and side effects of recombinant human EGF-rP64K/montanide ISA 51 vaccine (CIMAvax) and nivolumab and to see how well they work in treating patients with stage III-IV non-small cell lung cancer. Vaccine therapy, such as CIMAvax vaccine may help slow down and stop tumor growth. Monoclonal antibodies, such as nivolumab, may block a protein needed by tumor cells to grow and spread. Giving CIMAvax vaccine together with nivolumab may work better in treating patients with stage IIIB-IV non-small cell lung cancer.

PRIMARY OBJECTIVES:

I. To identify the maximum dose of CIMAvax in combination with nivolumab based on dose limiting toxicities (DLTs) as assessed by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). (Phase I) II. To examine the effect of the dose and the dosing intervals (starting in the expansion phase of the maximum tolerated dose) on antibody titers when CIMAvax is combined with nivolumab in the second-line therapy of advanced non-small cell lung cancer (NSCLC). (Phase I) III. To evaluate the 12-month overall survival of CIMAvax combined with nivolumab in patients with advanced NSCLC. (Phase II)

SECONDARY OBJECTIVES I. To assess the toxicity of CIMAvax combined with nivolumab using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). (Phase I) II. Determine the preliminary efficacy of the study combination utilizing immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) guidelines. (Phase I) III. To evaluate progression free survival (PFS) for the combination of CIMAvax and nivolumab in patients with advanced NSCLC. (Phase II) IV. To assess the toxicity of CIMAvax combined with nivolumab using the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.03). (Phase II)

TERTIARY OBJECTIVES:

I. To conduct correlative studies comparing blood EGF levels, platelet levels, markers of immune response and functionality of antibody response. (Phase I) II. To examine the association of EGFR (total and activated), PD-1 and PD-L1 expression and mutations in tumor tissue with biomarkers of genetic and immune response. (Phase I and II) III. Comparison of response assessment criteria for a prospective analysis (irRECIST response assessment versus [vs.] immune-related Response Criteria [irRC] vs. RECIST 1.1). (Phase I and II) IV. To characterize the blood EGF levels and other blood-based biomarkers of patients censored from the trial because of low titer response. (Phase II)

OUTLINE: This is a phase I dose escalation study of CIMAvax followed by a phase II study.

PHASE I: Patients receive CIMAvax intramuscularly (IM) and nivolumab intravenously (IV) over 60 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Within 4 weeks after the 4th dose, patients receive CIMAvax IM at the same time as the next nivolumab dose.

MAINTENANCE PHASE I: Patients with antibody titer < 1:4000 and who do not experience a DLT receive CIMAvax every 4 weeks and nivolumab every 2 weeks. Patients with antibody titer >= 1:4000 and who do not experience a DLT are randomized to 1 of 3 groups.

GROUP A: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Courses repeat every 4 weeks for CIMAvax and every 2 weeks for nivolumab in the absence of disease progression or unacceptable toxicity.

GROUP B: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Courses repeat every 8 weeks for CIMAvax and every 2 weeks for nivolumab in the absence of disease progression or unacceptable toxicity.

GROUP C: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Courses repeat every 12 weeks for CIMAvax and every 2 weeks for nivolumab in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 30 days for 120 days.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • ALK Gene Mutation
  • EGFR Gene Mutation
  • Recurrent Non-Small Cell Lung Carcinoma
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Nivolumab
    Given IV
    Other Names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
  • Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
    Given CIMAvax IM
    Other Names:
    • Center of Molecular Immunology (CIMA) Epidermal Growth Factor (EGF) Vaccine
    • Center of Molecular Immunology Epidermal Growth Factor Vaccine
    • CimaVax
    • CIMAvax EGF
    • CIMAvax Epidermal Growth Factor Vaccine
    • CIMAvax-EGF
    • Recombinant Human EGF-P64K/Montanide Vaccine
  • Experimental: Group A (CIMAvax, nivolumab)

    PHASE I: Patients receive CIMAvax IM and nivolumab IV over 60 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Within 4 weeks after the 4th dose, patients receive CIMAvax IM at the same time as the next nivolumab dose.

    MAINTENANCE PHASE I: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Courses repeat every 4 weeks for CIMAvax and every 2 weeks for nivolumab in the absence of disease progression or unacceptable toxicity.

    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Biological: Nivolumab
    • Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
  • Experimental: Group B (CIMAvax, nivolumab)

    PHASE I: Patients receive CIMAvax IM and nivolumab IV over 60 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Within 4 weeks after the 4th dose, patients receive CIMAvax IM at the same time as the next nivolumab dose.

    MAINTENANCE PHASE I: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Courses repeat every 8 weeks for CIMAvax and every 2 weeks for nivolumab in the absence of disease progression or unacceptable toxicity.

    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Biological: Nivolumab
    • Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
  • Experimental: Group C (CIMAvax, nivolumab)

    PHASE I: Patients receive CIMAvax IM and nivolumab IV over 60 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Within 4 weeks after the 4th dose, patients receive CIMAvax IM at the same time as the next nivolumab dose.

    MAINTENANCE PHASE I: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Courses repeat every 12 weeks for CIMAvax and every 2 weeks for nivolumab in the absence of disease progression or unacceptable toxicity.

    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Biological: Nivolumab
    • Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
136
June 9, 2021
June 9, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Have pathologically confirmed diagnosis of advanced NSCLC (stage IIIB or stage IV, as defined by the American Joint Committee on Cancer staging system-TNM 7th edition, 2010)
  • Must be eligible for treatment with nivolumab as standard of care
  • Patients with advanced (metastatic) NSCLC, whose disease progressed during or after platinum-based chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on Food and Drug Administration (FDA)- approved therapy for these aberrations prior to receiving nivolumab
  • Have at least 6 month life expectancy
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dL
  • Serum creatinine =< 1.5 x institution upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (ALT and AST =< 5 x ULN is acceptable if liver metastases are present)
  • Total serum bilirubin =< 1.5 x ULN; for patients with well documented Gilbert's syndrome, total bilirubin =< 3 x ULN with direct bilirubin within normal range
  • Troponin-I, creatine kinase muscle and brain (CK-MB), B-type natriuretic peptide (BNP) =< ULN
  • Left ventricular ejection fraction (LVEF) >= LLN (institutional limit)
  • Phase II only: blood EGF level >= pg/mL at baseline (to be determined based on Phase I results)
  • 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
  • Phase II only: participant agrees to provide tumor biopsy tissue before treatment, blood samples at the start of treatment and at multiple times during the study and, a tumor biopsy at the end of the trial or after disease progression

Exclusion Criteria:

  • Receipt of anticancer chemotherapy within 4 weeks before the administration of study drug
  • Previous immunotherapy or investigational agents within 6 months of first administration of study drug
  • Any patients requiring oxygen therapy
  • Prior radiotherapy or gamma knife within 2 weeks of study treatment; 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 treatment status
  • Tumor with mutation that is known to be sensitive to FDA approved targeted therapy but has not yet received such targeted therapy
  • History of autoimmune disorder, with exception of patients with vitiligo or endocrine- related autoimmune conditions receiving appropriate hormonal supplementation who are eligible; use of immunosuppressant drugs such as steroids (except as hormone replacement therapy), azathioprine, tacrolimus, cyclosporine, etc.; use is not permitted within 4 weeks before recruitment
  • Currently receiving or has received systemic corticosteroids within 4 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment (steroids for endocrine replacement is allowed)
  • Had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery
  • Has known immunosuppressive disease (e.g. human immunodeficiency virus [HIV], acquired immune deficiency syndrome [AIDS] or other immune depressing disease); testing is not mandatory
  • Active, clinically serious infections or other serious uncontrolled medical conditions
  • Patient has known hypersensitivity to the components of the study drugs or any analogs
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator, including, but not limited to:

    • Myocardial infarction or arterial or venous thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) class III or IV disease
    • History of documented congestive heart failure (New York Heart Association functional classification III or IV)
    • Documented history of cardiomyopathy.
    • Uncontrolled hypertension (systolic blood pressure [SBP] > 160/diastolic blood pressure [DBP] > 100 despite medical intervention)
    • History of myocarditis of any etiology
    • History of cardiac surgery
    • History of ventricular arrhythmias
  • Patients diagnosed with an invasive cancer within 2 years prior to starting protocol therapy with the following exceptions: non-melanoma skin cancers, in-situ cancers, and prostate cancer Gleason =< to 6 (under surveillance or treated)
  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
United States
 
 
NCT02955290
I 286816
NCI-2016-01467 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 286816 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Roswell Park Cancer Institute
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Grace Dy Roswell Park Cancer Institute
Roswell Park Cancer Institute
July 2017

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