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

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ClinicalTrials.gov Identifier: NCT02955290
Recruitment Status : Recruiting
First Posted : November 4, 2016
Last Update Posted : May 4, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Biological: Nivolumab Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of the EGF Vaccine CIMAvax in Combination With the Anti-PD1 Nivolumab in Patients With Previously Treated Advanced NSCLC
Study Start Date : December 9, 2016
Estimated Primary Completion Date : June 9, 2020
Estimated Study Completion Date : June 9, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
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.

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 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.

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 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.

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




Primary Outcome Measures :
  1. 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.

  2. Overall survival (Phase II) [ Time Frame: At 12 months ]
    Overall survival will be presented using Kaplan-Meier plots and associated statistics.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. PFS based on irRECIST (Phase II) [ Time Frame: Up to 12 months ]
    PFS will be presented using Kaplan-Meier plots and associated statistics.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 systemic steroids (except as hormone replacement therapy or short-course supportive medication such as chemotherapy or drug allergy, etc.), azathioprine, tacrolimus, cyclosporine, etc.; Systemic use is not permitted within 4 weeks before recruitment
  • Currently receiving or has received 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 (steroids for endocrine replacement or receipt of short-course of steroids during this 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02955290


Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    ASKRPCI@RoswellPark.org   
Principal Investigator: Grace K. Dy         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Grace Dy Roswell Park Cancer Institute

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT02955290     History of Changes
Other Study ID Numbers: 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 )
First Posted: November 4, 2016    Key Record Dates
Last Update Posted: May 4, 2018
Last Verified: May 2018

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Vaccines
Antibodies, Monoclonal
Nivolumab
Mitogens
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action