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EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer

Primary Purpose

Colo-rectal Cancer

Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Leucovorin
Oxaliplatin
Fluorouracil
Bevacizumab
Irinotecan
Cetuximab
Metastasectomy
Biospecimen collection
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colo-rectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum that cannot be removed by surgery without prior systemic therapy for advanced disease (prior adjuvant chemotherapy completed >12 months from diagnosis of metastatic or advanced disease is allowed) for cohorts A and C and with one prior line of therapy but no more than 2 prior lines of therapy for advanced disease (prior adjuvant chemotherapy completed <12 months from diagnosis of metastatic or advanced disease is considered one line of therapy). Cohort A: May have received 1 cycle of mFOLFOX6± Bevacizumab pending results of RAS and BRAF. If results determine patient is eligible, the patient will be enrolled and will received the addition of CIMAvax + Bevacizumab in their second cycle. Cohort B: Patients with RAS- and BRAF wild-type metastatic CRC who have received at least one but no more than 2 prior therapies for advanced disease Cohort C: Patients with RAS- and BRAF wild-type metastatic CRC who have not received prior therapy for advanced disease and are candidates for liver metastasectomy (one cycle of standard therapy with mFOLFOX6 with or without appropriate biologic agent is allowed) KRAS/NRAS/BRAF (V600) wild-type. Have an ECOG Performance Status of 0 1. Refer to Appendix A. Patients must have adequate organ and marrow function as defined below: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 8 g/dL Creatinine clearance> 60 mL/min (Cockcroft-Gault Equation) ALT and AST ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present Total bilirubin ≤ 1.5x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3x ULN with direct bilirubin within normal range Have measurable disease per RECIST 1.1 criteria present. 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 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. Participant agrees to provide tumor biopsy tissue while on study (cohort A and B) or allow tissue to be taken during surgery (cohort C) Exclusion Criteria: Toxicity ≥Grade 2 from prior chemotherapy. Other cancer requiring active treatment. Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for colorectal cancer treatment. Had major surgery within 4 weeks 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. HIV, AIDS or other immune depressing disease). Testing is not mandatory. Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Active, clinically serious infections or other serious uncontrolled medical conditions or psychiatric illness/social situations that would limit compliance with study requirements. 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 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) within 6 months prior to baseline Uncontrolled hypertension (SBP>160/DBP>100 despite medical intervention). History of myocarditis of any etiology History of ventricular arrhythmias Active major or clinically significant bleeding based on the International Society on Thrombosis and Hemostasis definition. Pregnant or nursing female participants.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Cohort A

    Cohort B1

    Cohort B2

    Cohort C

    Arm Description

    LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy consisting of leucovorin IV, oxaliplatin IV over 2 hours, and fluorouracil IV and bevacizumab IV over 10 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.

    LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive FOLFIRI consisting of irinotecan IV, leucovorin IV over 90 minutes, and fluorouracil IV and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.

    LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial

    Description LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 and cetuximab, FOLFOX6 and bevacizumab, or mFOLFOX6 per investigators preference. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo metastasectomy 4-8 weeks after first maintenance phase dose. Patients undergo collection of blood samples throughout the trial.

    Outcomes

    Primary Outcome Measures

    Immunogencity of vaccine
    Percentage of patients with antibody titers greater than or equal to 1:4000 using a 90% confidence interval obtained by Jeffery's prior method

    Secondary Outcome Measures

    Progression free survival

    Full Information

    First Posted
    August 21, 2023
    Last Updated
    October 23, 2023
    Sponsor
    Roswell Park Cancer Institute
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06011772
    Brief Title
    EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer
    Official Title
    A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 2, 2023 (Anticipated)
    Primary Completion Date
    November 2, 2025 (Anticipated)
    Study Completion Date
    November 2, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Roswell Park Cancer Institute

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to determine the immunogenicity of the CIMAvaxEGF® vaccine (that is, its effectiveness in inducing an anti-tumor immune response) in patients with metastatic KRAS/NRAS/BRAF wild-type gene colorectal cancer, when given in combination with standard therapies used in the treatment of advanced colorectal cancer.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colo-rectal Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    42 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Cohort A
    Arm Type
    Experimental
    Arm Description
    LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy consisting of leucovorin IV, oxaliplatin IV over 2 hours, and fluorouracil IV and bevacizumab IV over 10 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.
    Arm Title
    Cohort B1
    Arm Type
    Experimental
    Arm Description
    LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive FOLFIRI consisting of irinotecan IV, leucovorin IV over 90 minutes, and fluorouracil IV and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.
    Arm Title
    Cohort B2
    Arm Type
    Experimental
    Arm Description
    LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial
    Arm Title
    Cohort C
    Arm Type
    Experimental
    Arm Description
    Description LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 and cetuximab, FOLFOX6 and bevacizumab, or mFOLFOX6 per investigators preference. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo metastasectomy 4-8 weeks after first maintenance phase dose. Patients undergo collection of blood samples throughout the trial.
    Intervention Type
    Biological
    Intervention Name(s)
    Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
    Other Intervention Name(s)
    Cimavax, CIMAvax EGF, Epidermal Growth Factor (EGF) Vaccine
    Intervention Description
    Given IM
    Intervention Type
    Drug
    Intervention Name(s)
    Leucovorin
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    Oxaliplatin
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    Fluorouracil
    Intervention Description
    Given IV
    Intervention Type
    Biological
    Intervention Name(s)
    Bevacizumab
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    Irinotecan
    Intervention Description
    Given IV
    Intervention Type
    Biological
    Intervention Name(s)
    Cetuximab
    Intervention Description
    Given IV
    Intervention Type
    Procedure
    Intervention Name(s)
    Metastasectomy
    Intervention Description
    Undergo metastasectomy
    Intervention Type
    Procedure
    Intervention Name(s)
    Biospecimen collection
    Intervention Description
    Undergo collection of blood samples
    Primary Outcome Measure Information:
    Title
    Immunogencity of vaccine
    Description
    Percentage of patients with antibody titers greater than or equal to 1:4000 using a 90% confidence interval obtained by Jeffery's prior method
    Time Frame
    up to 60 days after last dose
    Secondary Outcome Measure Information:
    Title
    Progression free survival
    Time Frame
    time from treatment until disease progression, death or last follow up assesed up to 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum that cannot be removed by surgery without prior systemic therapy for advanced disease (prior adjuvant chemotherapy completed >12 months from diagnosis of metastatic or advanced disease is allowed) for cohorts A and C and with one prior line of therapy but no more than 2 prior lines of therapy for advanced disease (prior adjuvant chemotherapy completed <12 months from diagnosis of metastatic or advanced disease is considered one line of therapy). Cohort A: May have received 1 cycle of mFOLFOX6± Bevacizumab pending results of RAS and BRAF. If results determine patient is eligible, the patient will be enrolled and will received the addition of CIMAvax + Bevacizumab in their second cycle. Cohort B: Patients with RAS- and BRAF wild-type metastatic CRC who have received at least one but no more than 2 prior therapies for advanced disease Cohort C: Patients with RAS- and BRAF wild-type metastatic CRC who have not received prior therapy for advanced disease and are candidates for liver metastasectomy (one cycle of standard therapy with mFOLFOX6 with or without appropriate biologic agent is allowed) KRAS/NRAS/BRAF (V600) wild-type. Have an ECOG Performance Status of 0 1. Refer to Appendix A. Patients must have adequate organ and marrow function as defined below: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 8 g/dL Creatinine clearance> 60 mL/min (Cockcroft-Gault Equation) ALT and AST ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present Total bilirubin ≤ 1.5x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3x ULN with direct bilirubin within normal range Have measurable disease per RECIST 1.1 criteria present. 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 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. Participant agrees to provide tumor biopsy tissue while on study (cohort A and B) or allow tissue to be taken during surgery (cohort C) Exclusion Criteria: Toxicity ≥Grade 2 from prior chemotherapy. Other cancer requiring active treatment. Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for colorectal cancer treatment. Had major surgery within 4 weeks 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. HIV, AIDS or other immune depressing disease). Testing is not mandatory. Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Active, clinically serious infections or other serious uncontrolled medical conditions or psychiatric illness/social situations that would limit compliance with study requirements. 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 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) within 6 months prior to baseline Uncontrolled hypertension (SBP>160/DBP>100 despite medical intervention). History of myocarditis of any etiology History of ventricular arrhythmias Active major or clinically significant bleeding based on the International Society on Thrombosis and Hemostasis definition. Pregnant or nursing female participants.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Deepak Vadehra
    Phone
    716-845-2300
    Email
    askroswell@roswellpark.org
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Deepak Vadehra
    Organizational Affiliation
    Roswell Park Comprehensive Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer

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