Clinical Trials /

Study of Imprime PGG® in Combination With Cetuximab in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer

NCT01309126

Description:

Study BT-CL-PGG-CRC1031 is a Phase 3, open-label, randomized, multi-center study. Qualified subjects, who have KRAS wild type (WT) colorectal cancer will be randomized in a 2:1 ratio to treatment with either Imprime PGG and cetuximab or cetuximab alone. Subjects will be dosed until progression or discontinuation for some other reason. Efficacy will be assessed via Response Evaluation Criteria in Early Tumors 1.1 (RECIST 1.1); computed tomography (CT) scans will be conducted every 6 weeks. Safety, pharmacokinetics (PK), quality of life, and biomarker parameters will also be assessed.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 3

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">Imprime PGG</span> in Combination With <span class="go-doc-concept go-doc-intervention">Cetuximab</span> in Subjects With Recurrent or Progressive <span class="go-doc-concept go-doc-alteration">KRAS Wild Type</span> <span class="go-doc-concept go-doc-disease">Colorectal Cancer</span>

Title

  • Brief Title: Study of Imprime PGG in Combination With Cetuximab in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer
  • Official Title: A Phase 3 Open-Label, Randomized, Multicenter Study of Imprime PGG in Combination With Cetuximab (Erbitux) in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer
  • Clinical Trial IDs

    NCT ID: NCT01309126

    ORG ID: BT-CL-PGG-CRC1031

    Trial Conditions

    Colorectal Cancer

    Trial Interventions

    Drug Synonyms Arms
    Cetuximab Cetuximab (Erbitux) Arm 2: cetuximab

    Trial Purpose

    Study BT-CL-PGG-CRC1031 is a Phase 3, open-label, randomized, multi-center study. Qualified
    subjects, who have KRAS wild type (WT) colorectal cancer will be randomized in a 2:1 ratio
    to treatment with either Imprime PGG and cetuximab or cetuximab alone. Subjects will be
    dosed until progression or discontinuation for some other reason. Efficacy will be assessed
    via Response Evaluation Criteria in Early Tumors 1.1 (RECIST 1.1); computed tomography (CT)
    scans will be conducted every 6 weeks. Safety, pharmacokinetics (PK), quality of life, and
    biomarker parameters will also be assessed.

    Detailed Description

    Study BT-CL-PGG-CRC1031 is a Phase 3, open-label, randomized, multi-center study. Qualified
    subjects, who have KRAS WT colorectal cancer will be randomized in a 2:1 ratio to either:

    Arm 1: Imprime PGG and cetuximab or Arm 2: Cetuximab

    Approximately 795 subjects will be randomized into the study. Dosing will occur in 6-week
    cycles. Imprime PGG will be dosed at 4 mg/kg and will be administered weekly in each cycle
    (Weeks 1-6/Days 1, 8, 15, 22, 29, and 36) preceding the administration of cetuximab (Arm 1
    only). The initial cetuximab dose (both arms) will be 400 mg/m2 on Cycle 1/Day 1 and
    subsequent doses will be 250 mg/m2 administered weekly in each cycle (Weeks 1-6/Days 1, 8,
    15, 22, 29, and 36).

    Subjects will be dosed until progressive disease (PD) per RECIST 1.1 or discontinuation of
    study drug for other reasons; e.g., safety. Following completion of the treatment period of
    the study, subjects will be monitored for survival until death or loss to follow-up. Tumor
    measurements and determination of tumor responses will be evaluated according to RECIST 1.1.
    Safety, PK, quality of life, and biomarker parameters will also be assessed.

    Trial Arms

    Name Type Description Interventions
    Arm 1: Imprime PGG + cetuximab Experimental Biological/Vaccine + Drug
    Arm 2: cetuximab Active Comparator Drug Cetuximab

    Eligibility Criteria

    Inclusion Criteria:

    1. Is >18 years old;

    2. Has recurrent or metastatic carcinoma of the colon or rectum with documented
    histological or cytological confirmation;

    3. Must be KRAS WT;

    4. Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a
    target lesion according to RECIST 1.1;

    5. Has never received cetuximab or panitumumab, and has not received any treatment for
    colorectal cancer within 30 days prior to the first dose of study treatment under
    this protocol;

    6. Has an Eastern Cooperative Oncology Group (ECOG) score of 0-1, with a life expectancy
    of >3 months;

    7. Has received at least 2 prior chemotherapeutic regimens for colorectal cancer;

    8. Has adequate bone marrow reserve as evidenced by:

    - Absolute neutrophil count 1,500/L

    - Platelets 100,000/L;

    9. Has adequate renal function as evidenced by serum creatinine 2.5 the upper limit
    of normal (ULN) for the reference lab;

    10. Has adequate hepatic function as evidenced by:

    - Aspartate aminotransferase 3 ULN for the reference lab (5 ULN for subjects
    with known hepatic metastases)

    - Alanine aminotransferase 3 ULN for the reference lab (5 ULN for subjects
    with known hepatic metastases)

    - Bilirubin <1.5 mg/dL or direct bilirubin <1.0 mg/dL

    - Serum Albumin >3.0 gm/dL

    11. Has read, understood and signed the informed consent form (ICF) approved by the
    Independent Review Board/Independent Ethics Committee (IRB/IEC); and

    12. If the subject is a woman of childbearing potential or a fertile man, he/she must
    agree to use an effective form of contraception during the study and for 60 days
    following the last dose of study drug (an effective form of contraception is
    abstinence, a hormonal contraceptive, or a double-barrier method).

    Exclusion Criteria:

    1. Has a known hypersensitivity to cetuximab, murine proteins, or any component of
    cetuximab;

    2. Has a known hypersensitivity to baker's yeast or has an active yeast infection;

    3. Has had previous exposure to Betafectin or Imprime PGG;

    4. Has an active, uncontrolled infection;

    5. Has known untreated or symptomatic brain metastases;

    6. Had a second malignancy within the previous 5 years, except for basal cell carcinoma,
    cervical intra-epithelial neoplasia or treated prostate cancer with a
    prostate-specific antigen (PSA) of <2.0 ng/mL;

    7. Has known human immunodeficiency virus or acquired immune deficiency syndrome,
    hepatitis B, hepatitis C, connective tissue disease, or other clinical diagnosis,
    ongoing or intercurrent illness that in the Investigators opinion should preclude the
    subject from participation;

    8. If female, is pregnant or breast-feeding;

    9. Is receiving concurrent standard and/or investigational anti-cancer therapy or has
    received such therapy within a period of 30 days prior to the first scheduled day of
    dosing (investigational therapy is defined as treatment for which there is currently
    no regulatory-authority-approved indication); or

    10. Has previously received an organ or progenitor/stem cell transplant.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Survival (OS)

    Secondary Outcome Measures

    Progression Free Survival (PFS)

    Rate of complete response (CR)

    Rate of partial response (PR)

    Rate of overall response (CR + PR)

    Safety and tolerability of the dosing regimen as measured by the incidence and severity of adverse events observed in study participants

    Sparse pharmacokinetic profile of Imprime PGG will be determined to expand current Imprime PGG PK data

    Change in Quality of Life

    Trial Keywords

    Colorectal Cancer

    KRAS Wild Type

    Imprime PGG

    Cetuximab

    Phase 3

    Efficacy

    Safety

    Recurrent or Progressive KRAS Wild Type Colorectal Cancer