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Phase 2a Study of BAX69 and 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer

NCT02448810

Description:

The purpose of this study is to evaluate the safety and tolerability of BAX69 in combination with 5-fluorouracil (5-FU)/leucovorin (LV) or panitumumab to determine the recommended phase II dose (RP2D) of each combination; and to compare the efficacy between BAX69 in combination with 5-FU/LV for subjects with KRAS or NRAS mutated tumor (mt) or panitumumab, for subjects with KRAS and NRAS wild type tumor (wt) and standard of care (SoC) per investigator choice as third or fourth treatment line in subjects with progressive measurable metastatic colorectal cancer (mCRC).

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Phase 2a Study of BAX69 and <span class="go-doc-concept go-doc-intervention">5-FU</span>/<span class="go-doc-concept go-doc-intervention">Leucovorin</span> or <span class="go-doc-concept go-doc-intervention">Panitumumab</span> Versus <span class="go-doc-concept go-doc-intervention">Standard of Care</span> in Subjects With Metastatic <span class="go-doc-concept go-doc-disease">Colorectal Cancer</span>

Title

  • Brief Title: Phase 2a Study of BAX69 and 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer
  • Official Title: A Phase 2a Randomized, Open-label Study to Assess the Safety, Tolerability, and Efficacy of BAX69 in Combination With 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer
  • Clinical Trial IDs

    NCT ID: NCT02448810

    ORG ID: 391401

    NCI ID: 2015-000896-28

    Trial Conditions

    Metastatic Colorectal Cancer

    Trial Interventions

    Drug Synonyms Arms
    Standard of Care Part 2: Standard of Care- Subjects with KRAS or NRAS mutated

    Trial Purpose

    The purpose of this study is to evaluate the safety and tolerability of BAX69 in combination
    with 5-fluorouracil (5-FU)/leucovorin (LV) or panitumumab to determine the recommended phase
    II dose (RP2D) of each combination; and to compare the efficacy between BAX69 in combination
    with 5-FU/LV for subjects with KRAS or NRAS mutated tumor (mt) or panitumumab, for subjects
    with KRAS and NRAS wild type tumor (wt) and standard of care (SoC) per investigator choice
    as third or fourth treatment line in subjects with progressive measurable metastatic
    colorectal cancer (mCRC).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Part 1: Subjects with mutated tumor (mt) (KRAS or NRAS) Experimental Subjects stratified according to their mutation status.
    Part 1: Subjects with wild-type (wt) tumor (KRAS and NRAS wt) Experimental Subjects stratified according to their mutation status.
    Part 2: Subjects with KRAS or NRAS mutated Experimental Subjects stratified according to their mutation status.
    Part 2: Subjects with KRAS and NRAS wt tumor Experimental Subjects stratified according to their mutation status.
    Part 2: Standard of Care- Subjects with KRAS or NRAS mutated Active Comparator Subjects stratified according to their mutation status. Standard of Care
    Part 2: Standard of Care- Subjects with KRAS and NRAS wt tumor Active Comparator Subjects stratified according to their mutation status.Subjects stratified according to their mutation status.

    Eligibility Criteria

    Inclusion Criteria:

    1. Provision of a signed informed consent

    2. Male and female subjects 18 years of age and older at the time of screening

    3. Subjects who progressed after receiving at least 2, but no more than 3, prior SoC
    treatment lines

    4. Anticipated life expectancy >3 months at the time of screening

    5. Weight between 40 kg and 180 kg

    6. Histologically or cytologically confirmed diagnosis of CRC

    7. Metastatic CRC not amenable to surgical resection

    8. Known KRAS and NRAS mutation status (if unknown status for either of these genes, and
    no archival tissues is available, a fresh tumor biopsy will be made)

    9. At least 1 measurable lesion as defined by RECIST v1.1

    10. ECOG PS of 0-2

    11. Adequate hematological function, defined as:

    1. Platelet count 100,000/L

    2. Prothrombin time and activated partial thromboplastin time (aPTT) < 1.5 times
    the upper limit of normal (ULN)

    3. Absolute neutrophil count (ANC) 1,000/L

    4. Hemoglobin 9 g/dL, without the need for transfusion in the 2 weeks prior to
    screening

    12. Adequate renal function, defined as serum creatinine 2.0 times ULN and creatinine
    clearance > 50 mL/min

    13. Adequate liver function, defined as:

    1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

    2.5 times ULN for subjects without liver metastases, or 5 times ULN in the
    presence of liver metastases

    2. Bilirubin 2.0 times ULN, unless subject has known Gilbert's syndrome

    14. Adequate venous access

    15. For female subjects of childbearing potential, the subject presents with a negative
    serum pregnancy test at screening and agrees to employ 2 forms of adequate birth
    control measures, including at least 1 barrier method (eg, diaphragm with spermicidal
    jelly or foam, or [for male partner] condom) throughout the course of the study and
    for at least 90 days after the last administration of BAX69. Other acceptable
    contraceptive measures include birth control pills/patches or intrauterine devices

    16. For male subjects, the subject must agree to use adequate contraceptive measures
    including at least 1 barrier method (eg, condom with spermicidal jelly or foam and
    [for the female partner] diaphragm with spermicidal jelly or foam, birth control
    pills/patches, or intrauterine device) and abstain from sperm donation throughout the
    course of the study and for at least 90 days after the last administration of BAX69

    17. Subject is willing and able to comply with the requirements of the protocol.

    Exclusion Criteria:

    1. Known central nervous system metastases

    2. Prior malignancy(s) within the past 3 years, with the exception of curatively treated
    basal or squamous cell carcinoma of the skin, locally advanced prostate cancer,
    ductal carcinoma in situ of breast, in situ cervical carcinoma and superficial
    bladder cancer

    3. Prior treatment with panitumumab for subjects with KRAS and NRAS wt tumor

    4. Residual AE from previous treatment > Grade 1

    5. Prior intolerance to fluoropyrimidine for subjects with KRAS or NRAS mut tumor

    6. Myocardial infarction within 6 months prior to C1D1, and/or prior diagnoses of
    congestive heart failure (New York Heart Association Class III or IV), unstable
    angina, unstable cardiac arrhythmia requiring medication; and/or the subject is at
    risk for polymorphic ventricular tachycardia (eg, hypokalemia, family history or long
    QT syndrome)

    7. Uncontrolled hypertension defined as systolic blood pressure 160 mmHg and/or
    diastolic blood pressure 100 mmHg confirmed upon repeated measures

    8. LVEF < 40% as determined by echocardiogram performed at screening or within 90 days
    prior to C1D1

    9. QT/QTc interval > 450 msec, as determined by screening ECG performed no earlier than
    1 week before C1D1

    10. Prior anti-tumor therapy (chemotherapy, radiotherapy, antibody therapy, molecular
    targeted therapy, retinoid therapy or hormonal therapy) within 4 weeks prior to C1D1.

    11. Major surgery within 4 weeks prior to C1D1

    12. Active joint inflammation or history of inflammatory arthritis or other immune
    disorder involving joints

    13. Active infection involving IV antibiotics within 2 weeks prior to C1D1

    14. Known history of, or active hepatitis B virus (HBV), hepatitis C virus (HCV) or
    active tuberculosis

    15. Known history of human immunodeficiency virus (HIV) type 1/2 or other
    immunodeficiency disease

    16. Subject has received a live vaccine within 4 weeks prior to C1D1

    17. Known hypersensitivity to any component of recombinant protein production by CHO
    cells

    18. Exposure to an investigational product or investigational device in another clinical
    study within 4 weeks prior to C1D1, or is scheduled to participate in another
    clinical study involving an investigational product or device during the course of
    this study

    19. Subject is nursing or intends to begin nursing during the course of the study

    20. Any disorder or disease, or clinically significant abnormality on laboratory or other
    clinical test(s) (eg, blood tests, ECG), that in medical judgment of the investigator
    may impede the subject's participation in the study, pose increased risk to the
    subject, and/or confound the results of the study

    21. Subject is a family member or employee of the investigator

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Occurrence of Dose Limiting Toxicity (DLT)

    Progression-Free Survival (PFS)

    Secondary Outcome Measures

    Occurrence of binding and/or neutralizing BAX69 antibodies

    Incidence and severity of infusion reactions after BAX69

    Occurrence of serious adverse events (SAEs) and/or treatment-emergent adverse events (TEAEs)

    Response evaluation according to RECIST v1.1

    Overall survival (OS) defined as time from randomization to death of any cause

    Quality of Life (QoL) measure - European Organization for Research and Treatment of Cancer Quality of life Questionnaire Core 30 (EORTC QLQ-C30) questionnaire

    Trial Keywords