Phase 2 Study With Abraxane (Nab®Paclitaxel) in Metastatic Colorectal Cancer
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: ABI-007
Intervention MeSH terms: Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Colorectal Cancer; nab®Paclitaxel; Response Evaluation in Solid Tumors; Progression Free Survival; Overall Survival; Duration of Response; RAS

Summary:

      The purpose of this study is to evaluate the safety and efficacy of Abraxane (nab-paclitaxel)
      in subjects with previously treated metastatic colorectal cancer. Subjects will be placed
      into two separate cohorts based on their RAS mutation status.
    

Eligibility criteria:

        Inclusion Criteria: - 1. Subject is ≥ 18 years old at the time of signing the Informed
        Consent Form 2. Subject has histological or cytological diagnosis of adenocarcinoma of the
        colon or rectum, with evidence of metastasis 3. Subject has a known KRAS mutation status
        (mutated or wild-type). NRAS mutation status may be unknown. 4. Subject has documented
        disease progression ≤ 2 months after the last administration of the last standard therapy.
        a. Subjects treated with oxaliplatin in the adjuvant setting, should have progressed during
        or within 6 months of completion of adjuvant therapy 5. Subject has either received prior
        treatment or was not a candidate for prior treatment, with fluoropyrimidine, oxaliplatin,
        irinotecan and an anti-VEGF therapy (e.g. bevacizumab or ziv-aflibercept); and if RAS
        wild-type tumors, an anti-EGFR therapy (e.g. cetuximab or panitumumab). 6. Subject has
        Eastern Cooperative Oncology Group performance status 0 or 1 7. Subject has
        radiographically-documented measurable disease, as per Response Evaluation Criteria in
        Solid Tumors version 1.1 criteria 8. Subject has adequate organ functions, evidenced by the
        following: a. Aspartate Aminotransferase (SGOT), Alanine Transaminase (SGPT) ≤ 2.5 × upper
        limit of normal range, or < 5 x upper limit of normal range if liver metastasis present b.
        Total bilirubin ≤ 1.5 × upper limit of normal range c. Creatinine ≤ 1.5 × upper limit of
        normal range 9. Subject has adequate bone marrow function, evidenced by the following: a.
        Absolute neutrophil count ≥ 1.5 × 109 cells/millimeters3 b. Platelets ≥ 100 × 109
        cells/millimeters3 (transfusion independent, defined as not receiving platelet transfusions
        within 7 days prior to laboratory sample) c. Hemoglobin ≥ 9 grams/decilitre (transfusion is
        permitted to fulfill this criterion) 10. Females of child-bearing potential (defined as a
        sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the
        uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not
        been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at
        any time during the preceding 24 consecutive months]) must: a. Either commit to true
        abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or agree
        to use, and be able to comply with, effective contraception without interruption, 28 days
        prior to starting Investigational Product therapy (including dose interruptions), and for 3
        months following the last dose of Investigational Product; and b. Have a negative serum
        pregnancy test (β -human Chorionic Gonadotrophin) result at screening and agree to ongoing
        pregnancy testing during the course of the study, and after the end of study therapy. This
        applies even if the subject practices true abstinence* from heterosexual contact. * True
        abstinence is acceptable when this is in line with the preferred and usual lifestyle of the
        subject. Note: Periodic abstinence (e.g, calendar, ovulation, symptothermal, post-ovulation
        methods) and withdrawal are not acceptable methods of contraception. 11. Male subjects must
        practice true abstinence* or agree to use a condom during sexual contact with a pregnant
        female or a female of childbearing potential while participating in the study, during dose
        interruptions and for 6 months following Investigational Product discontinuation, even if
        he has undergone a successful vasectomy. 12. Subject must understand and voluntarily sign
        an Informed Consent Form prior to any study related assessments or procedures being
        conducted. 13. Subject must be able to adhere to the study visit schedule and other
        protocol requirements. Exclusion Criteria: - 1. Subject has current or a history of brain
        metastasis. In subjects who are symptomatic, a brain scan is required to exclude
        metastasis. 2. Subject has ≥ National Cancer Institute Common Terminology Criteria for
        Adverse Events grade 2 peripheral neuropathy at screening 3. Subject has had prior
        treatment with regorafenib 4. Subject has received radiotherapy ≤ 4 weeks or limited field
        radiation for palliation ≤ 2 weeks prior to starting Investigational Product, and/or from
        whom ≥ 30% of the bone marrow was irradiated. Radiation therapy to a target lesion is
        permitted only if there has been clear progression of the lesion since radiation was
        completed. 5. Subject has had major surgery within 14 days prior to starting
        Investigational Product or has not recovered from postoperative complications 6. Subject
        has not recovered from the acute toxic effects of prior anticancer therapy, radiation or
        major /significant trauma 7. Subject has a history of allergy or hypersensitivity to
        nab-paclitaxel or any of the excipients 8. Subject has a known history of the following
        within 6 months prior to enrollment (the decision to include the subject in the study): a
        myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass
        graft, New York Heart Association Class III-IV heart failure, uncontrolled hypertension,
        clinically significant cardiac dysrhythmia or Electrocardiogram abnormality,
        cerebrovascular accident, transient ischemic attack, or seizure disorder 9. Subject has a
        known infection with hepatitis B or C, or history of human immunodeficiency virus
        infection, or subject receiving immunosuppressive or myelosuppressive medications that
        would in the opinion of the investigator, increase the risk of serious neutropenic
        complications 10. Subject has an active, uncontrolled bacterial, viral, or fungal
        infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the
        infection without improvement despite appropriate antibiotics, antiviral therapy, and/or
        other treatment 11. Subject has any other malignancy within 5 years prior to enrolment,
        with the exception of adequately treated in-situ carcinoma of the cervix, uteri, or
        non-melanomatous skin cancer (all treatment of which should have been completed 6 months
        prior to enrollment) 12. Subject has a history of connective tissue disorders (eg, lupus,
        scleroderma, arteritis nodosa) 13. Subject has a history of interstitial lung disease ,
        history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis,
        idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
        14. Subject has any other concurrent severe and/or uncontrolled medical condition that
        would, in the investigator's judgment, contraindicate subject participation in the clinical
        study (e.g. chronic pancreatitis, chronic active hepatitis, etc.) 15. Subject is enrolled
        in any other clinical protocol or investigational study with an interventional agent or
        assessments that may interfere with study procedures 16. Subject has any significant
        medical condition, laboratory abnormality, or psychiatric illness that would prevent the
        subject from participating in the study 17. Subject has any condition that confounds the
        ability to interpret data from the study 18. Subject is unwilling or unable to comply with
        study procedures 19. Subject is a pregnant or nursing female