Clinical Trials /

Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors

NCT01999738

Description:

Phase 1A/B, multicenter, open-label, non-randomized, dose-escalation oncology study to evaluate the administration of EC1456 in advanced solid tumors. In part A, EC1456 will be dose escalated on 4 concurrently enrolling schedules. FR-positive expression on a 99mTc-etarfolatide scan is not required for inclusion in Part A. Part B of the study will confirm the maximum tolerated dose (MTD) and the recommended Phase 2 (RP2) dose of EC1456, and evaluate the efficacy of EC1456 in NSCLC all subtype patient populations with FR-positive cancer in up to three schedules (i.e., twice weekly, once weekly, and four times weekly). FR-positive expression on a 99mTc-etarfolatide scan is required for inclusion in Part B. Minimum length of patient participation is anticipated to be 10 weeks (two 3-week cycles followed by a 30 day follow-up period).

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Folic Acid</span>-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors

Title

  • Brief Title: Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors
  • Official Title: A Phase I Study of Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT01999738

    ORG ID: EC1456-01

    Trial Conditions

    Solid Tumors

    Triple-Negative Breast Cancer (TNBC)

    Advanced Non-Small Cell Lung Cancer (NSCLC)

    Ovarian Cancer

    Trial Interventions

    Drug Synonyms Arms
    EC1456 and etarfolatide (EC20) Part A - MTD

    Trial Purpose

    Phase 1, multicenter, open-label, non-randomized, dose-escalation oncology study to evaluate
    the administration of EC1456, BIW on Weeks 1 and 2 of a 3-week schedule (Part A), and to
    assess preliminary efficacy results in focused patients with triple-negative breast cancer
    (TNBC), advanced non-small cell lung cancer (NSCLC) and ovarian cancer treated at the MTD
    (Part B).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Part A - MTD Experimental EC1456 and etarfolatide (EC20)

    Eligibility Criteria

    Inclusion Criteria:

    Patients enrolled in Part A must receive the 99mTc- etarfolatide scan but they do not need
    to have FR-positive target lesions.

    Parts A and B:

    To qualify for enrollment, the following criteria must be met:

    - Patients must have the ability to sign an approved informed consent form (ICF).

    - Patients must be 18 years of age.

    - Patients must have histology confirmed metastatic or locally advanced solid tumor
    (preferably TNBC, NSCLC, ovarian, HCC) that has failed to respond to standard
    therapy, is not a candidate for standard therapy, or for which standard therapy does
    not exist.

    - Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
    0 or 1.

    - Patients must have at least one measurable lesion per RECIST v1.1 criteria/Modified
    RECIST for HCC.

    - For the purpose of obtaining a RECIST v1.1 baseline scan, patients must have a
    radiological evaluation conducted no more than 28 days prior to beginning study
    therapy. Note: For patients with a history of CNS metastasis, baseline radiological
    imaging must include evaluation of the brain (MRI preferred or CT with contrast).

    - Patients must have recovered (to baseline/stabilization) from prior
    cytotoxic-therapy-associated acute toxicities.

    - Patients with prior radiation therapy are eligible if they meet the following
    criteria:

    1. Previous radiation therapy is allowed to <25% of the bone marrow (Cristy and
    Eckerman, 1987).

    2. Prior radiotherapy must be completed at least 2 weeks before patient begins
    study therapy.

    3. Patient must have recovered from the acute toxic effects of the treatment before
    beginning study therapy.

    4. Palliative for pain or symptom control must be completed at least one week
    before patient begins study therapy, and these lesions must be excluded as
    target and non-target lesions.

    - Patients must have adequate organ function:

    1. Bone marrow reserve: Absolute neutrophil count (ANC) 1.5 x 109/L. Platelets
    100 x 109/L. Hemoglobin 9 g/dL.

    2. Cardiac:

    - Left ventricular ejection fraction (LVEF) equal to or greater than the institutional
    lower limit of normal. LVEF must be evaluated within 28 days prior to C1D1.

    - Cardiac Troponin I and T within normal limit. c) Hepatic: Total bilirubin 1.5 x the
    upper limit of normal (ULN). Alanine aminotransferase (ALT), aspartate
    aminotransferase (AST) 3.0 x ULN OR 5.0 x ULN for patients with liver metastases.

    d) Renal: Serum creatinine 1.5 x ULN, or for patients with serum creatinine > 1.5
    ULN, creatinine clearance 50 mL/min.

    - Patients of childbearing potential:

    1. All women of childbearing potential MUST have a negative serum pregnancy test
    within 1 week prior to the 99mTc-etarfolatide imaging procedure and within 1
    week prior to treatment with EC1456.

    2. Women of child bearing potential must practice an effective method of birth
    control (e.g., oral, transdermal or injectable contraceptives, intrauterine
    device [IUD], or double-barrier contraception, such as diaphragm and spermicidal
    jelly) for the duration of their participation in the trial through 90 days
    following the last dose of EC1456.

    3. Male patients who are sexually active must practice an effective method of birth
    control (e.g., condom and spermicidal jelly). Effective birth control methods
    should be used throughout study participation and for at least 90 days following
    the last dose of EC1456.

    Part B Only:

    - All patients in Part B must have TNBC, NSCLC or ovarian cancer.

    - All patients in Part B must have all target lesions FR-positive by 99mTc-etarfolatide
    scan.

    All patients in Part B must fulfill all other initial inclusion criteria (except inclusion
    criterion 3).

    Exclusion Criteria:

    Parts A and B:

    The presence of any of the following will exclude patients from the study:

    - More than 4 prior cytotoxic/biologics regimens for metastatic disease. Neoadjuvant
    and adjuvant treatments would not count towards this criterion (Note: hormonal
    therapy also would not count towards this criterion).

    - Chemotherapy, immunotherapy or biological therapy (including monoclonal antibodies)
    within 28 days prior to EC1456 administration.

    - Known hypersensitivity to the components of the study therapy or its analogs.

    - Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases.
    Note: Asymptomatic patients with stable CNS metastatic lesions in CT or MRI scans in
    the last 6 months are eligible.

    - Malignancies that are expected to alter life expectancy or may interfere with disease
    assessment. Patients with adequately treated non-melanoma skin cancer, carcinoma in
    situ of the cervix, or low-grade (Gleason score 6) localized prostate cancer,
    ductal carcinoma in situ (DCIS) and patients with prior history of malignancy who
    have been disease free for more than 3 years are eligible.

    - Serious cardiac illness or medical conditions such as unstable angina, pulmonary
    embolism, or uncontrolled hypertension.

    - Anti-folate therapy such as methotrexate for rheumatoid arthritis.

    - Pregnant or lactating women.

    - Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational
    therapy.

    - Active infections (e.g., hepatitis or HIV carriers)

    Part B Only:

    All patients in Part B must have received no more than two prior chemotherapeutic
    regimens.

    All patients in Part B must fulfill all other initial exclusion criteria (except exclusion
    criterion 1).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD)

    Secondary Outcome Measures

    Trial Keywords