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Open Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Subjects With Advanced/Relapsed Solid Tumors

NCT02307240

Description:

This is a Phase I, open-label, multi-center trial designed to evaluate the safety, tolerability and pharmacokinetics of CUDC-907 administered orally to subjects with advanced/relapsed solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Open Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Subjects With Advanced/Relapsed Solid Tumors

Title

  • Brief Title: Open Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Subjects With Advanced/Relapsed Solid Tumors
  • Official Title: Phase I Open Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered CUDC-907, an HDAC and PI3K Inhibitor, in Subjects With Advanced/Relapsed Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02307240

    ORG ID: CUDC-907-102

    Trial Conditions

    NUT Midline Carcinoma

    Breast Cancer

    Solid Tumor

    Trial Interventions

    Drug Synonyms Arms
    CUDC-907 CUDC-907 - 3x/week (TIW), CUDC-907 - five days on/two days off, CUDC-907 four days on/three days off

    Trial Purpose

    This is a Phase I, open-label, multi-center trial designed to evaluate the safety,
    tolerability and pharmacokinetics of CUDC-907 administered orally to subjects with
    advanced/relapsed solid tumors.

    Detailed Description

    This is a Phase I, open-label, multi-center trial designed to evaluate the safety,
    tolerability and pharmacokinetics of CUDC-907 administered orally to subjects with
    advanced/relapsed solid tumors. The following dosing schedules may be examined, each
    consisting of 21-day treatment cycles:

    1. Three days weekly on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 (TIW schedule).

    2. Five days on/two days off on Days 1 to 5, 8 to 12, and 15 to 19 (5/2 schedule).

    3. Four days on/three days off on Days 1 to 4, 8 to 11, and 15 to 18 (4/3 schedule).

    Trial Arms

    Name Type Description Interventions
    CUDC-907 - 3x/week (TIW) Experimental 120 -150 mg/day CUDC-907, oral administration, three days weekly until disease progression or other discontinuation criteria are met. CUDC-907
    CUDC-907 - five days on/two days off Experimental 60 -90 mg/day CUDC-907, oral administration, five days on/two days off until disease progression or other discontinuation criteria are met. CUDC-907
    CUDC-907 four days on/three days off Experimental 60 -90 mg/day CUDC-907, oral administration, four days on/three days off until disease progression or other discontinuation criteria are met. CUDC-907

    Eligibility Criteria

    Inclusion Criteria:

    1. Subjects 18 years of age

    2. Histopathologically confirmed diagnosis of advanced solid tumor such as breast cancer
    or midline carcinoma with NUT rearrangement, that has progressed despite standard
    therapy, or for which no standard therapy exists. In the case of breast cancer, this
    must be ER+ or PR+, Her2 negative disease (women only) with disease progression on at
    least one prior hormonal therapy for advanced/metastatic disease or disease relapse
    while on adjuvant hormonal therapy

    3. Measurable or evaluable disease

    4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

    5. Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments or
    radiotherapy (excluding alopecia). Note: for subjects with HR+/Her2 negative breast
    cancer only: ongoing treatment with any of the following: tamoxifen, anastrozole,
    exemestane or letrozole is allowed

    6. Adequate hematologic and organ function as evidenced by the following laboratory
    studies within two weeks (14 days) of study enrollment: Absolute neutrophil count
    1,500/L; platelets 100,000/L; hemoglobin >9 g/dL; creatinine 1.5x upper limit of
    normal (ULN); total bilirubin (Tbili) 1.5x ULN; aspartate aminotransferase/alanine
    aminotransferase (AST/ALT) 2.5x ULN; serum albumin >3 g/dl; partial thromboplastin
    time or INR <1.2 x ULN (unless receiving therapeutic anticoagulation)

    7. For subjects with diabetes, adequate blood sugar control as evidenced by a hemoglobin
    A1c value <8%

    8. Women of child-bearing potential must have a negative serum or urine pregnancy test

    9. Men and women of child-bearing potential must agree to use adequate birth control
    throughout their participation in the study and for 30 days following the last study
    treatment

    10. Able to provide written informed consent and follow protocol requirements

    Exclusion Criteria:

    1. Systemic anticancer therapy within three weeks of study entry, except for
    nitrosoureas or mitomycin C within six weeks

    2. Radiotherapy within one week prior to starting study treatment

    3. Other investigational agent(s) within 21 days prior starting to study treatment

    4. Symptomatic central nervous system (CNS) involvement or lymphangitic metastasis.
    Stable or improving CNS disease that is not under active treatment after receipt of
    adequate therapy is allowed

    5. Uncontrolled or severe cardiovascular disease, including myocardial infarction or
    unstable angina within six months prior to study treatment, New York Heart
    Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias
    requiring medication for treatment, clinically significant pericardial disease or
    cardiac amyloidosis

    6. Diabetes mellitus uncontrolled by medication

    7. Ongoing diarrhoea defined as more than one watery stool/day

    8. Serious infection requiring systemic antibiotic therapy within 14 days prior to study
    treatment

    9. Immunosuppressive medication within 7 days prior to first dose of CUDC-907. Inhaled
    and topical corticosteroids are permitted, as is replacement dosing of steroids
    (defined as <30 mg/day hydrocortisone or the equivalent) provided that the subject
    has been on a stable or tapering dose for at least 14 days prior to the first dose of
    CUDC-907

    10. Second primary malignancy within two years of study entry that requires active
    treatment

    11. Known gastrointestinal condition that would interfere with swallowing or oral
    absorption/tolerance of CUDC-907

    12. Known positive status for human immunodeficiency virus (HIV) or hepatitis B surface
    antigen, or known or suspected hepatitis C infection

    13. Pregnancy or ongoing breast-feeding status

    14. Unstable or clinically significant concurrent condition (e.g. medical or
    psychological) that would, in the opinion of the investigator, jeopardize subject
    safety and/or compliance with the protocol

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    To establish the maximum tolerated dose/biologically effective dose (MTD/BED) and recommended Phase 2 dose (RP2D) of CUDC-907

    Secondary Outcome Measures

    To assess the pharmacokinetics (PK) of CUDC-907; Pharmacokinetic parameters will include area under the concentration-time curve (AUC).

    To assess the safety and tolerability of CUDC-907; Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events

    To assess the preliminary anti-cancer activity of CUDC-907

    Trial Keywords

    NMC