Clinical Trials /

BGJ398 in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder

NCT02657486

Description:

The purpose of this study is to study the activity and effects of BGJ398 on bladder cancer tumors that are confined to the lining of the bladder.

Related Conditions:
  • Bladder Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">BGJ398</span> in Non-Muscle-Invasive <span class="go-doc-concept go-doc-disease">Urothelial Carcinoma</span> of the Bladder

Title

  • Brief Title: BGJ398 in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder
  • Official Title: Pilot Study of BGJ398 in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder
  • Clinical Trial IDs

    NCT ID: NCT02657486

    ORG ID: 15-090

    Trial Conditions

    Bladder Cancer

    Non-Muscle-Invasive Urothelial Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    BGJ398 BGJ398

    Trial Purpose

    The purpose of this study is to study the activity and effects of BGJ398 on bladder cancer
    tumors that are confined to the lining of the bladder.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    BGJ398 Experimental BGJ398 will be administered at a dose of 125 mg orally once daily on a three weeks on, one week off schedule. BGJ398

    Eligibility Criteria

    Inclusion Criteria:

    - Recurrent high-risk non-muscle-invasive bladder cancer after prior intravesical BCG
    therapy meeting all of the following criteria:

    - Histologically documented diagnosis of urothelial carcinoma confirmed by the
    Department of Pathology at MSKCC.

    - Documentation of activating FGFR3 mutation or gene fusion on an assay performed in a
    CLIA-certified laboratory.

    - History of high-grade, stage pTa non-muscle-invasive bladder cancer (NMIBC).

    - Clinical evidence of high-grade, stage pTa NMIBC.

    - Prior intravesical therapy with at least one induction course of BCG

    - Multiple papillary lesions with at least one amenable to marker tumor study (1 cm,
    non-invasive) OR solitary papillary lesion amenable to marker tumor study (1 cm,
    non-invasive)

    - Patient must be willing to consent to MSKCC protocol 12-245 ("Tumor Genomic Profiling
    in Patients Evaluated for Targeted Cancer Therapy"

    - Age 18 years or older.

    - Patient must be willing and able to comply with scheduled visits, treatment plan, and
    laboratory tests.

    - Patient must be able to swallow and retain oral medication.

    - Karnofsky performance status of 80.

    - Recovery from adverse events of previous systemic anti-cancer therapies to baseline
    or grade 1, except for:

    - Alopecia

    - Stable neuropathy of grade 2 due to prior cancer therapy

    - Women of childbearing potential, defined as all women physiologically capable of
    becoming pregnant, must agree to use highly effective methods of contraception during
    dosing and for 3 months following the discontinuation of study treatment.

    Highly effective contraception methods include:

    - Total abstinence (when this is in line with the preferred and usual lifestyle of the
    subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal,
    post-ovulation methods) and withdrawal are not acceptable methods of contraception.

    - Female sterilization (have had surgical bilateral oophorectomy with or without
    hysterectomy) or tubal ligation at least six weeks before study treatment. In case of
    oophorectomy alone, only when the reproductive status of the woman has been confirmed
    by follow-up hormone level assessment.

    - Male sterilization (at least 6 months prior to screening). For female subjects the
    vasectomized male partner should be the sole partner.

    - Combination of any two of the following (a+b, a+c, or b+c):

    1. Use of oral, injected or implanted hormonal methods of contraception or other
    forms of hormonal contraception that have comparable efficacy (failure rate
    <1%); for example, hormone vaginal ring or transdermal hormone contraception.

    2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)

    3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
    cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.

    Oral contraceptives (OC), injected or implanted hormonal methods are not allowed as the
    sole method of contraception because BGJ398 has not been characterized with respect to the
    potential to interfere with PK and/or the effectiveness of OCs.

    - If a woman is of non-childbearing potential, she must either:

    - Be post-menopausal as defined by 12 months of natural (spontaneous) amenorrhea
    with an appropriate clinical profile (e.g. age appropriate, history of vasomotor
    symptoms), OR

    - Have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal
    ligation at least six weeks ago. In the case of oophorectomy alone, the
    reproductive status of the woman must be confirmed by follow-up hormone level
    assessment.

    - Sexually active males must use a condom during intercourse while taking drug and for
    three months after the last dose of the study drug. They should not father a child
    during this period. Men who have undergone vasectomy are also required to use a
    condom during intercourse to prevent delivery of the drug via seminal fluid.

    Exclusion Criteria:

    - History of urothelial carcinoma in situ (CIS)

    - Clinical suspicion of CIS.

    - Evidence of >1 area of CIS not associated with papillary tumor.

    - Evidence of >7 tumors present in the bladder.

    - History or evidence of advanced urothelial carcinoma, including enlarged lymph nodes
    and/or distant metastases.

    - Evidence of upper tract urothelial carcinoma.

    - History of another primary malignancy within the last 3 years except:

    - Adequately treated in situ carcinoma of the cervix

    - Non-melanoma carcinoma of the skin

    - Any other curatively treated malignancy that has not been treated in the prior 3
    months and is not expected to require treatment for recurrence during the course
    of the study.

    - Patients who received prior treatment with a selective FGFR inhibitor.

    - Impairment of gastrointestinal (GI) function or GI disease that may significantly
    alter the absorption of oral BGJ398 (e.g., ulcerative diseases, uncontrolled nausea,
    vomiting, diarrhea, malabsorption syndrome, small bowel resection).

    - History and/or current evidence of tissue calcification including, but not limited
    to, the soft tissue, kidneys, intestine, myocardium, and lung with the exception of
    calcified lymph nodes and asymptomatic vascular calcification.

    - Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g.,
    parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis,
    etc.

    - Use of medications that increase serum levels of phosphorus and/or calcium (e.g.,
    calcium, phosphate, vitamin D, parathyroid hormone;) .

    - Current evidence of corneal or retinal disorder/keratopathy including, but not
    limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration,
    and/or keratoconjunctivitis, confirmed by ophthalmologic examination

    - Treatment with any of the following anti-cancer therapies prior to the first dose of
    BGJ398 within the stated timeframes:

    - Cyclical chemotherapy (intravenous) within a period of time that is shorter than
    the cycle length used for that treatment (e.g., 6 weeks for nitrosourea,
    mitomycin-C).

    - Biological therapy (e.g., antibodies - including bevacizumab) within a period of
    time that is 5 half-lives or 4 weeks, whichever is shorter, prior to
    starting study drug.

    - Continuous or intermittent small molecule therapeutics within a period of time
    that is 5 half-lives or 4 weeks (whichever is shorter) prior to starting
    study drug.

    - Any other investigational agents within a period of time that is 5 half-lives
    or less than the cycle length used for that treatment or 4 weeks (whichever is
    shortest) prior to starting study drug.

    - Wide field radiotherapy (including therapeutic radioisotopes such as strontium
    89) 4 weeks or limited field radiation for palliation 2 weeks prior to
    starting study drug.

    - Patients who are currently receiving treatment with agents that are known strong
    inducers or inhibitors of CYP3A4

    - Consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomelos,
    pomegranates, star fruits, Seville oranges or related products within 7 days prior to
    first dose

    - Use of herbal preparations/medications (including, but not limited to: St. John's
    wort, Kava, ephedra (ma huang), gingko bilboa, dehydroepiandrosterone (DHEA),
    yohimbe, saw palmetto, and ginseng within 7 days prior to first dose.

    - Use of medications that are known to prolong the QT interval and/or are associated
    with a risk of Torsades de Pointes 7 days prior to first dose

    - Use of amiodarone within 90 days prior to first dose

    - Current use of therapeutic doses of warfarin sodium or any other coumadin-derivative
    anticoagulants. Heparin and/or low molecular weight heparins are allowed.

    - Insufficient bone marrow function as evidenced by:

    - ANC <1,000/mm3 [1.0 x 10^9/L]

    - Platelets < 75,000/mm3 [75 x 10^9/L]

    - Hemoglobin < 10.0 g/dL

    - Insufficient hepatic and renal function as evidenced by:

    - Total bilirubin > 1.5x ULN

    - AST/SGOT and ALT/SGPT > 2x ULN

    - Serum creatinine > 1.5x ULN

    - Calculated (using the CKD-EPI equation) or measured creatinine clearance < 75%
    LLN

    - Calcium-phosphate homeostasis as evidenced by:

    - Inorganic Phosphorus outside of normal limits

    - Total serum calcium (can be corrected) outside of normal limits

    - Clinically significant cardiac disease including any of the following:

    - Congestive heart failure requiring treatment (NYHA grade 2)

    - LVEF < 50 as determined by MUGA scan or ECHO

    - Uncontrolled hypertension (refer to WHO-ISH guidelines

    - History or presence of clinically significant ventricular arrhythmias, atrial
    fibrillation, resting bradycardia, or conduction abnormality

    - Unstable angina pectoris or acute myocardial infarction 3 months prior to
    starting study drug

    - QTcF > 480 msec (males and females)

    - History of congenital long QT syndrome

    - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
    female after conception and until the end of gestation, confirmed by a positive hCG
    laboratory test.

    - Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C
    infection.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    tumor response

    Secondary Outcome Measures

    Trial Keywords

    BGJ398

    15-090