Clinical Trials /

Phase II Trial of Palbociclib in Patients With Metastatic Urothelial Cancer After Failure of First-Line Chemotherapy

NCT02334527

Description:

This multicenter phase II trial will evaluate palbociclib (PD-0332991) in patients with metastatic urothelial carcinoma (UC) with cyclin-dependent kinase inhibitor 2A (CDKN2A) (also referred to as p16) loss and positive Retinoblastoma (Rb) expression after failure of first-line chemotherapy.

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

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Phase II Trial of <span class="go-doc-concept go-doc-intervention">Palbociclib</span> (<span class="go-doc-concept go-doc-intervention">PD-0332991</span>) in Patients With Metastatic Urothelial <span class="go-doc-concept go-doc-disease">Cancer</span> (UC) After Failure of First-Line <span class="go-doc-concept go-doc-intervention">Chemotherapy</span>

Title

  • Brief Title: Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy
  • Official Title: Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy
  • Clinical Trial IDs

    NCT ID: NCT02334527

    ORG ID: LCCC 1406

    NCI ID: 14-2196

    Trial Conditions

    Metastatic Urothelial Carcinoma (UC)

    Trial Interventions

    Drug Synonyms Arms
    Palbociclib Single Arm (Single Arm Trial)

    Trial Purpose

    This multicenter phase II trial will evaluate palbociclib (PD-0332991) in patients with
    metastatic urothelial carcinoma (UC) with cyclin-dependent kinase inhibitor 2A (CDKN2A)
    (also referred to as p16) loss and positive Retinoblastoma (Rb) expression after failure of
    first-line chemotherapy.

    Detailed Description

    This multicenter phase II trial will evaluate palbociclib (PD-0332991) in patients with
    metastatic urothelial carcinoma (UC) with cyclin-dependent kinase inhibitor 2A (CDKN2A)
    (also referred to as p16) loss and positive Retinoblastoma (Rb) expression after failure of
    first-line chemotherapy. The study will enroll up to 40 patients to identify 36 evaluable
    patients, using a Simon's two-stage design, with a primary endpoint of progression free
    survival (PFS) at 4 months (PFS4). Secondary objectives include estimating median PFS,
    overall survival (OS), response rate (RR) and exploratory objectives include an evaluation
    of molecular predictors of response and resistance.

    Trial Arms

    Name Type Description Interventions
    Single Arm (Single Arm Trial) Other Palbociclib 125 mg capsule will be taken once per day orally and continuously for 3 weeks followed by 1 week off. Palbociclib

    Eligibility Criteria

    Inclusion Criteria:

    - Age 18 years

    - ECOG Performance status of 2 (see section 11.1, Appendix A)

    - Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis with
    Rb+/CDKN2A- based on immunohistochemistry (IHC) of tissue blocks or unstained slides
    performed within a CLIA-certified laboratory at UNC; if stage I of original cohort
    indicates futility, molecular requirement for eligibility will change to Rb+/CCND1
    overexpression (also based on IHC); see statistical section, section 8.0)

    - Metastatic disease that is not amenable to curative surgery or radiation

    - Prior treatment with two prior cytotoxic regimens; prior therapy must have
    consisted of at least one of the following: cisplatin, carboplatin, paclitaxel,
    docetaxel or gemcitabine. If the only prior cytotoxic therapy was administered in the
    perioperative i.e. neoadjuvant or adjuvant settings, patient is eligible provided the
    interval from end of therapy to the diagnosis of metastatic disease is less than one
    year.

    - Progressive disease during or after treatment with at least one of the agents listed
    above

    - At least one measurable disease site (as defined by RECIST1.1) that has not been
    previously irradiated

    - No prior therapy with a CDK 4/6 inhibitor

    - Washout period should be at least 2 weeks for prior chemotherapy or radiation therapy
    3.1.10 Resolution of all acute toxic effects of prior chemotherapy, radiotherapy,
    surgery to grade 1 per NCI CTCAEv4 except neuropathy which may be grade 2

    - No active brain metastases

    - Adequate bone marrow, liver and renal functions as assessed by the following:

    - Hemoglobin 8 g/dL;

    - Absolute neutrophil count 1,500/uL;

    - Platelets 75,000 g/uL;

    - Total bilirubin 1.5 times upper limit of normal (ULN);

    - ALT and AST 2.5 times ULN;

    - serum creatinine 2.5 times ULN;

    - Negative serum pregnancy test in women of child-bearing potential within 7 days of D1
    of treatment

    - If fertile, agree to use effective contraception (condom or other barrier methods,
    oral contraceptives, implantable contraceptives, intrauterine devices) during trial

    - Life expectancy greater than 3 months

    - Subject must be able to give written IRB approved informed consent and be able to
    follow protocol requirements

    Exclusion Criteria:

    - Any prior treatment with any investigational drug within the preceding 4 weeks

    - Any concurrent active malignancy requiring treatment (other than basal or squamous
    cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder
    tumors, other malignancies curatively treated > 3 years prior to study entry) or
    patients with adenocarcinoma of the prostate that has been surgically treated and
    with a post-treatment PSA that is non-detectable.

    - Unstable systemic disease or active uncontrolled infection

    - Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to
    study entry

    - Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville
    oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study
    medication and during the entire study due to potential CYP3A4 interaction with the
    study medication. Orange juice is allowed.

    - Intake of any herbal preparations or medications (including, but not limited to,
    Saint John's Wort and ginkgo biloba) and dietary supplements within 7 days prior to
    first dose of study drug

    - Unable or unwilling to discontinue use of any drug known to be a strong or moderate
    inhibitor or inducer of CYP3A4 (prohibited inducers and inhibitors must be
    discontinued within 2 weeks prior to first dose of study drug; see section 11.2
    Appendix B); unable or unwilling to discontinue use of any proton pump inhibitor; see
    section 11.2, Appendix B

    - Any malabsorption problem that, in the investigator's opinion, would prevent adequate
    absorption of the study drug

    - Inability to swallow oral medications

    - Pregnant or breast-feeding

    - Substance abuse, or medical, psychological or social conditions that may interfere
    with the patient's participation in the study or the evaluation of the study results

    - Other serious, ongoing, non-malignant disease or infection that would compromise
    protocol objectives

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival

    Secondary Outcome Measures

    Progression Free Survival (PFS) and Overall Survival (OS)

    Response Rate (RR)

    Number of participants with adverse events

    Trial Keywords

    metastatic urothelial carcinoma (UC)

    LCCC 1406

    Lineberger

    palbociclib