Clinical Trials /

Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

NCT02668666

Description:

This is a non-randomized, open-label, single-arm, multicenter, phase II study of palbociclib in combination with tamoxifen in women with HR(+)/HER2(-) advanced breast cancer who have not received prior systemic anticancer therapies for their advanced/metastatic disease.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Palbociclib</span> in Combination With <span class="go-doc-concept go-doc-intervention">Tamoxifen</span> as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

Title

  • Brief Title: Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer
  • Official Title: A Single Arm Phase II Study of Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer: Big Ten Cancer Research Consortium BTCRC-BRE15-016
  • Clinical Trial IDs

    NCT ID: NCT02668666

    ORG ID: BTCRC BRE15-016

    Trial Conditions

    Hormone Receptor Positive Malignant Neoplasm of Breast

    Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

    Estrogen Receptor Positive Breast Cancer

    Progesterone Receptor Positive Tumor

    Metastatic Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Palbociclib Ibrance Investigational Treatment
    Tamoxifen Nolvadex Investigational Treatment

    Trial Purpose

    This is a non-randomized, open-label, single-arm, multicenter, phase II study of palbociclib
    in combination with tamoxifen in women with HR(+)/HER2(-) advanced breast cancer who have
    not received prior systemic anticancer therapies for their advanced/metastatic disease.

    Detailed Description

    OUTLINE: This is a multi-center trial.

    INVESTIGATIONAL TREATMENT:

    - Palbociclib 125 mg will be administered orally once daily on days 1-21 (D1-D21) of each
    28-day cycle. Subjects will not take palbociclib on D22-D28.

    - Tamoxifen 20 mg will be administered orally once daily for every day of the 28-day
    cycle (i.e., continuously).

    Palbociclib should be taken with food in combination with tamoxifen. Subjects should take
    their dose at approximately the same time each day.

    It is encouraged, but not mandatory, that premenopausal subjects will also receive treatment
    with goserelin or equivalent (e.g., Lupron) given as an injectable subcutaneous implant on
    D1 of every 28 days cycle or every 3 months.

    Disease assessments will be performed at the completion of every 2 cycles.

    Treatment will continue until disease progression, unacceptable toxicity, subject refusal,
    or subject death either from progression of disease, the therapy itself, or from other
    causes. Subjects who voluntarily stop the study, have progressive disease, or unacceptable
    toxicities will be followed for a total of 24 months after discontinuation of study drug.

    To demonstrate adequate organ function, all screening labs should be performed within 14
    days prior to registration for protocol therapy:

    Hematological (must meet ALL of the following criteria):

    - Absolute neutrophil count (ANC) 1.5 10 9/L

    - Hemoglobin 9 g/dL

    - Platelet count 100 10 9/L

    Renal (must meet ONE of the following criteria):

    - Serum creatinine 1.5 ULN

    - Serum creatinine > 1.5 ULN, estimated glomerular filtration rate (eGFR) 40 mL/min

    Hepatic (must meet ALL of the following criteria):

    - Aspartate aminotransferase (AST) 2.5 ULN or 5 ULN for subjects with known
    hepatic metastases

    - Alanine aminotransferase (ALT) 2.5 ULN or 5 ULN for subjects with known hepatic
    metastases

    - Total serum bilirubin 1.5 ULN

    Trial Arms

    Name Type Description Interventions
    Investigational Treatment Experimental 71 subjects will be enrolled to determine progression-free survival (PFS) in subjects with HR(+)/HER2(-) advanced breast cancer who have not received prior systemic anti-cancer therapies. Palbociclib 125 mg will be administered orally once daily on days D1-D21 of each 28-day cycle. Subjects will not take palbociclib on D22-D28. Tamoxifen 20 mg will be administered orally once daily for every day of the 28-day cycle (i.e., continuously). Palbociclib, Tamoxifen

    Eligibility Criteria

    Inclusion Criteria:

    Subjects must meet all of the following applicable inclusion criteria to participate in
    this study:

    - Female 18 years of age at time of consent. NOTE: Both pre- and post-menopausal
    women are eligible. Pre-menopausal status is defined as either:

    - Last menstrual period within the last 12 months.

    - In case of therapy-induced amenorrhea, plasma estradiol and /or FSH is in the
    premenopausal range per local normal range.

    - Women with locoregional recurrent or metastatic disease, as determined by biopsy of
    the metastatic lesion, not amenable to curative therapy.

    - Histologically and/or cytologically confirmed diagnosis of ER positive and/or PR
    positive (ER >1%, PR >1%), HER2 negative metastatic breast cancer. NOTE: Subject has
    HER2-negative breast cancer (based on most recently analyzed biopsy) is defined as a
    negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a
    negative in situ hybridization (FISH, CISH, or SISH) test is required by local
    laboratory testing.

    - Metastatic disease evaluable on imaging studies. Subjects may have measurable disease
    as per RECIST 1.1 or bone-only disease. Bone-only subjects are eligible if their
    disease can be documented/ evaluated by bone scans, CT or MRI. Their disease will be
    assessed using MDA criteria.

    - No prior systemic anti-cancer therapy for advanced HR+ disease. NOTE: Subjects
    receiving adjuvant treatment with aromatase inhibitors at time of recurrence are
    allowed to participate.

    - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

    - Provided written informed consent and Health Insurance Portability and Accountability
    Act of 1996 (HIPAA) authorization for release of personal health information,
    approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC).
    NOTE: HIPAA authorization may be included in the informed consent or obtained
    separately.

    - Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A
    negative serum or urine pregnancy test is required within 72 hours of study
    registration from women of childbearing potential. If the urine test cannot be
    confirmed as negative, a serum pregnancy test will be required.

    - Women of childbearing potential (WOCP) must be willing to use two effective methods
    of birth control such as use of a double barrier method (condoms, sponge, diaphragm,
    or vaginal ring with spermicidal jellies or cream), or total abstinence for the
    course of the study until 120 days after the last dose of study drug. The use of
    hormonal contraceptives is discouraged. NOTE: Women are considered to be of
    childbearing potential unless they are postmenopausal for at least 12 consecutive
    months or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or
    hysterectomy).

    - Willingness and ability to comply with scheduled visits, treatment plans, laboratory
    tests, and other study procedures.

    Exclusion Criteria:

    Subjects meeting any of the criteria below may not participate in the study:

    - Prior treatment with any CDK 4/6 inhibitor.

    - Confirmed diagnosis of HER2 positive disease.

    - Known uncontrolled or symptomatic CNS metastases. Subjects with known brain
    metastasis will only be eligible after their tumors have been treated with definitive
    resection and /or radiotherapy and they are neurologically stable for at least 1
    month off steroids.

    - Subjects with advanced, symptomatic, visceral spread that have life expectancy less
    than 4 months.

    - Prior (neo)adjuvant treatment with tamoxifen within the 12 months before study entry.

    - Prior history of blood clots, pulmonary embolism or deep vein thrombosis.

    - Subjects with impairment of gastrointestinal (GI) function or GI disease that may
    significantly alter the absorption of the study drugs (e.g., ulcerative diseases,
    uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
    resection).

    - Subject has a concurrent malignancy or malignancy within 3 years of randomization,
    with the exception of adequately treated basal cell carcinoma, squamous cell skin
    carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.

    - 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.

    - Subject is currently receiving any of the following substances and cannot be
    discontinued 7 days prior to the start of the treatment:

    - Known strong inducers or inhibitors of CYP3A4/5, including grapefruit,
    grapefruit hybrids, pomelos, star-fruit, and Seville oranges.

    - Medications that have a narrow therapeutic window and are predominantly
    metabolized through CYP3A4/5.

    - Known strong inducers or inhibitors of CYP2D6.

    - Subject has had major surgery within 14 days prior to starting study drug or has not
    recovered from major side effects of surgery.

    - Known history of human immunodeficiency virus [(HIV) HIV 1/2 antibodies].

    - Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
    [qualitative] is detected) (testing not mandatory)

    - Any clinically significant infection defined as any acute viral, bacterial, or fungal
    infection that requires specific treatment. NOTE: Anti-infective treatment must be
    completed 7 days prior to study registration.

    - Any other severe, uncontrolled medical condition, including uncontrolled diabetes
    mellitus or unstable congestive heart failure

    - Known allergy to palbociclib or any of its excipients

    - Presence of any non-healing wound, fracture, or ulcer within 28 days prior to study
    registration.

    - Any condition that, in the opinion of the investigator, might jeopardize the safety
    of the subject or interfere with protocol compliance.

    - Any mental or medical condition that prevents the subject from giving informed
    consent or participating in the trial.

    - Treatment with any investigational agent within 28 days prior to registration for
    protocol therapy and the subject must have recovered from the acute toxic effects of
    the regimen.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Response Rates in Subjects with HR(+)/HER2(-) Advanced Breast Cancer who have not Received Prior Systemic Anti-Cancer Therapies for their Advanced/Metastatic Disease Treated with Palbociclib in Combination with Tamoxifen

    Secondary Outcome Measures

    Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Progression-Free Survival (PFS) in Subjects with HR(+)/HER2(-) Advanced Breast Cancer who have not Received Prior Systemic Anti-Cancer Therapies for their Advanced/Metastatic Disease Treated with Palbociclib in Combination with Tamoxifen

    Clinical Benefit Rate (CBR) in Subjects with HR(+)/HER2(-) Advanced Breast Cancer who have not Received Prior Systemic Anti-Cancer Therapies for their Advanced/Metastatic Disease Treated with Palbociclib in Combination with Tamoxifen

    Overall Survival (OS) in Subjects with HR(+)/HER2(-) Advanced Breast Cancer who have not Received Prior Systemic Anti-Cancer Therapies for their Advanced/Metastatic Disease Treated with Palbociclib in Combination with Tamoxifen

    Trial Keywords

    Palbociclib

    Tamoxifen

    CDK4/6 Inhibitor