Clinical Trials /

Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

NCT01272037

Description:

This randomized phase III clinical trial studies how well tamoxifen citrate, anastrozole, letrozole, or exemestane with or without chemotherapy work in treating patients with breast cancer that has spread from where it began in the breast to surrounding normal tissue (invasive). Estrogen can cause the growth of breast cancer cells. Hormone therapy, using tamoxifen citrate, may fight breast cancer by blocking the use of estrogen by the tumor cells. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, may fight breast cancer by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving tamoxifen citrate, anastrozole, letrozole, or exemestane is more effective with combination chemotherapy in treating patients with breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Tamoxifen Citrate</span>, <span class="go-doc-concept go-doc-intervention">Letrozole</span>, <span class="go-doc-concept go-doc-intervention">Anastrozole</span>, or <span class="go-doc-concept go-doc-intervention">Exemestane</span> With or Without <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> in Treating Patients With Invasive RxPONDER <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer
  • Official Title: A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients With 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer With Recurrence Score (RS) of 25 or Less. RxPONDER: A Clinical Trial Rx for Positive Node, Endocrine Responsive Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT01272037

    ORG ID: NCI-2011-02623

    NCI ID: NCI-2011-02623

    Trial Conditions

    Ductal Breast Carcinoma In Situ

    Estrogen Receptor and/or Progesterone Receptor Positive

    HER2/Neu Negative

    Invasive Breast Carcinoma

    Multicentric Breast Carcinoma

    Multifocal Breast Carcinoma

    Synchronous Bilateral Breast Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Anastrozole Arimidex, ICI D1033, ICI-D1033, ZD-1033 Arm I (chemotherapy and endocrine therapy), Arm II (endocrine therapy)
    Exemestane Aromasin, FCE-24304 Arm I (chemotherapy and endocrine therapy), Arm II (endocrine therapy)
    Letrozole CGS 20267, Femara Arm I (chemotherapy and endocrine therapy), Arm II (endocrine therapy)
    Systemic Chemotherapy Arm I (chemotherapy and endocrine therapy)
    Tamoxifen Citrate Apo-Tamox, Clonoxifen, Dignotamoxi, Ebefen, Emblon, Estroxyn, Fentamox, Gen-Tamoxifen, Genox, ICI 46,474, ICI-46474, Jenoxifen, Kessar, Ledertam, Lesporene, Nolgen, Noltam, Nolvadex, Nolvadex-D, Nourytam, Novo-Tamoxifen, Novofen, Noxitem, Oestrifen, Oncotam, PMS-Tamoxifen, Soltamox, TAM, Tamax, Tamaxin, Tamifen, Tamizam, Tamofen, Tamoxasta, Tamoxifeni Citras, Zemide Arm I (chemotherapy and endocrine therapy), Arm II (endocrine therapy)

    Trial Purpose

    This randomized phase III clinical trial studies how well tamoxifen citrate, anastrozole,
    letrozole, or exemestane with or without chemotherapy work in treating patients with breast
    cancer that has spread from where it began in the breast to surrounding normal tissue
    (invasive). Estrogen can cause the growth of breast cancer cells. Hormone therapy, using
    tamoxifen citrate, may fight breast cancer by blocking the use of estrogen by the tumor
    cells. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, may fight
    breast cancer by lowering the amount of estrogen the body makes. Drugs used in chemotherapy
    work in different ways to stop the growth of tumor cells, either by killing the cells, by
    stopping them from dividing, or by stopping them from spreading. It is not yet known whether
    giving tamoxifen citrate, anastrozole, letrozole, or exemestane is more effective with
    combination chemotherapy in treating patients with breast cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the effect of chemotherapy in patients with node positive breast cancer who
    do not have high recurrence scores (RS) by Oncotype DX.

    SECONDARY OBJECTIVES:

    I. To compare overall survival (OS), distant disease-free survival (DDFS) and local
    disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.

    II. To compare the toxicity across the treatment arms. III. To perform other assays or tests
    (in particular the prediction analysis of microarray [PAM50] risk of relapse score), as they
    are developed and validated that measure potential benefit of chemotherapy and compare them
    to Oncotype DX.

    IV. To determine the impact of management with Oncotype DX on patient-reported anxiety
    (co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after
    disclosure of test results, and during the randomized trial.

    V. To determine the impact of Oncotype DX on the initial management cost of node-positive,
    hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative
    breast cancer.

    VI. To compare patient-reported utilities (e.g., quality of life [QOL]) for those randomized
    to chemotherapy versus no chemotherapy.

    VII. Using modeling and DFS information from the trial, to estimate the cost-effectiveness
    of management with Oncotype DX vs usual care.

    VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and
    LDFI for patients randomized to chemotherapy versus no chemotherapy.

    IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on
    patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).

    X. To determine the impact of management with Oncotype DX on patient-reported decision
    conflict, perceptions regarding Oncotype DX testing, and survivor concerns prior to
    screening, after disclosure of test results, and during the randomized trial (secondary HRQL
    outcomes).

    OUTLINE: Patients are randomized to 1 of 2 treatment arms.

    ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or
    physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy
    comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or
    exemestane), or both for 5-10 years in the absence of disease progression or unacceptable
    toxicity.

    ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate,
    an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in
    the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up every 3 months for 1 year,
    every 6 months for 4 years, and then yearly for 15 years.

    Trial Arms

    Name Type Description Interventions
    Arm I (chemotherapy and endocrine therapy) Experimental Patients receive a protocol-approved chemotherapy regimen based on the patient and/or physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity. Anastrozole, Exemestane, Letrozole, Systemic Chemotherapy, Tamoxifen Citrate
    Arm II (endocrine therapy) Experimental Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity. Anastrozole, Exemestane, Letrozole, Tamoxifen Citrate

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes)
    invasive breast carcinoma with positive estrogen and/or progesterone receptor status,
    and negative HER-2 status; estrogen and progesterone receptor positivity must be
    assessed according to American Society of Clinical Oncology (ASCO)/College of
    American Pathologists (CAP) guidelines as either estrogen receptor (ER) or
    progesterone receptor (PR) >= 1% positive nuclear staining; HER-2 test result
    negativity must be assessed as per ASCO/CAP 2013 guidelines using
    immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if
    a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0
    or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number
    < 4.0 signals per cell by single probe or HER-2/CEP ration < 2.0 with an average copy
    number < 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene
    amplification (ISH) must be performed and the ISH must be negative; ISH is not
    required if IHC is 0 or 1+; HER-2 equivocal is not eligible

    - Patients with multifocal, multicentric and synchronous bilateral breast cancers are
    allowed

    - Multifocal disease is defined as more than one invasive cancer < 2 cm from the
    largest lesion within the same breast quadrant; (NOTE: the Oncotype DX testing
    must be completed on the largest lesion)

    - Multicentric disease is defined as more than one invasive cancer >= 2 cm from
    the largest lesion within the same breast quadrant or more than one lesion in
    different quadrants (NOTE: Oncotype DX testing should be completed on all tumors
    and the determination for eligibility should be made on the highest recurrence
    score)

    - Synchronous bilateral disease is defined as invasive breast cancer with positive
    lymph nodes (axillary or intramammary) in at least one breast, diagnosed within
    30 days of each other; (NOTE: The Oncotype DX testing should be completed on
    both tumors and the tumor with the highest recurrence score should be used)

    - Patients will have undergone axillary staging by sentinel node biopsy or axillary
    lymph nodes dissection (ALND); patients must have at least one, but no more than
    three known positive lymph nodes (pN1a, pN1b or pN1c); patients with micrometastases
    as the only nodal involvement (pN1mi) are not eligible; patients with positive
    sentinel node are not required to undergo full axillary lymph node dissection; this
    is at the discretion of the treating physician; axillary node evaluation is to be
    performed per the standard of care at each institution

    - Patients must not have inflammatory breast cancer and must not have metastatic
    disease; patients with a prior diagnosis of contralateral ductal carcinoma in situ
    (DCIS) are eligible if they underwent a mastectomy or lumpectomy with whole breast
    radiation; prior partial breast irradiation, including brachytherapy, is not allowed;
    patients with a prior diagnosis of ipsilateral DCIS or invasive breast cancer who
    received radiation to that breast are not eligible

    - Patients must have had either breast-conserving surgery with planned radiation
    therapy or total mastectomy (with or without planned postmastectomy radiation);
    patients must have clear margins from both invasive breast cancer and DCIS (as per
    local institutional guidelines); lobular carcinoma in situ (LCIS) at the margins is
    allowed

    - Registration of patients who have not yet undergone Oncotype DX screening must occur
    no later than 56 days after definitive surgery; (for all patients, Step 2
    Registration must occur within 84 days after definitive surgery); if the Oncotype DX
    Breast Cancer Assay has not been performed, patients must be willing to submit tissue
    samples for testing to determine the Recurrence Score value; a representative block
    or unstained sections from the representative block are sent directly to Genomic
    Health for Oncotype DX Breast Cancer Assay which will be performed according to the
    standard commercial process

    - If the Oncotype DX Recurrence Score is already known and is 25 or less, the
    patient must be registered to Step 2 immediately following Step 1 registration;
    if the Oncotype DX Recurrence Score is already known and is greater than 25, the
    patient is ineligible

    - Patients must have a complete history and physical examination within 28 days prior
    to registration

    - Patients must have a performance status of 0-2 by Zubrod criteria

    - Patients must be able to receive taxane and/or anthracycline based chemotherapy

    - Patients must not have begun chemotherapy or endocrine therapy for their breast
    cancer prior to registration

    - Patients must not require concurrent chronic treatment with systemic steroids
    (inhaled steroids are allowed) or other immunosuppressive agents

    - Patients must not have received an aromatase inhibitor (AI) or a selective estrogen
    receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to
    registration

    - Patients must not be pregnant or nursing; women of reproductive potential must have
    agreed to use an effective contraceptive method; a woman is considered to be of
    "reproductive potential" if she has had menses at any time in the preceding 12
    consecutive months; in addition to routine contraceptive methods, "effective
    contraception" also includes heterosexual celibacy and surgery intended to prevent
    pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
    bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
    previously celibate patient chooses to become heterosexually active during the time
    period for use of contraceptive measures outlined in the protocol, he/she is
    responsible for beginning contraceptive measures

    - No other prior malignancy is allowed except for adequately treated basal cell (or
    squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the
    patient has been disease-free for 5 years

    - The Quality of Life and Economic Substudy is permanently closed to accrual effective
    12/1/12; patients who consented to QOL prior to 12/1/12 should continue to complete
    QOL forms per their expectation report; patients who are able to complete a
    questionnaire in English must be offered the opportunity to participate in the
    Quality of Life and Economic Substudy; (The Quality of Life and Economic Substudy is
    available to U.S. INSTITUTIONS ONLY); patients who are not able to complete a
    questionnaire in English are registered to S1007 without participating in the Quality
    of Life and Economic Substudy

    - Patients who consent to participate in the Quality of Life and Economic Substudy
    and who do not yet know the results of their Oncotype DX screening must agree to
    complete the S1007 Health-Related Quality of Life Questionnaire: Enrollment
    between 14 days prior to and 7 days after Step 1 Registration

    - Patients who consent to participate in the Quality of Life and Economic Substudy
    and who do already know their Oncotype DX Recurrence Score (and it is 25 or
    less) will proceed to Step 2 Registration without completing the S1007
    Health-Related Quality of Life Questionnaire Enrollment Form (but will complete
    the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form)

    - Patients or their legally authorized representative must be informed of the
    investigational nature of this study and must sign and give written informed consent
    in accordance with institutional and federal guidelines; for Step 1 registration of
    patients who have not yet submitted specimens for the Oncotype DX Breast Cancer
    Assay, the appropriate consent form is the Step 1 Consent Form; for both Step 1 and
    Step 2 registration of patients whose Recurrence Score is already known and is 25 or
    less, the appropriate consent form is the Step 2 Consent Form

    - As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
    treating institution's identity is provided in order to ensure that the current
    (within 365 days) date of institutional review board approval for this study has been
    entered in the system

    - STEP 2 REGISTRATION

    - Recurrence score (RS) by Oncotype DX must be =< 25

    - Step 2 Registration must take place within 84 days after definitive surgery; patients
    must not have begun chemotherapy or endocrine therapy for their breast cancer prior
    to randomization

    - Patients randomized to either arm may also co-enroll in phase III trials that compare
    local therapies, or compare systemic therapies (such as chemotherapy, if randomized
    to Arm I of S1007)

    - The Quality of Life and Economic Substudy is permanently closed to accrual effective
    12/1/12; patients at U.S. INSTITUTIONS who consent to participate in the Quality of
    Life and Economic Substudy must agree to complete the S1007 Health-Related Quality of
    Life Questionnaire: Randomized Study Form after Recurrence Score results and
    randomized treatment status are known but before treatment has been initiated

    - Patients or their legally authorized representative must be informed of the
    investigational nature of this study and must sign and give written informed consent
    in accordance with institutional and federal guidelines; for all patients the
    appropriate consent form for this registration is the Step 2 Consent

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    RS, as measured by Oncotype DX

    Secondary Outcome Measures

    DDFS

    Local disease-free interval

    OS

    Toxicities using standard National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0

    Trial Keywords