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Summary

for females ages 18–75 (full criteria)
at Fresno, California and other locations
study started

Description

Summary

This randomized phase III trial studies the best individual therapy for women who have node-negative, estrogen-receptor positive breast cancer by using a special test (Oncotype DX), and whether hormone therapy alone or hormone therapy together with combination chemotherapy is better for women who have an Oncotype DX recurrence score of 11-25. Estrogen can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by blocking the use of estrogen by the tumor cells or 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. Giving hormone therapy together with more than one chemotherapy drug (combination chemotherapy) has been shown to reduce the chance of breast cancer recurrence, but the benefit of adding chemotherapy to hormone therapy for women with node-negative, estrogen-receptor positive breast cancer is small. New tests may provide information about which patients are more likely to benefit from chemotherapy.

Official Title

Program for the Assessment of Clinical Cancer Tests (PACCT-1): Trial Assigning Individualized Options for Treatment:The TAILORx Trial

Details

PRIMARY OBJECTIVES:

  1. To determine whether adjuvant hormonal therapy is not inferior to adjuvant chemohormonal in women whose tumors meet established clinical guidelines for adjuvant chemotherapy and fall in the "primary study group" category (Oncotype DX Recurrence Score 11-25).

II. To create a tissue and specimen bank for patients enrolled in this trial, including formalin fixed paraffin embedded tumor specimens, tissue microarrays, plasma, and deoxyribonucleic acid (DNA) obtained from peripheral blood.

SECONDARY OBJECTIVES:

  1. To determine whether adjuvant hormonal therapy is sufficient treatment (i.e. 10 year distant disease-free survival of at least 95%) for women whose tumors meet established clinical guidelines for adjuvant chemotherapy and who fall into the "Secondary Study Group-1" category (Oncotype DX Recurrence Score =< 10).

II. To compare the outcomes projected at 10 years by Adjuvant (with outcomes projected using classical pathologic information including tumor size, hormone receptor status, and histologic grade) with those made by the Genomic Health Oncotype DX test. Classical pathologic information and outcome results will also be used to create and refine models that would use classical information instead of or in combination with genomic tests.

III. To estimate failure rates as a function of recurrence score (RS) separately in the chemotherapy (arms C, D) and no chemotherapy (arms A, B) groups. The purpose of the analysis is to develop more precise estimates of the relationship between recurrence score and chemotherapy treatment effect, if any, at the upper range of the RS 11 - 25 group.

IV. To determine the prognostic significance of the Oncotype DX recurrence score and of the individual RS gene groups (proliferation gene group, human epidermal growth factor receptor [HER]2 gene group, estrogen receptor [ER] gene group, invasion gene group, and other genes).

TERTIARY OBJECTIVES:

  1. To evaluate the effects of chemotherapy and hormonal therapy vs hormonal therapy alone on perceived cognitive impairment, fatigue, fear of recurrence among pre-menopausal patients, endocrine symptoms and sexual dysfunction, and overall health-related quality of life (HRQL).

II. To determine whether perceived cognitive impairment, fatigue, fear of recurrence, endocrine symptoms, and overall HRQL are similar for patients receiving chemotherapy plus hormonal therapy in secondary study group 2 as for those in the primary study group (arm D vs C).

III. To determine whether perceived cognitive impairment, fatigue, fear of recurrence, endocrine symptoms, and overall HRQL are similar for patients receiving hormonal therapy alone in secondary study group 1 as for those in the primary study group (arms A vs B).

IV. To determine whether age will be inversely associated with a fear of recurrence, independent of treatment assignment.

  1. Among participants receiving hormonal treatment alone on arm A and arm B, to determine whether Oncotype DX Recurrence score will be inversely correlated with fear of recurrence.

VI. To create a biospecimen repository including plasma, serum and CellSearch cassettes containing circulating tumor cells (CTC) for evaluating determinants of late relapse, including candidate biomarkers reflecting occult tumor burden (e.g., CTCs and plasma tumor DNA) and host factors (e.g., estrogen, insulin growth factor-[IGF] axis, inflammation, etc).

VII. To create a biorepository of metastatic tumor samples in patients who have had a late relapse.

VIII. To determine body mass index (BMI) and comorbidity burden in patients with operable breast cancer five or more years after diagnosis.

IX. To determine whether there is a relationship between late relapse and BMI at diagnosis and at 5 years after diagnosis, and whether BMI-associated inflammatory and/or metabolic biomarkers are associated with early and late recurrence.

OUTLINE: This is a partially randomized study. Patients are assigned to 1 of 3 treatment groups.

GROUP 1 (SECONDARY STUDY GROUP 1; ONCOTYPE DX RECURRENCE SCORE [ODRS] =< 10): Patients receive standard hormonal therapy (e.g., tamoxifen alone orally (PO), aromatase inhibitor [e.g., anastrozole, letrozole, or exemestane] alone PO, or tamoxifen PO followed by aromatase inhibitor PO) at the discretion of the treating physician for 5 or 10 years.

GROUP 2 (PRIMARY STUDY GROUP; ODRS 11-25): Patients are randomized to receive either hormonal therapy alone or combination chemotherapy and hormonal therapy.

ARM I (EXPERIMENTAL): Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.

ARM II (STANDARD): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.

GROUP 3 (SECONDARY STUDY GROUP 2; ODRS >= 26): Patients receive combination chemotherapy as in Group 2, Arm II followed by hormonal therapy as in Group 1.

Patients in all groups who have had breast-conservation surgery are also treated with radiotherapy. Radiotherapy should begin within 4 weeks of registration for patients receiving hormonal therapy alone or within 8 weeks after completion of chemotherapy. Patients participating in National Surgical Adjuvant Breast and Bowel Project (NSABP) and/or Radiation Therapy Oncology Group (RTOG) partial irradiation trial(s) may receive partial breast radiation.

After completion of study treatment, patients are followed up every 3-6 months for 5 years and then annually for 15 years.

Keywords

Breast Adenocarcinoma Estrogen Receptor and/or Progesterone Receptor Positive HER2/Neu Negative Stage IA Breast Cancer AJCC v7 Stage IB Breast Cancer AJCC v7 Stage IIA Breast Cancer AJCC v6 and v7 Stage IIB Breast Cancer AJCC v6 and v7 Stage IIIB Breast Cancer AJCC v7 Breast Neoplasms Adenocarcinoma Hormones Letrozole Exemestane Anastrozole Tamoxifen

Eligibility

For females ages 18–75

Inclusion Criteria:

  • Patients with operable histologically confirmed adenocarcinoma of the female breast who have completed primary surgical treatment and meet the following criteria:
  • ER and/or progesterone receptor (PR)-positive: Estrogen and/or progesterone receptor positive disease (as defined by local pathology laboratory)
  • Negative axillary nodes: As assessed by a sentinel lymph node biopsy, an axillary dissection, or both, and as defined by the Sixth Edition of the American Joint Committee on Cancer (AJCC) staging criteria
  • Tumor size 1.1-5.0 cm (or 5 mm-1.0 cm plus unfavorable histological features):
  • Unfavorable features defined as intermediate or poor nuclear and/or histologic grade, or lymphovascular invasion
  • NOTE: Definition of tumor size: The tumor size used for determination of eligibility is the pathologic tumor size, which is usually determined by the size of the tumor as measured by inspection of the gross specimen; if the tumor size is measured microscopically and the tumor includes ductal carcinoma in-situ, the measurement should include only the invasive component of the tumor
  • The tumor must be human epidermal growth factor receptor 2 (Her2)/neu negative by either fluorescent in-situ hybridization (FISH) or immunohistochemistry (e.g. 0 or 1+ by DAKO Herceptest)
  • The patient and physician must be agreeable to initiate standard chemotherapy and hormonal therapy as adjuvant therapy
  • A tissue specimen from the primary breast cancer has been located and is ready to be shipped to the appropriate laboratory after consent is obtained and within 3 days following pre-registration; NOTE: For determination of the Oncotype Recurrence Score,tissue must be shipped to Genomic Health; if the Oncotype DX Recurrence Score was previously performed by Genomic Health (prior to pre-registration), tissue must be submitted to the Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) Central Biorepository and Pathology Facility upon randomization
  • Leukocyte count >= 3500/mm3

  • Platelets >= 100,000/mm3

  • Serum creatinine =< 1.5 mg/dL
  • Serum aspartate transaminase (AST) that is =< 3-fold the upper institutional limits of normal
  • Patients must be disease-free of prior invasive malignancies for >= 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; patients with a previous ipsilateral or contralateral invasive breast cancer, or with bilateral synchronous cancers, are not eligible;patients with previous ipsilateral or contralateral ductal in situ carcinoma (DCIS)are not eligible
  • Prior treatment
  • Mandatory prior surgery criteria:
  • Patient must pre-register within 84 days from the final surgical procedure required to adequately treat the primary tumor (please note that if margins are not clear and a resection has to be conducted after pre-registration but before randomization, the patient will be deemed to be within the 84 day window allowed by protocol and therefore eligible)
  • All tumors should be removed by either a mastectomy or local excision plus an acceptable axillary procedure (i.e., sentinel lymph node biopsy, axillary dissection, or both); there must be adequate (at least 1 mm if margin width specified) tumor-free margins of resection (for invasive and ductal carcinoma in-situ) in order for the patients to be eligible; patients with lobular carcinoma in-situ involving the resection margins are eligible
  • Criteria re: other prior treatments:
  • No prior chemotherapy for this malignancy
  • No prior radiation therapy for this malignancy; this includes no prior MammoSite Brachytherapy radiation therapy (RT)
  • Hormonal therapy: Patients who develop breast cancer while receiving a selective estrogen-receptor modulator (SERM; e.g., tamoxifen, toremifene,raloxifene) or an aromatase inhibitor (e.g., anastrazole, letrozole,exemestane) for breast cancer prevention or a SERM for other indications(e.g., raloxifene for osteoporosis) are not eligible; however, patients may have received up to 8 weeks of a SERM or aromatase inhibitor for this malignancy and still be eligible for study entry
  • Patients must have an anticipated life expectancy of at least 10 years
  • Patients with the following medical conditions should not be enrolled on the study:
  • Chronic obstructive pulmonary disease requiring treatment
  • Chronic liver disease (e.g., cirrhosis, chronic active hepatitis)
  • Previous history of a cerebrovascular accident
  • History of congestive heart failure or other cardiac disease that would represent a contraindication to the use of an anthracycline (e.g., doxorubicin or epirubicin)
  • Chronic psychiatric condition or other condition that would impair compliance with the treatment regimen
  • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to pre-registration to rule out pregnancy
  • Women of childbearing potential must be strongly advised to utilize an accepted and effective form of non-hormonal contraception (e.g. intrauterine device,condoms, diaphragm, abstinence)
  • Patients must not have previously had the Oncotype DX Assay performed, with the exception of patients who have had the assay performed and have a recurrence score of 11-25

Locations

  • California Cancer Center - North Fresno
    Fresno, California, 93720, United States
  • Cancer Care Associates of Fresno Medical Group Inc
    Fresno, California, 93720, United States
  • Zuckerberg San Francisco General Hospital
    San Francisco, California, 94110, United States
  • California Pacific Medical Center-Pacific Campus
    San Francisco, California, 94115, United States
  • Kaiser Permanente-San Francisco
    San Francisco, California, 94115, United States
  • Kaiser Permanente-South San Francisco
    South San Francisco, California, 94080, United States
  • Bay Area Breast Surgeons Inc
    Emeryville, California, 94608, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, United States
  • Bay Area Tumor Institute
    Oakland, California, 94609, United States
  • Hematology and Oncology Associates-Oakland
    Oakland, California, 94609, United States
  • Tom K Lee Inc
    Oakland, California, 94609, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, 94704, United States
  • Marin General Hospital
    Greenbrae, California, 94904, United States
  • Highland General Hospital
    Oakland, California, 94602, United States
  • Kaiser Permanente-Richmond
    Richmond, California, 94801, United States
  • Mills-Peninsula Medical Center
    Burlingame, California, 94010, United States
  • Kaiser Permanente-Oakland
    Oakland, California, 94611, United States
  • Doctors Medical Center- JC Robinson Regional Cancer Center
    San Pablo, California, 94806, United States
  • Kaiser Permanente San Leandro
    San Leandro, California, 94577, United States
  • Kaiser Permanente-San Rafael
    San Rafael, California, 94903, United States
  • East Bay Radiation Oncology Center
    Castro Valley, California, 94546, United States
  • Eden Hospital Medical Center
    Castro Valley, California, 94546, United States
  • Valley Medical Oncology Consultants-Castro Valley
    Castro Valley, California, 94546, United States
  • Saint Rose Hospital
    Hayward, California, 94545, United States
  • Contra Costa Regional Medical Center
    Martinez, California, 94553-3156, United States
  • Kaiser Permanente-Redwood City
    Redwood City, California, 94063, United States
  • Kaiser Permanente-Walnut Creek
    Walnut Creek, California, 94596, United States
  • Sutter Cancer Research Consortium
    Novato, California, 94945, United States
  • John Muir Medical Center-Walnut Creek
    Walnut Creek, California, 94598, United States
  • John Muir Medical Center-Concord Campus
    Concord, California, 94520, United States
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California, 94304, United States
  • Kaiser Permanente-Vallejo
    Vallejo, California, 94589, United States
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California, 94589, United States
  • Kaiser Permanente-Fremont
    Fremont, California, 94538, United States
  • Valley Medical Oncology Consultants-Fremont
    Fremont, California, 94538, United States
  • Washington Hospital
    Fremont, California, 94538, United States
  • Valley Care Health System - Pleasanton
    Pleasanton, California, 94588, United States
  • Valley Medical Oncology Consultants
    Pleasanton, California, 94588, United States
  • Kaiser Permanente Medical Center - Santa Clara
    Santa Clara, California, 95051, United States
  • Santa Rosa Memorial Hospital
    Santa Rosa, California, 95405, United States
  • Northbay Cancer Center
    Vacaville, California, 95687, United States
  • Kaiser Permanente Medical Center-Vacaville
    Vacaville, California, 95688, United States
  • Kaiser Permanente-Santa Teresa-San Jose
    San Jose, California, 95119, United States
  • Kaiser Permanente-Santa Rosa
    Santa Rosa, California, 95403, United States
  • Kaiser Permanente-Stockton
    Stockton, California, 95210, United States
  • Kaiser Permanente-South Sacramento
    Sacramento, California, 95823, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, United States
  • Sutter Medical Center Sacramento
    Sacramento, California, 95816, United States
  • Mercy General Hospital
    Sacramento, California, 95819, United States
  • Emanuel Medical Center
    Turlock, California, 95382, United States
  • Kaiser Permanente - Sacramento
    Sacramento, California, 95825, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Salinas Valley Memorial
    Salinas, California, 93901, United States
  • Community Hospital of Monterey Peninsula
    Monterey, California, 93940, United States
  • Kaiser Permanente-Roseville
    Roseville, California, 95661, United States
  • Sutter Roseville Medical Center
    Roseville, California, 95661, United States
  • Fremont - Rideout Cancer Center
    Marysville, California, 95901, United States
  • PCR Oncology
    Pismo Beach, California, 93449, United States
  • Santa Barbara Hematology Oncology Group Inc-Solvang
    Solvang, California, 93463, United States
  • Ray, Margaret, Savage. M.D. (UIA Investigator)
    Santa Barbara, California, 93111, United States
  • Cancer Center of Santa Barbara
    Santa Barbara, California, 93105, United States
  • Sansum Clinic Inc
    Santa Barbara, California, 93105, United States
  • Santa Barbara Hematology Oncology Group Inc-Santa Barbara
    Santa Barbara, California, 93105, United States
  • Carson-Tahoe Specialty Medical Center
    Carson City, Nevada, 89703, United States
  • Olive View-University of California Los Angeles Medical Center
    Sylmar, California, 91342, United States
  • Providence Holy Cross Medical Center
    Mission Hills, California, 91346-9600, United States
  • Northridge Hospital Medical Center
    Northridge, California, 91325, United States
  • Renown Regional Medical Center
    Reno, Nevada, 89502, United States
  • Mercy Regional Cancer Center
    Redding, California, 96001, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, United States
  • Glendale Memorial Hospital and Health Center
    Glendale, California, 91204, United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California, 90033, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California, 91010, United States
  • Presbyterian Intercommunity Hospital
    Whittier, California, 90602, United States
  • Pomona Valley Hospital Medical Center
    Pomona, California, 91767, United States
  • UCLA / Jonsson Comprehensive Cancer Center
    Los Angeles, California, 90095, United States
  • Long Beach Memorial Medical Center-Todd Cancer Institute
    Long Beach, California, 90806, United States
  • Saint Jude Medical Center
    Fullerton, California, 92835, United States
  • Saint Joseph Hospital - Orange
    Orange, California, 92868, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California, 92868, United States
  • Loma Linda University Medical Center
    Loma Linda, California, 92354, United States
  • University Medical Center of Southern Nevada
    Las Vegas, Nevada, 89102, United States
  • Nevada Cancer Research Foundation CCOP
    Las Vegas, Nevada, 89106, United States
  • Desert Regional Medical Center
    Palm Springs, California, 92262, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT00310180
Phase
Phase 3
Lead Scientist
Study Type
Interventional
Last Updated
October 16, 2017