Program for the Assessment of Clinical Cancer Tests (PACCT-1): Trial Assigning Individualized Options for Treatment:The TAILORx Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 10,273
- 试验地点
- 2,312
- 主要终点
- 5-year Disease-free Survival
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES:
I. 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:
I. 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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/mm^3
- •Platelets >= 100,000/mm^3
- •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
排除标准
- 未提供
研究组 & 干预措施
Group 2, Arm I (experimental)
Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.
干预措施: Exemestane (Drug)
Group 1 (Oncotype DX recurrence score =< 10)
Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.
干预措施: Exemestane (Drug)
Group 2, Arm I (experimental)
Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.
干预措施: Quality-of-Life Assessment (Other)
Group 3 (Oncotype DX recurrence score >= 26)
Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.
干预措施: Quality-of-Life Assessment (Other)
Group 2, Arm I (experimental)
Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.
干预措施: Anastrozole (Drug)
Group 3 (Oncotype DX recurrence score >= 26)
Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.
干预措施: Radiation Therapy (Radiation)
Group 1 (Oncotype DX recurrence score =< 10)
Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.
干预措施: Laboratory Biomarker Analysis (Other)
Group 2, Arm I (experimental)
Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.
干预措施: Laboratory Biomarker Analysis (Other)
Group 2, 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.
干预措施: Laboratory Biomarker Analysis (Other)
Group 2, 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.
干预措施: Radiation Therapy (Radiation)
Group 3 (Oncotype DX recurrence score >= 26)
Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.
干预措施: Laboratory Biomarker Analysis (Other)
Group 3 (Oncotype DX recurrence score >= 26)
Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.
干预措施: Tamoxifen Citrate (Drug)
Group 2, Arm I (experimental)
Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.
干预措施: Tamoxifen Citrate (Drug)
Group 1 (Oncotype DX recurrence score =< 10)
Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.
干预措施: Tamoxifen Citrate (Drug)
Group 2, 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.
干预措施: Tamoxifen Citrate (Drug)
Group 2, 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.
干预措施: Anastrozole (Drug)
Group 2, Arm I (experimental)
Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.
干预措施: Letrozole (Drug)
Group 1 (Oncotype DX recurrence score =< 10)
Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.
干预措施: Quality-of-Life Assessment (Other)
Group 1 (Oncotype DX recurrence score =< 10)
Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.
干预措施: Radiation Therapy (Radiation)
Group 2, 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.
干预措施: Quality-of-Life Assessment (Other)
Group 1 (Oncotype DX recurrence score =< 10)
Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.
干预措施: Anastrozole (Drug)
Group 1 (Oncotype DX recurrence score =< 10)
Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.
干预措施: Letrozole (Drug)
Group 2, 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.
干预措施: Exemestane (Drug)
Group 2, 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.
干预措施: Letrozole (Drug)
Group 3 (Oncotype DX recurrence score >= 26)
Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.
干预措施: Anastrozole (Drug)
Group 3 (Oncotype DX recurrence score >= 26)
Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.
干预措施: Letrozole (Drug)
Group 3 (Oncotype DX recurrence score >= 26)
Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.
干预措施: Exemestane (Drug)
结局指标
主要结局
5-year Disease-free Survival
时间窗: Assessed every 6 months within 5 years from registration and then annually up to 20 years, DFS rate estimated at 5 years
Disease-free survival (DFS) is defined to be time from randomization to first event, where the first event is any of ipsilateral breast tumor recurrence, local recurrence, regional recurrence, distant recurrence, contralateral second primary invasive cancer, second primary non-breast invasive cancer (excluding non-melanoma skin cancers), or death without evidence of recurrence. The distribution of DFS (eg, 5-year DFS rate) is estimated using Kaplan-Meier method, and compared between the two randomized arms (arm B vs. arm C) using stratified log rank test and stratified Cox proportional hazard model.
次要结局
- 5-year Disease-free Survival by Age and Recurrence Score Groups(Assessed every 6 months within 5 years from registration and then annually up to 20 years, DFS rate estimated at 5 years)
- 5-year Overall Survival(Assessed every 6 months within 5 years from registration and then annually up to 20 years, OS rate estimated at 5 years)
- 5-year Recurrence-free Interval(Assessed every 6 months within 5 years from registration and then annually up to 20 years, RFS rate estimated at 5 years)
- To Compare the Outcomes Projected at 10 Years by Adjuvant! With Those Made by the Genomic Health Oncotype DX Test(Assessed at 10 years after study entry)
- 5-year Distant Recurrence-free Interval(Assessed every 6 months within 5 years from registration and then annually up to 20 years, DRFI rate estimated at 5 years)
- 5-year Disease-free Survival by Individual RS Gene Groups(Assessed every 6 months within 5 years from registration and then annually up to 20 years)