A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients With Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- NSABP Foundation Inc
- Enrollment
- 1,636
- Locations
- 514
- Primary Endpoint
- IBC-RFI
Study Overview
Brief Summary
This randomized phase III trial studies standard or comprehensive radiation therapy in treating patients with early-stage breast cancer who have undergone surgery. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether comprehensive radiation therapy is more effective than standard radiation therapy in treating patients with breast cancer
Detailed Description
PRIMARY OBJECTIVES:
To evaluate whether the addition of chest wall + regional nodal radiation therapy (XRT) after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rate of events for invasive breast cancer recurrence-free interval (IBC-RFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly prolong overall survival (OS) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.
II. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rates of events for local-regional recurrence-free interval (LRRFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
- •The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patient must have clinically T1-3, N1 breast cancer at the time of diagnosis (before neoadjuvant therapy); clinical axillary nodal involvement can be assessed by palpation, ultrasound, CT scan, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, or PET/CT scan
- •Patient must have had pathologic confirmation of axillary nodal involvement at presentation (before neoadjuvant therapy) based on either a positive fine needle aspirate (FNA) (demonstrating malignant cells) or positive core needle biopsy (demonstrating invasive adenocarcinoma); the FNA or core needle biopsy can be performed either by palpation or by image guidance; documentation of axillary nodal positivity by sentinel node biopsy (before neoadjuvant therapy) is not permitted
- •Patients must have had estrogen receptor (ER) analysis performed on the primary breast tumor before neoadjuvant therapy according to current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing; if negative for ER, assessment of progesterone receptor (PgR) must also be performed according to current ASCO/CAP guideline recommendations for hormone receptor testing (http://www.asco.org)
- •Patients must have had HER2 testing performed on the primary breast tumor before neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations for human epidermal growth factor receptor 2 testing in Breast Cancer (http://www.asco.org); patients who have a primary tumor that is either HER2-positive or HER2-negative are eligible
- •Patient must have completed a minimum of 8 weeks of standard neoadjuvant chemotherapy consisting of an anthracycline and/or taxane-based regimen
- •For patients who receive adjuvant chemotherapy after surgery, a maximum of 12 weeks of intended chemotherapy may be administered but must be completed before randomization; (if treatment delays occur, chemotherapy must be completed within 14 weeks); the dose and schedule of the adjuvant chemotherapy are at the investigator's discretion; Note: It is preferred that all intended chemotherapy be administered in the neoadjuvant setting
- •Patients with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen), unless medically contraindicated
- •At the time of definitive surgery, all removed axillary nodes must be histologically free from cancer; acceptable procedures for assessment of axillary nodal status at the time of surgery include:
- •Axillary node dissection
- •Sentinel node biopsy alone or
- •Sentinel node biopsy followed by axillary node dissection
- •Note: Patients are eligible whether there is residual invasive carcinoma in the surgical breast specimen or whether there is evidence of pathologic complete response; patients who are found to be pathologically node-positive at the time of surgery, based on sentinel node biopsy alone, are candidates for A011202, a study developed by the Alliance in Oncology, an NCI Cooperative Group; if A011202 is open at the investigator's institution, patients should be approached about participating in the A011202 study
- •Patients with pathologic staging of ypN0(i+) or ypN0(mol+) are eligible (Note: Postneoadjuvant therapy is designated with a "yp" prefix.)
- •Patient who have undergone either a total mastectomy or a lumpectomy are eligible
- •For patients who undergo lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS as determined by the local pathologist; additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible; (patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection)
- •For patients who undergo mastectomy, the margins must be histologically free of residual (microscopic or gross) tumor
- •The interval between the last surgery for breast cancer (including re-excision of margins) and randomization must be no more than 70 days; also, if adjuvant chemotherapy was administered, the interval between the last chemotherapy treatment and randomization must be no more than 70 days
- •The patient must have recovered from surgery with the incision completely healed and no signs of infection
- •If adjuvant chemotherapy was administered, chemotherapy-related toxicity that may interfere with delivery of radiation therapy should have resolved
Exclusion Criteria
- •Definitive clinical or radiologic evidence of metastatic disease
- •T4 tumors including inflammatory breast cancer
- •Documentation of axillary nodal positivity before neoadjuvant therapy by sentinel node biopsy alone
- •N2 or N3 disease detected clinically or by imaging
- •Patients with histologically positive axillary nodes post neoadjuvant therapy
- •Patients with microscopic positive margins after definitive surgery
- •Synchronous or previous contralateral invasive breast cancer or DCIS; (patients with synchronous and/or previous contralateral LCIS are eligible)
- •Any prior history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy; (patients with synchronous or previous ipsilateral LCIS are eligible)
- •History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization
- •Any radiation therapy for the currently diagnosed breast cancer prior to randomization
- •Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy; patients are eligible if these medications are discontinued prior to randomization
- •Prior breast or thoracic radiation therapy (RT) for any condition
- •Active collagen vascular disease, specifically dermatomyositis with a creatinine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma
- •Pregnancy or lactation at the time of study entry; (Note: Pregnancy testing must be performed within 2 weeks prior to randomization according to institutional standards for women of childbearing potential)
- •Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
- •Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
Arms & Interventions
Group 1A Lumpectomy: no regional nodal XRT with WBI
Lumpectomy patients undergo whole breast radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.
Intervention: WBI (Radiation)
Group 1B Mastectomy: No regional nodal or chestwall XRT
Mastectomy patients do not undergo radiation therapy.
Group 2A lumpectomy: Regional nodal XRT with WBI
Lumpectomy patients undergo regional nodal radiation therapy with whole breast radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.
Intervention: regional nodal XRT (Radiation)
Group 2A lumpectomy: Regional nodal XRT with WBI
Lumpectomy patients undergo regional nodal radiation therapy with whole breast radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.
Intervention: WBI (Radiation)
Group 2B Mastectomy: Regional nodal XRT and chestwall XRT
Mastectomy patients undergo regional nodal radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks.
Intervention: regional nodal XRT (Radiation)
Group 2B Mastectomy: Regional nodal XRT and chestwall XRT
Mastectomy patients undergo regional nodal radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks.
Intervention: chestwall XRT (Radiation)
Outcomes
Primary Outcomes
IBC-RFI
Time Frame: Time from randomization until invasive local, regional, or distant recurrence, or death from breast cancer, assessed up to 10 years
Secondary Outcomes
- Effect of radiation therapy on cosmetic outcome in mastectomy and lumpectomy patients as assessed by quality of life questionnaire(Assessed prior to randomization, 3 months or at end of RT, and 6, 12, and 24 months from randomization)
- Frequencies of adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0(Up to 30 days after completion of study treatment)
- Time to SPC(Time from randomization to the development of a second primary invasive cancer of any site excluding squamous and basal cell carcinoma of the skin, assessed up to 10 years)
- LRRFI(Time from randomization to recurrence of primary cancer w/in breast or lymph nodes in ipsilateral axilla, infraclavicular fossa, or ipsilateral internal mammary chain w/out evidence distant disease, or death due to breast cancer, assessed up to 10 years)
- DRFI(Time from randomization to the development of tumor in all areas beyond local or regional limits, or death due to breast cancer, assessed up to 10 years)
- DFS-DCIS(Time from randomization to local recurrence post-mastectomy/in ipsilateral breast post-lumpectomy, regional/distant recurrence, contralateral disease, second primary cancer, or death from any cause prior to recurrence or SPC, assessed up to 10 years)
- Molecular predictors of recurrence(Tissue samples collected within 90 days after randomization)
- OS(Time from randomization to death from any cause, assessed up to 10 years)