Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Ph 3 Post-Mast CW & RXRT & Post-Lump RXRT in PA Nodes before NCT who Convert to PNA Nodes after NCT

Protocol: RTOG-1304

Full Title

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

Study Objective

PRIMARY OBJECTIVES:

I. 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.

III. 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 rate of events for distant recurrence-free interval (DRFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.

IV. To compare the rates of disease-free survival (DFS)-ductal carcinoma in situ (DCIS) by treatment arm.

V. To compare the rates of second primary cancer by treatment arm.

VI. To compare the effect of adding XRT on the cosmetic outcomes in mastectomy patients who have had reconstruction.

VII. To compare the effect of adding XRT on quality of life including arm problems, lymphedema, pain, and fatigue.

VIII. To evaluate the toxicity associated with each of the radiation therapy regimens.

IX. To determine whether computed tomography (CT)-based conformal methods (intensity-modulated radiation therapy [IMRT] and 3-dimensional conformal radiation therapy [3DCRT]) for chest-wall + regional nodal XRT post mastectomy and regional nodal XRT with breast XRT following breast conserving surgery are feasible in a multi-institutional setting and whether dose-volume analyses can be established to assess treatment adequacy and to develop normal tissue complication probabilities (NTCP) for the likelihood of toxicity.

X. To compare the effect of XRT in patients receiving mastectomy and in patients receiving lumpectomy.

XI. To examine the role of proliferation measures as a prognosticator for patients with residual disease after neoadjuvant chemotherapy.

XII. To develop predictors of the degree of reduction in local regional recurrence (LRR).

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

ARM I: Patients are assigned to 1 of 2 treatment groups.

GROUP IA: Lumpectomy patients undergo whole breast radiation therapy using IMRT or 3D-CRT once daily (QD) 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.

GROUP IB: Mastectomy patients do not undergo radiation therapy.

ARM II: Patients are assigned to 1 of 2 treatment groups.

GROUP IIA: Lumpectomy patients undergo regional nodal radiation therapy with whole breast radiation therapy using IMRT or 3D-CRT QD 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity QD 5 days a week for 1-1/2 weeks.

GROUP IIB: Mastectomy patients undergo regional nodal radiation therapy using IMRT or 3D-CRT QD 5 days a week for 5 weeks.

All patients also receive systemic therapy as planned (hormonal therapy for patients with hormone-receptor positive breast cancer and trastuzumab or other anti-human epidermal growth factor receptor 2 [HER2] therapy for patients with breast cancer that is HER2-positive).

After completion of study treatment, patients are followed up at 6, 12, 18, and 24 months and then yearly for 8 years.

Are you eligible?

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

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; 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 provided that at least 2 sentinel lymph nodes are removed; removal of at least 3 sentinel lymph nodes and use of dual tracer for lymphatic mapping are strongly recommended 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 National Cancer Institute (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

Patient who have undergone either a total mastectomy or a lumpectomy are eligible; (patients who have had a nipple-sparing mastectomy 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