Partial Breast Irradiation With Concurrent Chemotherapy for Women With Breast Cancer (PBI 3)
Women with ER negative breast cancer have a higher risk of the cancer returning in the breast after whole or partial breast radiation than women with ER positive breast cancer. In a small study at Johns Hopkins, women were treated with partial breast irradiation and chemotherapy given at the same time. This combined treatment was safe and women with ER negative breast cancer did just as well as women with ER positive cancer.
We are now testing in a bigger study whether giving partial breast irradiation and chemotherapy at the same time (our new method) has the same side effects and outcomes as giving partial breast irradiation and chemotherapy at different times(older method). In this study women who had their breast cancer removed but need radiation to the breast will be randomized to partial breast irradiation at the same time as chemotherapy or partial breast radiation at a different time than chemotherapy. Randomization is like flipping a coin but in this study about 2 of every 3 women will get the new method.
Adenocarcinoma of the Breast
Other: PBI with chemotherapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||"Randomized Trial of Partial Breast Irradiation (PBI) and Sequential vs. Concurrent Chemotherapy in Women With ER Negative Early Stage Breast Cancer (PBI 3.0)"|
- Grade 3 or 4 short-term toxicity [ Time Frame: 6-7 month follow-up ] [ Designated as safety issue: Yes ]The primary endpoint will be short term (from baseline to the 6-7 month follow-up) grade 3 or 4 toxicity: confluent moist desquamation, pitting edema, ulceration, hemorrhage or necrosis. Our primary objective is to determine if chemotherapy and PBI can be given concurrently with short term toxicity comparable to standard of care, whole breast radiation (WBR) without chemotherapy, and not inferior to that of PBI plus chemotherapy given sequentially.
- 1st tumor recurrence [ Time Frame: 6-7 months ] [ Designated as safety issue: No ]Evaluate and compare any first tumor recurrence (local plus distant) between arms of the study.
- Long-term grade 3-4 toxicities [ Time Frame: Q6-12M 12-18, 24-30, 36-42, 48-54, 60-66, 72-78, 84-90, 96-108, 120 ] [ Designated as safety issue: Yes ]Evaluate long term toxicity with concurrent chemotherapy and compare between arms of the study.
- Time to tumor recurrence [ Time Frame: Q6-12M 12-18, 24-30, 36-42, 48-54, 60-66, 72-78, 84-90, 96-108, 120 ] [ Designated as safety issue: No ]Evaluate and compare Ipsilateral Breast Tumor Recurrence (IBTR), local recurrence, distant recurrence, and disease free survival.
- Quality of Life assessment [ Time Frame: Q6-12M 12-18, 24-30, 36-42, 48-54, 60-66, 72-78, 84-90, 96-108, 120 ] [ Designated as safety issue: No ]Evaluate and compare quality of life.
- Quantify risks and benefits comparison for each arm [ Time Frame: Q6-12M 12-18, 24-30, 36-42, 48-54, 60-66, 72-78, 84-90, 96-108, 120 ] [ Designated as safety issue: Yes ]Give a description of the risks and benefits observed in each arm of the study over the duration of the trial.
|Study Start Date:||September 2013|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Active Comparator: PBI
270 cGy (centigray) x 15
270 cGy x15
Other Name: partial breast irradiation
Experimental: PBI with chemotherapy
270 cGy (centigray) x 15 concurrent with chemotherapy of the treating medical oncologist's choice
Other: PBI with chemotherapy
270 cGy x15 concurrent with chemotherapy of the treating medical oncologist's choice
Other Name: partial breast irradiation with chemotherapy
Hide Detailed Description
Breast conserving therapy (BCT) defined as lumpectomy and adjuvant whole breast irradiation (WBI) is integral to the treatment of early stage breast cancer (ESBC). In these patients, BCT provides equivalent survival to mastectomy. Despite equivalent survival, many patients still choose mastectomy over the BCT in light of the 5-7 week commitment required for radiation therapy (XRT). Partial breast irradiation, however, has provided women with ESBC an alternative option for XRT. Worth noting, is PBI offers several advantages over WBI including; decreased duration of XRT, and reduced radiation dose delivery to normal breast tissue and surrounding organs.
Several large trials have advanced the adoption of PBI as a treatment option for women with ESBC. Results of these trials unfortunately differ in regards to patient outcomes. Some trials report no significant difference in the local failure rate (LFR) between intraoperative radiation therapy, interstitial brachytherapy and standard WBI following lumpectomy (Vaidya et al. Lancet 2010; Polgar et al. IJROBP 2004). While others, have demonstrated similar outcomes for PBI and WBI only apply to a select group of patients. (Khan et al. International Journal of Radiation Oncology *Biology *Physics (IJROBP) 2012; Shaitelman et al. Cancer 2010; Stull et al. ASTRO 2012).
A growing body of evidence now suggests, that there is in fact a subgroup of patients for which PBI may not be appropriate. In particular, patients with estrogen receptor (ER) negative tumors have been observed to have higher LFR than patients with ER positive tumors. Stull et al. reported a 3-year LFR of 2% and 12% in ER positive (n=149) and ER negative (n=17) tumors, respectively (Stull et al. ASO 2012). Additionally, Shaitelman et al. reviewed patients treated on the Mammosite registry and found the hazard ratio for local failure was 4.01 in women with ER negative compared to ER positive disease (n=991). (Shaitelman et al. Cancer 2010)
To address the variation in patient outcomes for women treated with PBI, American Society for Radiation Oncology (ASTRO) published a consensus statement grouping patients into "suitable," "cautionary," or "unsuitable" categories. These groupings sought to identify populations best suited for PBI. Patients with ER negative breast cancer were assigned to either the cautionary or unsuitable categories. Shah et al. published a pooled analysis (n=1978) that found the only significant factor associated with ipsilateral breast recurrence (IBRT ) in women who received PBI was ER status. (Shah et al. IJROBP 2012). Leonardi et al. reported similar findings; local recurrence was 2.68 (p = 0.0003) more likely in ER negative (n=189) than in ER positive (n=1608) breast cancers (Leonardi et al. IJROBP 2012). These results suggest that perhaps, patients with ER negative disease are not the most appropriate patients to be treated with PBI.
In addition to radiation therapy, patients are often treated with chemotherapy. Chemotherapy has traditionally been administered either before or after PBI. There are potentially significant benefits, however, that can be gained by the simultaneous administration of chemotherapy and PBI. Administrations of radiation with concurrent chemotherapy soon after surgery will not only shorten the overall duration of therapy, but has the potential to capitalize on the synergy between the two treatment modalities and improve local control. Reports of prohibitive toxicity with concurrent administration of anthracycline-based chemotherapy with WBI have made this approach unpopular. The smaller fields employed during PBI may provide an alternative option. PBI has the potential to reduce toxicity and accelerate the radiation treatment schedule.
To date, we have been able to conduct two phase I trials of PBI and concurrent chemotherapy (PBICC). In both trials we tested whether the toxicity remained prohibitive with this combined treatment regimen. In the first trial, 25 patients were treated with PBI and concurrent dose dense doxorubicin and cyclophosphamide. In the second trial, 34 patients were treated similarly but selection of the chemotherapy regimen was at the discretion of the treating medical oncologist. Results from both trials revealed that PBICC well appears to be tolerated. Specifically, there was no grade 3 or 4 acute or late radiation induced toxicity in either trial. Although these trials were not powered for local failure, one significant finding from these trials was there were no local failures in the first trial (median follow up 6 years), and only one failure (low grade DCIS) in the second trial (median follow up 2.5 years). Interestingly, there were no recurrences in the 21 patients with ER negative tumors or the 17 patients with triple negative tumors.
Our center is the only center to have investigated and published phase I trials of PBICC. Through these trials we have demonstrated preliminary information that PBICC is safe, feasible, and effective treatment option for women with ESBC. Based on our unique experience, we hypothesize that women with ER negative ESBC treated with PBICC will have local control rates similar to women with ER positive disease. Additionally, we hypothesize that women placed in the prone position will have an even more favorable toxicity profile than women placed in the supine position for both PBI and WBI. To further substantiate the low toxicity associated with PBICC and to test this our improved local control hypothesis, we will conduct a randomized prospective trial of PBI with concurrent vs. sequential chemotherapy in women with ER negative ESBC. Our primary endpoint is acute grade 3-4 radiation toxicity and our secondary endpoints will be local control and breast specific quality of life
Please refer to this study by its ClinicalTrials.gov identifier: NCT01928589
|Contact: Richard Zellars, MDfirstname.lastname@example.org|
|Contact: Shirley DiPasquale, RNemail@example.com|
|United States, Maryland|
|Anne Arundel Medical Center||Not yet recruiting|
|Annapolis, Maryland, United States, 21401|
|Contact: Elizabeth Egan, RN 443-481-5811 firstname.lastname@example.org|
|Principal Investigator: Mary Young, MD|
|The SKCCC at Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Richard Zellars, MD 410-502-1421 email@example.com|
|Contact: Shirley DiPasquale, RN 410-614-1598 firstname.lastname@example.org|
|Sub-Investigator: Nita Ahuja, MD|
|Sub-Investigator: Deborah Armstrong, MD|
|Sub-Investigator: Fariba Asrari, MD|
|Sub-Investigator: Melissa Camp, MD|
|Sub-Investigator: Lana De Souza Lawrence, MD|
|Sub-Investigator: Leisha Emens, MD|
|Sub-Investigator: John Fetting, MD|
|Sub-Investigator: Deborah Frassica, MD|
|Sub-Investigator: Mehran Habibi, MD|
|Sub-Investigator: Julie Lange, MD|
|Sub-Investigator: Todd McNutt, PhD|
|Sub-Investigator: Lee Myers, PhD|
|Sub-Investigator: Antonio Wolff, MD|
|Sub-Investigator: Harvey Ziessman, MD|
|Suburban Hospital||Not yet recruiting|
|Bethesda, Maryland, United States, 20814|
|Contact: Julie Ambrozak, RN 301-896-2016 email@example.com|
|Principal Investigator: Susan Stinson, MD|
|Sibley Memorial Hospital||Not yet recruiting|
|District of Columbia, Maryland, United States, 20016|
|Contact: Amanda Moser 202-660-6420 firstname.lastname@example.org|
|Principal Investigator: Victoria Croog, MD|
|United States, Pennsylvania|
|Reading Hospital||Not yet recruiting|
|West Reading, Pennsylvania, United States, 19611|
|Contact: Pat Weiser, RN 484-628-8193 email@example.com|
|Principal Investigator: Michael Haas, MD|
|York Cancer Center||Not yet recruiting|
|York, Pennsylvania, United States, 17403|
|Contact: Debi Oxenberg, RN 717-741-8124 firstname.lastname@example.org|
|Principal Investigator: Amit Shah, MD|
|Principal Investigator:||Richard Zellars, MD||The SKCCC at Johns Hopkins|