Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Adenocarcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Carboplatin

Doxorubicin

Liposomal doxorubicin

Docetaxel

270 cGy (centigray) x 15 concurrent with chemotherapy of the treating medical oncologist's choice

PBI with sequential chemotherapy

270 cGy x15 concurrent with chemotherapy of the treating medical oncologist's choice

PBI with concurrent chemotherapy

Richard Zellars, MD

In a small study at Johns Hopkins, women were treated with partial breast irradiation and chemotherapy given at the same time.

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.

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 or positive 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

Randomized trial of Partial Breast Irradiation (PBI) with concurrent or sequential chemotherapy

Partial Irradiation and Sequential vs. Concurrent Chemo Early Breast Cancer

Randomized Phase II Study of Partial Breast Irradiation and Sequential vs. Concurrent Chemotherapy in Women With Early Stage Breast Cancer (PBI 3.0)

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.

Evaluate and compare any first tumor recurrence (local plus distant) between arms of the study.

Evaluate long term skin toxicity with concurrent chemotherapy and compare between arms of the study.

Evaluate and compare Ipsilateral Breast Tumor Recurrence (IBTR), local recurrence, distant recurrence, and disease free survival.

Give a description of the risks and benefits observed in each arm of the study over the duration of the trial.

Richard Zellars

Professor and Chairman of the Department of Radiation Oncology

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

AC \[Adriamycin (A) (also known as doxorubicin) and Cyclophosphamide (C)\] Followed By Paclitaxel (P)

AC [Adriamycin (A) (also known as doxorubicin) and Cyclophosphamide (C)] Followed By Paclitaxel (P)

Chau Dang, MD

HER-2/neu (+) breast cancer is a more aggressive form of breast cancer. HER-2/neu is a protein that is overproduced by your tumor. It makes your cancer more aggressive. Standard treatments for this type of cancer will help some people, but there is a moderate to high chance that your cancer may come back.

The purpose of this study is to see if a new regimen will be effective in preventing cancer from coming back. This is a phase II trial. In this trial, patient get a drug regimen that has been tested in small groups of people to see what dose is safe. Researchers now wish to see how effective the drug is for HER-2/neu (+) breast cancer. The objective includes looking at short-term side effects and risks of the drug. All of the drugs on this regimen can affect the heart which can be a serious side effect. The drugs affect on heart function is a primary focus.

Phase II Study of Dose-Dense Doxurubicin and Cyclophosphamide (AC) Followed By Paclitaxel With Trastuzumab in HER2/ NEU-Amplified Breast Cancer: Feasibility

Amgen

Genentech, Inc.

Memorial Sloan Kettering Cancer Center

Doxorubicin and Cyclophosphamide (60/600 mg/m2) X 4 followed by Paclitaxel (175 mg/m2) X 4 every 2 weekly with pegfilgrastim (6mg on day 2) + Trastuzumab x 1 year.

AC Followed by Paclitaxel + Trastuzumab

Age, Continuous

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Dr. Chau Dang

LVEF at Baseline

LVEF at Month 2

LVEF at Month 6 (67/70 pts)

LVEF at Month 9 (68/70 pts)

LVEF at Month 18 (48/70 pts)

Cardiac Saftey

Overall Study

Epirubicin

The regimen consists of EC (epirubicin 100 mg/m2, cyclophosphamide 600 mg/m2) q 14 days x 6 with pegfilgrastim subcutaneously (SQ) on day # 2, followed by paclitaxel (175 mg/m2) q 14 days x 6 with pegfilgrastim SQ on day # 2.

EC (epirubicin 100 mg/m2, cyclophosphamide 600 mg/m2) q 14 days x 6 treatments with pegfilgrastim SQ day # 2 (6 mg). Paclitaxel (175 mg/m2) q 14 days x 6 treatments with pegfilgrastim SQ day # 2 (6 mg).

epirubicin, cyclophosphamide, Paclitaxel,

The purpose of this study is to give a drug regimen that is hoped to be effective in preventing cancer from coming back. Since it is an aggressive breast cancer, there is a moderate to high chance that the cancer may come back. The standard treatment for this tumor type includes a chemotherapy regimen with drugs named epirubicin (E) and cyclophosphamide (C) in a vein every 2 weeks for 4 treatments, followed by a drug named paclitaxel, every 2 weeks in your vein for 4 treatments.

This study is an experimental study in which you will be given 6 cycles of EC followed by 6 cycles of paclitaxel. The purpose of getting 2 more cycles of EC and 2 more cycles of paclitaxel than what is normally given is to study a regimen that may be more effective than the current standard treatment in preventing the recurrence of this cancer. Specifically, in this study we are looking for side-effects and risks of these drugs as more cycles are given.

Dose-Dense Epirubicin and Cyclophosphamide (EC) Followed by Paclitaxel in Breast Cancer: Feasibility

Pilot Study of Dose-Dense Epirubicin and Cyclophosphamide (EC) Followed by Paclitaxel in High-Risk Breast Cancer: Feasibility

Pfizer

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Monet Bowling, MD

The objective of this study is to identify and validate metastasis protein markers in lymph collected from women with metastatic breast cancer. We will examine peripheral blood for the presence of these identified markers in order to develop a user friendly clinical test to detect metastasis and to evaluate response to therapy.

The goal of the study is to identify node-negative breast cancer patients who are unlikely to benefit from adjuvant chemotherapy, thus saving them from the adverse effects of unnecessary treatment. We propose to identify and validate protein markers that can determine breast cancer recurrence and metastasis, based on an approach our group has recently found highly promising for biomarker discovery.

The objective of our research is to identify and validate metastasis protein markers in lymph collected from vessels exiting from the primary tumor and prior to their entry into sentinel lymph node in women with metastatic breast cancer. Realizing that this novel procedure cannot be adopted for routine clinical use, we will examine the peripheral blood for the presence of these identified markers in order to develop a user friendly clinical test to detect metastasis and to evaluate response to therapy.

Lymph Fluid and Blood Collection for Identification of Novel Biomarkers

The Comparison of Lymph Fluid and Blood From Metastatic and Non-metastatic Invasive Breast Cancer Patients for Identification of Novel Biomarkers

Lymph fluid collected at surgery; blood collected at surgery and then every 6 months for 5 years.

Indiana University

Immune System Diseases

Hypersensitivity

pre-operative radiation of the in situ tumor in the breast

before treatment a biopsy will be taken to confirm breast cancer type

biopsy

at FNA tumor material will be collected and fresh frozen for micro-analyses; parafin embedded tissue will bestored for tissue-array analysis

fine-needle aspiration

accelerated partial breast irradiation

image-guided radiation therapy

Paula Elkhuizen, MD

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving CT-guided accelerated radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This clinical trial is studying giving radiation therapy followed by surgery to see how well it works in treating patients with early-stage breast cancer.

OBJECTIVES:

* is to investigate the impact of a short fractionated schedule given preoperatively on local control, cosmesis and breast fibrosis.
* To further design optimal treatment strategies for individual breast cancer patients treated with breast-conserving therapy (BCT) on the basis of biological parameters, including the expression profile of the primary tumor, for both m-RNA as for micro-RNA, with first, a focus on radiotherapy responsiveness and second, on local recurrence rate, distant metastases and survival.
* proteomics will be studied in fine-needle aspiration samples. A classifier can be build (genomic or proteomic or any kind of molecular signature) to identify responders and non-responders
* quality of life

OUTLINE: Patients undergo image-guided preoperative accelerated partial-breast irradiation (PAPBI) 10 times over 12 days (10 x 4 Gy) and later in the study 5 times 6 Gy. Six weeks after completion of image-guided PAPBI, patients undergo surgery.

Radiation Therapy Followed by Surgery in Treating Patients With Early-Stage Breast Cancer

Image Guided Preoperative Accelerated Partial Breast Irradiation (PAPBI): Defining Radiotherapy Sensitivity

Local recurrences should not exceed 4% at 5 years of follow-up

decrease from 27% as found in the boost arm of the EORTC boost-no boost trial to 15%

is anticipated that the overall score for cosmetic outcome will be superior compared to conventional whole breast postoperative radiotherapy plus boost.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Partial Irradiation and Sequential vs. Concurrent Chemo Early Breast Cancer	NCT01928589	Breast Cancer Adenocarcinoma ...	PBI with sequen... PBI with concur...	18 Years - 100 Years	Indiana University
Phase II Study of Dose-Dense Doxurubicin and Cyclophosphamide (AC) Followed By Paclitaxel With Trastuzumab in HER2/ NEU-Amplified Breast Cancer: Feasibility	NCT00591851	Breast Cancer	AC [Adriamycin ...	18 Years -	Memorial Sloan Kettering Cancer Center
Partial Irradiation and Sequential vs. Concurrent Chemo Early Breast Cancer	NCT01928589	Breast Cancer Adenocarcinoma ...	PBI with sequen... PBI with concur...	18 Years - 100 Years	Indiana University
Dose-Dense Epirubicin and Cyclophosphamide (EC) Followed by Paclitaxel in Breast Cancer: Feasibility	NCT00617370	Breast Cancer Adenocarcinoma ...	epirubicin, cyc...	18 Years -	Memorial Sloan Kettering Cancer Center
Lymph Fluid and Blood Collection for Identification of Novel Biomarkers	NCT01075607	Adenocarcinoma ...		18 Years - 80 Years	Indiana University
Radiation Therapy Followed by Surgery in Treating Patients With Early-Stage Breast Cancer	NCT01024582	Breast Cancer	biopsy fine-needle asp... accelerated par... image-guided ra...	60 Years - 120 Years	The Netherlands Cancer Institute
Dose-Dense Epirubicin and Cyclophosphamide (EC) Followed by Paclitaxel in Breast Cancer: Feasibility	NCT00617370	Breast Cancer Adenocarcinoma ...	epirubicin, cyc...	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for adenocarcinoma of the breast