Neoplasms

All Conditions

Symptoms and General Pathology

Rare Diseases

Sarcoma

Liposarcoma

Recurrence

Leiomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Preoperative external beam radiotherapy (RT) combined with doxorubicin (DOX) and followed by intraoperative radiotherapy (IORT); dose-escalation study of external beam radiotherapy.

Doxorubicin IV bolus followed immediately by IV over 4 days every week for 5 weeks concurrently with external beam radiotherapy 5 days a week for 4 weeks.

Doxorubicin hydrochloride (DOX)

Surgical resection of primary tumor and all adjacent gross disease approximately 6 weeks after chemoradiotherapy

Conventional surgery

Intraoperative radiotherapy (IORT) to tumor bed if all gross disease has been resected and if area of maximal tumor adherence to retroperitoneum can be encompassed within a single IORT field (maximum 15 cm).

Intraoperative radiation therapy (IORT)

Radiation Therapy (RT)

Peter W. Pisters, MD

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of radiation therapy plus doxorubicin in treating patients who have resectable primary or recurrent peritoneal soft tissue sarcoma.

OBJECTIVES: I. Determine the toxicity and maximum tolerated dose of preoperative external beam radiotherapy when combined with doxorubicin and followed by intraoperative radiotherapy in patients with resectable primary or recurrent soft tissue sarcoma of the retroperitoneum. II. Assess radiologic and pathologic response in patients treated with this preoperative regimen.

OUTLINE: This is a dose-escalation study of external beam radiotherapy. Patients receive doxorubicin IV bolus followed immediately by doxorubicin IV over 4 days every week for 5 weeks concurrently with external beam radiotherapy 5 days a week for 4 weeks. Patients with stable or responding disease undergo surgical resection of primary tumor and all adjacent gross disease approximately 6 weeks after completion of chemoradiotherapy. Patients receive intraoperative radiotherapy (IORT) to the tumor bed if all gross disease has been resected and if the area of maximal tumor adherence to the retroperitoneum can be encompassed within a single IORT field (maximum 15 cm). Cohorts of 3-6 patients receive escalating doses of external beam radiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 30% of patients experience grade 3 or worse dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 15-45 patients will be accrued for this study.

Radiation Therapy Plus Doxorubicin in Treating Patients With Resectable Primary or Recurrent Retroperitoneal Soft Tissue Sarcoma

A Phase I Study of Preoperative Chemoradiation and Intraoperative Radiation Therapy in the Treatment of Retroperitoneal Sarcoma

The MTD is defined as the dose at which 30% of patients experience grade 3 or worse dose-limiting toxicity

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants receive 'Merck 3475 Pembrolizumab' by vein one to two times before Intraoperative radiation therapy (IORT).

The Intrabeam® Photon Radiosurgery System is a miniature electron beam-driven X-ray source which provides a point source of low energy X-rays (50 kV maximum) at the tip of a 3.2 mm diameter tube. The radiation source can be inserted into the area of interest immediately after excision of the tumor and switched on for 20-35 minutes to provide intraoperative radiotherapy accurately targeted to the tissues that are at the highest risk of local recurrence. The dosimetric characteristics and early clinical applications of this device have been well studied and this is the device which was utilized in the international TARGIT trial.

Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of one to two cycles.

Merck 3475 Pembrolizumab

Participants will receive Intraoperative radiation therapy (IORT) on the day of surgery.

Eileen Connolly, MD

Radiation Oncology Research Department

Jane Meisel, MD

William Small, MD

Mariamne Reyna

Eileen Connolly, MD, PhD

Assess response to pembrolizumab in both primary tumor, normal breast stroma, circulating lymphocytes and serum exosomes in treatment naive triple negative breast cancer (TNBC) patients.

Assess for change in tumor-infiltrating lymphocytes (TILS) both stromal (sTILS) and intraepithelial (iTILS) in newly diagnosed early stage TNBC patients treated with two doses of MK-3475 prior to lumpectomy.

This is an open-label, single-arm, single institution pre-operative "window of opportunity study" of pembrolizumab in subjects with newly diagnosed triple-negative, \< 3 cm, node negative breast cancer. Subjects may not have received any prior neo/adjuvant chemotherapy, definitive surgery or radiation treatment prior to enrollment.

The goal of this project is to determine if immune modulation through treatment with MK-3475 (Pembrolizumab) in triple negative breast cancer (TNBC) patients will alter expression of immune tolerant markers \[including PD-L1\], within the primary tumor. Investigators hope to determine if MK-3475 exposure will change the molecular signature of breast stroma from "normal" adjacent breast tissue (non-tumor tissue) obtained prospectively at the time of breast conserving surgery (BCS) in TNBC patients. Finally, investigators will investigate how pembrolizumab alters breast stromal response to high dose radiation delivered by intraoperative radiation therapy (IORT).

Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer

Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer With and Without Intra-operative RT: a Window of Opportunity Study

This outcome measure is designed to determine if immune modulation therapy with MK-3475 will increase TILs in newly diagnosed TNBC tumors. The mean percent change in TILS in tumor tissue from initial core biopsy samples will be compared with pathology samples from definitive surgery after two cycles of MK-3475.

Merck Sharp & Dohme LLC

Eileen Connolly

Assistant Professor of Radiation Oncology

Carcinoma

Carcinoma in Situ

Breast Carcinoma In Situ

Neoplasms, Glandular and Epithelial

All participants who plan to undergo partial mastectomy for treatment of early stage breast cancer will be considered for eligibility for IORT. Patient with single breast cancer less than 3cm in disease span, clinical negative axillary node will be offered the option of having IORT. If IORT is delivered following surgical resection of the tumor they will be followed in this registry for short and long term outcomes.

IORT involving 50kV Xrays to a dose of 20 Gy during breast-conserving surgery

Intraoperative Radiation Therapy (IORT)

Janie Grumley, MD

Robert Wollman, MD

Lisa Chaiken, MD

This is a prospective, registry study that will enroll all women with early stage breast cancer who will be treated with intraoperative radiotherapy (IORT) during breast-conserving surgery. The purpose of this study is to further validate the long-term effectiveness and safety of this treatment method. We aim to assess short and long-term patient outcomes associated with IORT, including perioperative complications, local and distance disease recurrences, as well as disease-free survival and overall survival.

At Providence Saint John's Health Center, there is the ongoing integration of Intra-Operative Radiation Therapy (IORT) as a standard treatment option among Breast Conserving Therapy (BCT) for individuals with in situ and early stage breast cancer. Currently, approximately 60 women per year are being treated with IORT. No repository of information of patient outcomes with this treatment has been established. This leaves a critical gap in the ability to assess the long-term outcomes of patients treated with IORT.

As the practice of using IORT to treat early stage and in situ breast cancer continues to grow at Providence Saint John's Health Center, this registry will provide the data needed to compare patient outcomes with those being treated with the traditional whole breast radiation therapy. In addition, the Providence Health \& Services strives to improve patient care and outcomes with excellence whenever possible. The registry will provide the data needed to compare patient outcomes to national and community standards that can inform internal practice patterns and contribute to advancing breast cancer care nationally and internationally.

Registry for Intra-Operative Radiotherapy During Breast Conserving Surgery in Patients With Early Stage Breast Cancer

Research Registry for Intra-Operative Radiotherapy (IORT) During Breast Conserving Surgery in Patients With in Situ and Early Stage Breast Cancer

Presence of recurrent tumor in ipsilateral breast or distant site

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiation Therapy Plus Doxorubicin in Treating Patients With Resectable Primary or Recurrent Retroperitoneal Soft Tissue Sarcoma	NCT00004123	Sarcoma	Doxorubicin hyd... Conventional su... Intraoperative ... Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer	NCT02977468	Triple Negative...	Merck 3475 Pemb... Intraoperative ...	21 Years - 80 Years	Columbia University
Registry for Intra-Operative Radiotherapy During Breast Conserving Surgery in Patients With Early Stage Breast Cancer	NCT04603209	Early-stage Bre... Breast Carcinom... Breast Neoplasm...	Intraoperative ...	18 Years -	Saint John's Cancer Institute

Spots Global Cancer Trial Database for intraoperative radiation therapy (iort)