Image-Guided Intensity-Modulated Proton or Photon Beam Radiation Therapy with Boost in Treating Patients with Primary or Locally Recurrent Soft Tissue Sarcoma

Status: Active

Description

This phase I / II trial studies the side effects and the best dose of image-guided intensity-modulated proton or photon beam radiation therapy with boost and to see how well they work in treating patients with a single tumor (primary cancer) or cancer that has come back at or near the original tumor after a period of disappearing (locally recurrent). Specialized radiation therapy that delivers a high dose of radiation therapy directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

Eligibility Criteria

Inclusion Criteria

  • Participants must have histologically proven primary (or locally recurrent after prior surgery) soft tissue sarcoma of the retroperitoneum; patients in the phase II portion of the trial will be primary soft tissue sarcomas only; extraskeletal chondrosarcoma is allowed; pathology must be reviewed prior to study entry; NOTE: for patients with retroperitoneal neoplasms that have ambiguous histological and/or immunohistochemical findings, the diagnoses of carcinoma, melanoma, and lymphoma should be excluded by immunohistochemical studies with antibodies to broad spectrum cytokeratin (AE1/AE3), S-100, cluster of differentiation (CD)45, or LCA (leucocyte common antigen), respectively; if these diagnoses are excluded by immunohistochemistry, then patients presenting with primary non-visceral retroperitoneal masses that are felt to be "consistent with sarcoma" shall be considered eligible for this trial
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • No prior radiation therapy for retroperitoneal sarcoma is allowed
  • Life expectancy of greater than 2 years
  • Eastern Cooperative Group (ECOG) performance status =< 1
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] > 8.0 g/dl is acceptable)
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • For women of childbearing potential, negative urine or serum pregnancy test within 6 weeks prior to study entry
  • No distant metastases, based upon the following minimum diagnostic workup: * History and physical exam including a detailed description of the location, size and stage of the sarcoma, within 10 weeks prior to study entry * CT or magnetic resonance imaging (MRI) with contrast of the abdomen and pelvis within 8 weeks prior to study entry; the maximal dimension of the primary tumor will be measured in CT and MRI images; and * CT scan of the chest within 8 weeks prior to study entry
  • The effects of radiation therapy on the developing human fetus have been known to be teratogenic; women of child-bearing potential and men must agree to use adequate contraception (i.e. hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • The ability to understand and the willingness to sign a written informed consent document
  • Participant must be evaluated by surgical oncologist and felt to have potentially resectable tumor and be medically fit for proposed surgery

Exclusion Criteria

  • Participants who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry or those with adverse events due to agents administered more than 4 weeks earlier that have not resolved to =< grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4
  • Participants may not be receiving any other investigational agents
  • Participants with sarcoma of head and neck, lung, heart or extremity origin; or histopathology demonstrating rhabdomyosarcoma, extraosseous primitive neuroectodermal tumor (PNET) soft tissue Ewing's sarcoma, osteosarcoma, Kaposi's sarcoma, angiosarcoma, aggressive fibromatosis (desmoid tumor), or dermatofibrosarcoma protuberans or chondrosarcoma other than extraskeletal chondrosarcoma; or well differentiated liposarcoma where the target volume cannot be adequately distinguished from the normal retroperitoneal fat are excluded
  • Participants with multifocal disease, lymph node or distant metastases; Note: multiple pulmonary nodules < 8 mm without a histological diagnosis detected incidentally in a non-screening CT scan may not be a basis for study exclusion because of the sensitivity/specificity of the CT scans of the chest/abdomen/pelvis
  • History of sensitivity to, or history of conditions that are known to cause sensitivity to, radiation therapy
  • Participants for whom intraoperative or post-operative radiation therapy is planned as part of the overall primary tumor treatment
  • Uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because radiation is known to have teratogenic effects
  • Individuals with a history of a different invasive malignancy are eligible per the discretion of the treating investigator and review by the principal investigator
  • Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy are ineligible because of the potential for increased sensitivity to radiation therapy

Locations & Contacts

Illinois

Chicago
Rush University Medical Center
Status: Active
Contact: Dian Wang
Phone: 312-942-5498
Email: clinical_trials@rush.edu

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Contact: Elizabeth Healey Baldini
Phone: 617-732-6310
Email: ebaldini@partners.org
Dana-Farber Cancer Institute
Status: Active
Contact: Elizabeth Healey Baldini
Phone: 617-732-6310
Email: ebaldini@partners.org
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Thomas Francis Delaney
Phone: 617-726-6876
Email: tdelaney@partners.org

Minnesota

Rochester
Mayo Clinic
Status: Active
Contact: Ivy A. Petersen
Phone: 507-284-2669
Email: Peterson.ivy@mayo.edu

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Contact: John Michael Kane
Phone: 716-845-3284
Email: john.kane@roswellpark.org

North Carolina

Durham
Duke University Medical Center
Status: Active
Contact: Dan German Blazer
Phone: 919-684-6553
Email: Trey.blazer@duke.edu

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Andrew J. Bishop
Phone: 713-563-2300
Email: ABishop2@mdanderson.org

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Ying Jia Hitchcock
Phone: 801-581-4477
Email: clinical.trials@hci.utah.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of preoperative image-guided (IG)-intensity-modulated proton radiation therapy (IMPT) and intensity-modulated photon radiation therapy (IMRT) with simultaneously integrated boost to the high risk margin of retroperitoneal sarcoma. (Phase I)

II. To determine the local control rate after the protocol treatment (IG-IMPT or IMRT MTD with simultaneously integrated boost to the high risk margin) followed by surgical resection. (Phase II)

SECONDARY OBJECTIVES:

I. To estimate overall survival.

II. To estimate pathologic response (percentage of necrosis and margin status, especially status of the high-risk margin).

III. To estimate the tumor response through the comparison of computed tomography (CT) imaging before and after the protocol treatment.

IV. To explore progression-free survival times relative to surrogate biological endpoints in tissue and blood in participants enrolled at Massachusetts General Hospital (MGH).

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients undergo IG-IMPT or IG-IMRT with simultaneously integrated boost (SIB) to the high-risk margin 5 days a week for approximately 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 and 4 months, twice yearly for 5 years and then once yearly for 5 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Thomas Francis Delaney

Trial IDs

Primary ID 12-100
Secondary IDs NCI-2012-01931
Clinicaltrials.gov ID NCT01659203