Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Wounds and Injuries

Rare Diseases

Fibrosis

Sarcoma

Lymphedema

Chondrosarcoma

Radiation Fibrosis Syndrome

Syndrome

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Lymphatic Diseases

Radiation Injuries

Soft Tissue Sarcoma

Radiation therapy with neoadjuvant or adjuvant or concurrent or interdigitated chemotherapy followed by surgery followed by, for patients with positive margins, radiation therapy boost

Radiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost

Up to 6 courses of investigator's choice of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy

Chemotherapy

Preoperative IGRT (3D-CRT or IMRT): If receiving neoadjuvant or adjuvant chemotherapy or no chemotherapy: 50 Gy (2 Gy once a day, 5 times a week). If receiving concurrent or interdigitated chemotherapy: 44 Gy (2 Gy once a day, 5 times a week). Postoperative radiotherapy boost for patients with positive margins following surgery: 16 Gy (2 Gy once a day, 5 times a week) external beam radiation therapy or 16 Gy at ≤ 80 cGy per hour brachytherapy or 3.4 Gy/fraction in 4 fractions brachytherapy or 10-12.5 Gy in a single fraction intraoperative radiation therapy boost.

Radiation therapy

Resection of the sarcoma with the goal of having negative pathologic margins. Every effort should be made to have limb preservation surgery unless there is documented evidence of tumor progression that would require amputation for an appropriate negative margin resection. All lesions of the extremities should be treated with wide excision.

Surgery

Dian Wang, MD, PhD

Scott Okuno, MD

Burton L. Eisenberg, MD

John M. Kane, MD

David G. Kirsch, MD, PhD

RATIONALE: Image-guided radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a lower dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PURPOSE: This phase II trial is studying the side effects and how well image-guided radiation therapy works in treating patients with primary soft tissue sarcoma of the shoulder, arm, hip, or leg.

OBJECTIVES:

Primary

* To determine the effect of reduced radiation volume using image-guided radiotherapy (IGRT) on lymphedema ≥ grade 2, subcutaneous fibrosis, and joint stiffness at 2 years in patients with primary soft tissue sarcoma of the extremity.

Secondary

* To estimate the rates of other grade 3-5 adverse events as measured by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0.
* To determine the pattern of first failure, including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression.
* To estimate the rates of local failure, local-regional failure, distant failure, distant disease-free survival, disease-free survival, overall survival, and second primary tumor.
* To estimate the rate of wound complications.
* To correlate the degree of late radiation morbidity (defined as any lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years with scores on the clinical measure, Musculoskeletal Tumor Rating Scale (MSTS).

OUTLINE: This is a multicenter study.

* Neoadjuvant radiotherapy: Patients are assigned to 1 of 2 treatment groups (group 1 closed to accrual as of 01/08/10).

  * Group 1 (closed to accrual as of 01/08/10): Patients undergo 3-D conformal radiotherapy (3D-CRT) or intensity-modulated therapy (IMRT) once daily, 5 days a week, for 4½-5 weeks. Patients also receive up to 6 courses of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy.
  * Group 2: Patients undergo 3D-CRT or IMRT once daily, 5 days a week, for 5 weeks.
* Surgery: At 4-8 weeks after completion of neoadjuvant radiotherapy, patients undergo surgical resection of the tumor. Patients with positive tumor margins (residual tumor) undergo intraoperative radiotherapy boost or proceed to adjuvant radiotherapy within 2 weeks after surgery.
* Adjuvant radiotherapy: Patients undergo either external-beam radiotherapy (EBRT) once daily for 8 fractions or brachytherapy.

After completion of study treatment, patients are followed at least every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Image-Guided Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Shoulder, Arm, Hip, or Leg

A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity

The rate of patients with late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years from the start of radiotherapy as measured by EORTC(European Organisation for Research and Treatment of Cancer)/RTOG (Radiation Therapy Oncology Group) criteria. Grade refers to the severity of the morbidity. The RTOG/EORTC Late Radiation Morbidity Scoring Schema assigns Grades 1 through 5 with unique clinical descriptions of severity for each morbidity based on this general guideline: Grade 1 Mild , Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to morbidity.

Local failure is defined as the time from registration to date of failure (local progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.

Regional failure is defined as the time from registration to date of failure (regional progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.

Distant failure is defined as the time from registration to date of failure (distant progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.

Distant disease-free survival is defined as the time from registration to date of failure (distant progression or death) or last follow-up. Two year rate and 95% confidence interval were estimated by the Kaplan-Meier method.

Disease-free survival is defined as the time from registration to date of failure (local, regional, or distant progression or death) or last follow-up. Two year rate and 95% confidence interval were estimated by the Kaplan-Meier method.

Overall survival is defined as the time from registration to date of death or last follow-up. Two year survival rate and 95% confidence interval were estimated by the Kaplan-Meier method.

Second primary tumor is defined as the time from registration to date of failure (second primary tumor) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.

Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

Estimate rate of patients with acute wound complications with 95% confidence interval assuming binomial distribution.

Pattern of first failure including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression.

The Musculoskeletal Tumor Rating Scale (MSTS) is a measure of physical function across 7 items, completed by the physician (preferably by the Orthopedic Surgeon or Surgical Oncologist) or the physician's designated staff. The 7 items are: pain, range of motion, strength, joint stability, joint deformity, emotional, acceptance, and overall function. Each item is scored from 0-5 (worst possible to best possible condition). The item scores are summed to get the total score which ranges from 0-35.

Late radiation morbidity is defined as ≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

National Cancer Institute (NCI)

NRG Oncology

Radiation Therapy Oncology Group

Subjects experiencing more than one of a given adverse event (AE) are counted only once for that adverse event. Data is reported for eligible patients with adverse event data who started study treatment.

Cohort A - Chemotherapy

Cohort B - No Chemotherapy

Total

Age, Continuous

Sex: Female, Male

All eligible patients who started protocol treatment.

Due to unmet accrual goals for Cohort A, the decision was made to close this cohort and to increase the sample size of Cohort B. Due to the small sample size for Cohort A results were not reported.

Wendy Seiferheld, M.S.

Initially designed to test for a 20% absolute improvement from 37% (fixed rate) to 17% using Fisher's exact test, requiring 41 patients per cohort (51 with 20% ineligibility) with 5% type I error and 90% statistical power. During accrual, the sample size for cohort B was increased to 66 (83 with 20% ineligibility) to test for a 15% improvement with 5% type I error and 85% power.

All eligible patients on Cohort B who started study treatment and had an assessment of toxicity at 2 years. (See limitations and caveats, Cohort A is not included.)

Rate of Late Radiation Morbidity (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis, or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by EORTC/RTOG Criteria

All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)

Local Failure Rate at Two Years

Regional Failure Rate at Two Years

Distant Failure Rate at Two Years

Distant Disease-free Survival Rate at Two Years

Disease-free Survival Rate at Two Years

Overall Survival Rate at Two Years

Second Primary Tumor Rate at Two Years

Late Radiation Morbidity Rate (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by CTCAE v3.0

All eligible patients on cohort B that had surgery and a wound assessment. (See limitations and caveats, Cohort A is not included.)

Percentage of Patients With Wound Complications

Local

Regional

Distant

Dead without disease progression

Alive without disease progression

All eligible patients on Cohort B who started study treatment. All eligible patients on Cohort B. (See limitations and caveats, Cohort A is not included.)

Pattern of First Failure

No Late Radiation Morbitity

Has Late Radiation Toxicity

All eligible patients on Cohort B who had a 2-year MSTS assessment. (See limitations and caveats, Cohort A is not included.)

Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years

Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events

Correlation of Late Radiation Morbidity at 2 Years With the 3 Quality of Life Assessments [Functional Assessment of Cancer Therapy-General (FACTG), Toronto Extremity Salvage Score (TESS), and Sexual Adjustment Questionnaire (SAQ)]

Comparison of TESS and the MSTS Scores at 2 Years Between Cohort B Patients and the Preoperative Radiotherapy Patients in the NCIC CTG Trial [National Cancer Institute of Canada Clinical Trials Group]

Comparison of SAQ Scores at 2 Years for Cohort A Patients With Cohort B Patients

Overall Study

Nervous System Diseases

Recurrence

Liposarcoma

Histiocytoma, Malignant Fibrous

Fibrosarcoma

Histiocytoma

Histiocytoma, Benign Fibrous

Hemangiosarcoma

Leiomyosarcoma

Sarcoma, Synovial

Neurofibrosarcoma

Sarcoma, Alveolar Soft Part

Solitary Fibrous Tumors

Hemangiopericytoma

Mesenchymoma

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Epithelioid Sarcoma

Alveolar Soft Part Sarcoma

Malignant Mesenchymoma

Radiotherapy Conventional treatment arm A total of 33 fractions each of 2Gy should be given once a day for 5 days per week over 6 weeks and 3 days in week 7, totalling 66Gy. The first 50 Gy in 25 fractions will be given to CTV1 and subsequent 16 Gy in 8 fractions will be delivered to CTV2.

Radiotherapy Research arm A total of 33 fractions each of 2Gy should be given once a day for 5 days per week over 6 weeks and 3 days in week 7, totalling 66Gy. The 66Gy in 33 fractions will be delivered to CTV2 alone. No attempt will be made to include drain/biopsy sites or the surgical scar.

radiotherapy as adjuvant treatment for adults with soft tissue sarcoma extremities

radiotherapy

Martin Robinson, MD

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving radiation therapy to a smaller area of tissue surrounding the tumor is as effective as giving radiation therapy to a wider area of tissue surrounding the tumor in treating soft tissue sarcoma.

PURPOSE: This randomized phase III trial is studying giving external-beam radiation therapy to a small area of tissue surrounding the tumor to see how well it works compared with giving external-beam radiation therapy to a wider area of tissue surrounding the tumor in treating patients who have undergone surgery for soft tissue sarcoma of the arms, hands, legs, or feet.

OBJECTIVES:

Primary

* Determine if reduced volume adjuvant radiotherapy increases limb function without compromising local control in patients with previously resected extremity soft tissue sarcoma.

Secondary

* Determine the toxicity of this regimen in these patients.
* Determine the overall level of disability in patients treated with this regimen.
* Determine the disease-free survival and overall survival of these patients.

OUTLINE: This is a randomized, controlled, prospective, multicenter study. Patients are stratified according to tumor grade (1 vs 2 vs 3), adequacy of surgical clearance (R0 vs R1), and treatment center. Patients are randomized to 1 of 2 treatment arms.

* Arm I (control): Patients undergo external beam radiotherapy (EBRT), including full margins, once daily 5 days a week for 6½ weeks .
* Arm II: Patients undergo EBRT as in arm I but only reduced margins are included.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Randomised Trial of Volume of Post-operative Radiotherapy Given to Adult Patients With eXtremity Soft Tissue Sarcoma

Randomised Trial of Post-Operative Radiotherapy Given to Adult Patients With Extremity Soft Tissue Sarcoma [VORTEX]

Sheffield Teaching Hospitals NHS Foundation Trust

Osteosarcoma

Rhabdomyosarcoma

Dermatofibrosarcoma

Dermatofibrosarcoma Protuberans

pre-operative radiation + surgery PTV will receive a total dose of 50 Gy in 25 fractions, 2 Gy per fraction, 5 fractions per week, over approximately 5 weeks. Concurrently, the GTV2, if present, will receive 54 Gy in 25 fraction. Dose will be prescribed to the isodose volume that encompasses the PTV. All patients will be treated by 6 MV photon beam.

gene expression analysis

polymerase chain reaction

western blotting

neoadjuvant therapy

therapeutic conventional surgery

intensity-modulated radiation therapy

Richard D. Pezner, MD

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying the side effects of intensity-modulated radiation therapy and to see how well it works in treating patients undergoing surgery for stage IB, stage II, or stage III soft tissue sarcoma.

OBJECTIVES:

Primary

* Estimate the wound complication rate in patients with stage IB-III soft tissue sarcoma (STS) treated with neoadjuvant intensity-modulated radiotherapy (IMRT).

Secondary

* Assess local control rate in patients treated with this regimen.
* Assess metastatic failure rate in patients treated with this regimen.
* Assess disease-free survival of patients treated with this regimen.
* Assess overall survival of patients treated with this regimen.
* Assess function and general health in these patients using the Musculoskeletal Tumor Society rating scale, Toronto Extremity Salvage Score, and the Short-Form 36.
* Determine changes in STS gene expression after IMRT by microarray analyses.
* Correlate, preliminarily, changes in STS gene expression with pathological and clinical outcomes.

OUTLINE: Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery \> 1 month after completion of IMRT.

Tumor tissue samples are collected at baseline and at the time of surgery for correlative laboratory studies. Samples are analyzed for gene expression by RNA microarray, real-time polymerase chain reaction, and western blotting.

After completion of study treatment, patients are followed periodically for 2 years.

Intensity-Modulated Radiation Therapy in Treating Patients Undergoing Surgery for Stage IB, Stage II, or Stage III Soft Tissue Sarcoma

Phase II Study of Preoperative Intensity-Modulated Radiation Therapy for Soft-Tissue Sarcomas

Major wound complications up to 4 months post surgery include:

Complications requiring a secondary operation under general or regional anesthesia for wound care.

Seroma aspiration. Drain placement. Minor wound debridement and wound care. Readmission for wound care such as intravenous antibiotics. Persistent wound deep packing or wound vacuum assisted closure for greater than 120 days.

City of Hope Medical Center

Only one patients was on treatment for 5 days with no adverse events to report.

Arm 1

Age, Categorical

Study closed 05/12/2010 (opened 7/25/2008): No patients were accrued and treated per protocol in nearly two years (2 patients were screened). The study was terminated by the IRB when the PI decided not to continue. Protocol objectives were not met.

Paul Frankel, Ph.D.

The one patient accrued to the study stopped treatment prior to completing treatment due to insurance denial.

Wound Complication Rate

Desmoplastic Small Round Cell Tumor

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Trabectedin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Doxorubicin administered on day 1 every 3 weeks for a maximum of 6 cycles

Trabectedin administered on day 1 every 3 weeks at the dose of 1.3 mg/m² until progression

Trabectedin administered on day 1 every 3 weeks at the dose of 1.5 mg/m² over 24 hours until progression

doxorubicin hydrochloride

trabectedin

laboratory biomarker analysis

quality-of-life assessment

Nguyen Binh Bui, MD

James E. Butrynski, MD

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride and trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether trabectedin is more effective than doxorubicin hydrochloride in treating patients with advanced or metastatic soft tissue sarcoma.

PURPOSE: This randomized phase II/III trial is studying the safety of trabectedin compared with doxorubicin hydrochloride and to see how well they work in treating patients with advanced or metastatic soft tissue sarcoma.

OBJECTIVES:

* To evaluate whether trabectedin given as first-line chemotherapy for patients with previously untreated advanced or metastatic malignant soft tissue sarcoma prolongs progression-free survival as compared to doxorubicin hydrochloride.
* To identify and validate biomarkers (including, but not limited to, XPG, BRCA1, RAD51, BRCA2, ATM and CHK1) of sensitivity to trabectedin in order to allow the selection of patients that benefit most from trabectedin treatment. (Optional translational research)

OUTLINE: This is a multicenter, phase IIB study followed by a phase III study. Patients are stratified according to institution, age at registration (\< 60 years old vs ≥ 60 years old), and presence of liver metastases (yes vs no).

* Phase IIB (step 1): Patients are randomized to 1 of 3 treatment arms.

  * Arm I: Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  * Arm II: Patients receive trabectedin IV over 3 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  * Arm III: Patients receive trabectedin IV continuously over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

At the end of step 1, the best regimen of trabectedin will be determined. Patients receiving the non-selected trabectedin regimen ("losing arm") are offered to cross over in order to receive the selected regimen of trabectedin.

* Phase III (step 2): Patients are randomized to 1 of 2 treatment arms.

  * Arm I: Patients receive trabectedin IV on day 1 using the preferred regimen determined in step 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  * Arm II: Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaire (EORTC QLQ-C30 version 3) at baseline, at 6, 12, 24, and 36 weeks during study, and at the end of study.

Tumor tissue block obtained at diagnosis may be analyzed to identify and validate biomarkers of sensitivity to trabectedin and for tissue microarrays.

After completion of study therapy, patients are followed up at 1 month, every 6 or 12 weeks until disease progression, and every 12 weeks thereafter.

Doxorubicin Hydrochloride or Trabectedin in Treating Patients With Previously Untreated Advanced or Metastatic Soft Tissue Sarcoma

TRUSTS: A Phase IIB/III Multicenter Study Comparing the Efficacy of TRabectedin Administered as a 3-Hour or 24-Hour Infusion to Doxorubicin in Patients With Advanced or Metastatic Untreated Soft Tissue Sarcoma

Sarcoma Alliance for Research through Collaboration

European Organisation for Research and Treatment of Cancer - EORTC

microarray analysis

molecular diagnostic method

biologic sample preservation procedure

Contact Person

Catherine West

RATIONALE: Collecting and storing samples of tumor tissue from patients with soft tissue sarcoma to test in the laboratory may help the study of cancer in the future.

PURPOSE: This laboratory is collecting tissue samples from patients with soft tissue sarcoma of the arms, hands, legs, or feet treated on clinical trial CRUK-VORTEX.

OBJECTIVES:

* Determine early in the course of treatment which patients treated on clinical trial CRUK-VORTEX have an increased likelihood of distant metastases so as to highlight individuals who might benefit from early adjuvant systemic therapy.

OUTLINE: This is a multicenter study.

Tumour and normal tissue samples will be taken at the time of surgery during treatment on clinical trial CRUK-VORTEXand preserved for future microarray analyses. Tissue microarrays will be produced from both tumor and normal tissues. Blood samples will be collected for future DNA analysis.

Tissue Sample Collection From Patients With Soft Tissue Sarcoma of the Arms, Hands, Legs, or Feet Treated on Clinial Trial CRUK-VORTEX

VORTEX-BIOBANK: Prospective Sample Collection for the VORTEX Randomised Radiotherapy Trial in Patients With Extremity Soft Tissue Sarcoma [VORTEX BIOBANK]

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Image-Guided Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Shoulder, Arm, Hip, or Leg	NCT00589121	Lymphedema Musculoskeletal... Radiation Fibro... Radiation Toxic... Sarcoma	Chemotherapy Radiation thera... Surgery	18 Years -	Radiation Therapy Oncology Group
Randomised Trial of Volume of Post-operative Radiotherapy Given to Adult Patients With eXtremity Soft Tissue Sarcoma	NCT00423618	Sarcoma	radiotherapy	16 Years - 120 Years	Sheffield Teaching Hospitals NHS Foundation Trust
Intensity-Modulated Radiation Therapy in Treating Patients Undergoing Surgery for Stage IB, Stage II, or Stage III Soft Tissue Sarcoma	NCT00740597	Sarcoma	gene expression... polymerase chai... western blottin... neoadjuvant the... therapeutic con... intensity-modul...	18 Years -	City of Hope Medical Center
Doxorubicin Hydrochloride or Trabectedin in Treating Patients With Previously Untreated Advanced or Metastatic Soft Tissue Sarcoma	NCT01189253	Sarcoma	doxorubicin hyd... trabectedin laboratory biom... quality-of-life...	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Tissue Sample Collection From Patients With Soft Tissue Sarcoma of the Arms, Hands, Legs, or Feet Treated on Clinial Trial CRUK-VORTEX	NCT00900211	Sarcoma	microarray anal... molecular diagn... biologic sample...	16 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for adult extraskeletal chondrosarcoma