Neoplasms

All Conditions

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Patients undergo hypofractionated radiation therapy QD (except weekends and holidays) over 3 weeks for a total of 15 fractions. Within 3-6 weeks after completion of radiation therapy, patients undergo surgical resection.

Undergo hypofractionated radiation therapy

Hypofractionated Radiation Therapy

Quality-of-Life Assessment

Questionnaire Administration

Resection

Safia K. Ahmed, M.D.

This phase II trial investigates the effects of hypofractionated radiation therapy before surgery on wound complications associated with surgery in treating patients with soft tissue sarcoma of the extremity (arms, hands, legs or feet) and superficial trunk that has not spread to other parts of the body (localized) and can be removed by surgery (resectable). Hypofractionated is a shorter radiation therapy treatment length (fewer radiation treatment days) and administers the total radiation dose as larger daily doses, compared to conventionally fractionated therapy.

PRIMARY OBJECTIVE:

I. To report the major acute wound complication rate associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

SECONDARY OBJECTIVES:

I. To report the 5-year local failure rate associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

II. To report the 5-year disease-free survival rate associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

III. To report the 5-year overall survival rate associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

IV. To report long-term toxicity rates associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

V. To describe patterns of relapse associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

VI. To describe patient reported outcomes/quality-of-life outcomes with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

OUTLINE:

Patients undergo hypofractionated radiation therapy once daily (QD) (except weekends and holidays) over 3 weeks for a total of 15 fractions. Within 3-6 weeks after completion of radiation therapy, patients undergo surgical resection.

After completion of study treatment, patients are followed up at 4-8 weeks, every 3-4 months for years 1-2, and every 6 months for years 3-5.

Radiation Therapy Before Surgery for Localized, Resectable Soft Tissue Sarcoma of the Extremity and Superficial Trunk

A Phase II Study of Hypofractionated Pre-Operative Radiation Therapy for Localized, Resectable Soft Tissue Sarcoma of the Extremity and Superficial Trunk

Will be estimated by the number of patients who experience the major wound complications within 120 days following surgery divided by the total number of evaluable patients. Major wound complication is defined as secondary unplanned operation under general or regional anesthesia for wound repair (e.g.,debridement, operative drainage, or secondary wound closure including rotationplasty, free flaps or skin grafts); or wound management without secondary operation including invasive procedures (e.g., aspiration of seroma or readmission for wound care such as intravenous antibiotics or persistent deep packing for 120 days or longer). 95% confidence intervals using normal approximation to binomial wound complication proportion will be calculated.

Will be defined any radiographic or pathologic evidence of recurrent disease inside the clinical target volume (CTV) and/ or to within 3 cm from the edge of the CTV. Local failure rate at 5 years (LFR5) will be evaluated by the number of patients free of local failure/recurrence at 5 year divided by the total number of evaluable patients. Exact binomial 95% confidence interval for the point estimate will be provided. In the case of censoring prior to 5 years, LFR5 will be estimated using the Kaplan-Meier method.

The distribution of disease-free survival will be estimated using method of Kaplan-Meier.

The distribution of overall survival will be estimated using method of Kaplan-Meier.

The descriptions and grading scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for adverse event reporting. The rate of \>= grade 2 late adverse events will be estimated by the number of patients with a \>= grade 2 late adverse event divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true rate of \>= grade 2 late adverse events will be calculated.

Pattern of relapse will be evaluated by number of patients with patterns of tumor recurrence such as local recurrence, marginal recurrence, regional recurrence, distant metastasis, and second primary tumor divided by the total number of evaluable patients. Exact binomial 95% confidence interval for the point estimate will be provided.

The descriptions and grading scales found in the revised NCI CTCAE version 5.0 will be utilized for adverse event reporting. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Results from the ten-item Patient Reported Outcomes Measurement Information System (PROMIS-10) questionnaire will be used to evaluate physical and mental health separately. The Wilcoxon signed-rank test will be utilized to assess changes in raw PROMIS scores. Mean change, along with standard deviation will be reported. The PROMIS-10 consists of ten items that measure physical health, physical functioning, general mental health, emotional distress, satisfaction with social activities and relationships, ability to carry out usual social activities and roles, pain, fatigue and overall quality of life.

Results from the Toronto Extremity Salvage Score (TESS) questionnaire will be used to evaluate functional outcomes. Mean change from baseline to 24 months post-surgery, along with standard deviation will be reported by version. The TESS was designed as a measure of the difficulty patients have performing routine daily activities. It consists of 31 items with responses from 1 (impossible to do) to 5 (not at all difficult).

Mayo Clinic

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Ichthyosis, X-Linked

Patients receive hypofractionated radiation therapy in 15 daily fractions over 3 weeks in the absence of disease progression or unacceptable toxicity.

Beverly A Guadagnolo

This phase II trial studies the wound complication risk of shorter course, hypofractionated pre-surgery radiation therapy in treating patients with localized soft tissue sarcoma of the extremity of superficial trunk that can be removed by surgery. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Shorter course hypofractionated pre surgery radiation therapy may be more convenient for patients with soft tissue sarcoma than a longer course of radiation therapy, and may result in fewer complications.

PRIMARY OBJECTIVES:

I. To determine, in patients with localized, resectable soft tissue sarcoma, whether there is a non-inferior major wound complication rate for patients receiving 42.75 Gy in 15 fractions over 3 weeks compared to historical controls who received 50 Gy in conventional fractionation over 5-6 weeks.

SECONDARY OBJECTIVES:

I. To determine whether local control rates among patients treated with 42.75 Gy in 15 fractions is similar to that observed in previous studies for patients treated with 50 Gy in conventional fractionation over 5-6 weeks.

II. To determine whether patterns of local relapse, relapse free survival, overall survival, or metastatic disease free survival for patients treated with 42.75 Gy in 15 fractions are similar to previously reported studies.

III. To determine where there is a difference in pathologic response in tumor specimens treated with 42.75 Gy in 15 fractions compared to previously reported rates of hyalinization, fibrosis, or necrosis.

IV. To explore quality of life, as measured by the Functional Assessment of Cancer Therapy-General (FACT-G), financial toxicity as measured by the Comprehensive Score for financial Toxicity (COST) Instrument, and patient reported outcomes, as measured by the Toronto Extremity Salvage Score (TESS), among individuals undergoing a shorter, hypofractionated course of pre-operative radiation therapy for soft tissue sarcoma of the extremity or superficial trunk.

V. To gather subjective data on patient treatment preferences and experiences among individuals undergoing a shorter, hypofractionated course of pre-operative radiation therapy for soft tissue sarcoma of the extremity or superficial trunk.

OUTLINE:

Patients receive hypofractionated radiation therapy in 15 daily fractions over 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-4 months for 2 years, every 6 months for 3 years, and then every year for up to 10 years.

Shorter Course, Hypofractionated Pre-Surgery Radiation Therapy in Treating Patients With Localized, Resectable Soft Tissue Sarcoma of the Extremity of Superficial Trunk

Prospective Trial of Hypofractionated Pre-Operative Radiation Therapy for Localized, Resectable Soft Tissue Sarcoma of the Extremity or Superficial Trunk (HYPORT-STS)

A Bayesian approach for the analysis of a stopping rule of higher acute wound complications for the new dose (E) will be employed.

The data from long-term follow-up will be analyzed for the local recurrence free survival. Kaplan-Meier curves will be generated of survival estimates. We will compare these to historical controls.

The data from long-term follow-up will be analyzed for disease-free survival. Kaplan-Meier curves will be generated of survival estimates. Will compare these to historical controls.

Kaplan-Meier curves will be generated of survival estimates.

Acute toxicity will be documented and rates tabulated.

Late radiation toxicity will be documented and rates tabulated.

Limb function and overall patient quality of life/functional status will be documented according to the Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage Score (TESS) and Euroqol-5D (EQ5D), which will be summarized and analyzed as a continuous variable. Differences between mean scores will be tested using the Mann-Whitney test. Mean and median and their 95% confidence interval (CI) will be presented.

Limb function and overall patient quality of life/functional status will be documented according to the MSTS and TESS and Euroqol-5D (EQ5D), which will be summarized and analyzed as a continuous variable. Differences between mean scores will be tested using the Mann-Whitney test. Mean and median and their 95% CI will be presented.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Nervous System Diseases

Liposarcoma

Histiocytoma, Malignant Fibrous

Fibrosarcoma

Histiocytoma

Histiocytoma, Benign Fibrous

Leiomyosarcoma

Rhabdomyosarcoma

Sarcoma, Synovial

Nerve Sheath Neoplasms

Neurofibrosarcoma

Myosarcoma

Neoplasms, Adipose Tissue

Neoplasms, Connective Tissue

Neoplasms, Nerve Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neoplasms, Fibrous Tissue

Neurofibromatoses

Neurofibroma

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Neurofibromatosis

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Nivolumab

Poly I-C

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive BO-112 intratumorally on days 8 and 15 or 1, 8, and 15 and nivolumab IV over 30-60 minutes on day 8 in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy on days 8-12 for a total of 5 fractions. Patients then undergo standard of care definitive surgical resection on day 26 to 50.

Definitive Surgical Resection

Nanoplexed Poly I:C BO-112

Radiation Therapy

Vishruth Reddy, MD, PhD

This phase I trial studies the side effects of BO-112 when given together with nivolumab before surgery in treating patients with soft tissue sarcoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with BO-112, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab and BO-112 before surgery may work better in treating patients with soft tissue sarcoma compared to nivolumab alone.

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of integrating BO-112, and BO-112 with nivolumab in soft tissue sarcoma patients undergoing preoperative radiotherapy.

SECONDARY OBJECTIVES:

I. Determine the change in T cell infiltration at surgical resection from baseline as measured by immunohistochemistry.

II. Assess treatment effect (necrosis score) of BO-112 and BO-112 in combination with nivolumab in soft tissue sarcoma patients receiving preoperative hypofractionated radiotherapy, compared to patients treated on a recently completed phase 2 study of preoperative hypofractionated radiotherapy alone.

III. Evaluate the 2-year rate of local and distant metastasis of BO-112 and BO-112 in combination with nivolumab in patients with localized resectable soft tissue sarcoma receiving preoperative hypofractionated radiotherapy, as compared to historical patients receiving preoperative radiotherapy alone.

EXPLORATORY OBJECTIVES:

I. Evaluate the dynamics of the intratumoral T cell phenotype. II. Assess the capacity to grow ex vivo tumor infiltrating lymphocytes from patients treated with BO-112 and BO-112 in combination with nivolumab.

III. Analyze changes in T-cell receptor (TCR) repertoire in tumor infiltrating lymphocytes and peripheral blood mononuclear cells (PBMCs) between baseline, post-treatment, and ex vivo cultured tumor infiltrating lymphocyte (TIL) samples.

IV. For patients with disease burden outside of the resected lesion, assess imaging response to treatment using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

OUTLINE:

Patients receive BO-112 intratumorally on days 8 and 15 or 1, 8, and 15 and nivolumab intravenously (IV) over 30-60 minutes on day 8 in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy on days 8-12 for a total of 5 fractions. Patients then undergo standard of care definitive surgical resection on day 26 to 50.

After completion of study treatment, patients are followed up at 2 weeks, 3 months, and between 6-12, 12-18, and 18-24 months.

Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma

A Phase I Study of Nivolumab and Intratumoral BO 112 for Resectable Soft Tissue Sarcoma

AEs will be tabulated by type, severity, and the proportion of subject experiencing the event.

Statistical analysis of immune-oncologic changes will be performed by comparing results from surgical specimens with baseline biopsy specimens. For immunohistochemical parameters, the percentage of CD4+ (cluster of differentiation 4) or CD8+((cluster of differentiation 8) cells will be compared between biopsy and surgical specimens using a paired two-tailed ratio T-test comparing means.

Will be compared to historical samples receiving preoperative radiotherapy alone. Will use a two-sample paired T-test comparing means.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiation Therapy Before Surgery for Localized, Resectable Soft Tissue Sarcoma of the Extremity and Superficial Trunk	NCT04562480	Resectable Soft... Stage I Soft Ti... Stage IA Soft T... Stage IB Soft T... Stage II Soft T...	Hypofractionate... Quality-of-Life... Questionnaire A... Resection	18 Years -	Mayo Clinic
Shorter Course, Hypofractionated Pre-Surgery Radiation Therapy in Treating Patients With Localized, Resectable Soft Tissue Sarcoma of the Extremity of Superficial Trunk	NCT03819985	Resectable Soft... Stage I Soft Ti... Stage IA Soft T... Stage IB Soft T... Stage II Soft T... Stage III Soft ... Stage IIIA Soft... Stage IIIB Soft...	Hypofractionate... Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma	NCT04420975	Leiomyosarcoma Malignant Perip... Myxofibrosarcom... Pleomorphic Rha... Resectable Dedi... Resectable Soft... Resectable Undi... Soft Tissue Fib... Spindle Cell Sa... Stage I Retrope... Stage I Soft Ti... Stage IA Retrop... Stage IA Soft T... Stage IB Retrop... Stage IB Soft T... Stage II Retrop... Stage II Soft T... Stage III Retro... Stage III Soft ... Stage IIIA Retr... Stage IIIA Soft... Stage IIIB Retr... Stage IIIB Soft... Storiform-Pleom... Synovial Sarcom... Undifferentiate... Undifferentiate... Undifferentiate... Undifferentiate... Undifferentiate...	Definitive Surg... Nanoplexed Poly... Nivolumab Radiation Thera...	18 Years -	Jonsson Comprehensive Cancer Center
Radiation Therapy Before Surgery for Localized, Resectable Soft Tissue Sarcoma of the Extremity and Superficial Trunk	NCT04562480	Resectable Soft... Stage I Soft Ti... Stage IA Soft T... Stage IB Soft T... Stage II Soft T...	Hypofractionate... Quality-of-Life... Questionnaire A... Resection	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for stage i soft tissue sarcoma of the trunk and extremities ajcc v8