Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Gland and Hormone Related Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Sarcoma

Histiocytoma, Malignant Fibrous

Liposarcoma

Histiocytoma

Disorders of Sex Development

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Congenital Abnormalities

Urogenital Abnormalities

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Gonadal Disorders

Endocrine System Diseases

Neoplasms, Adipose Tissue

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Nivolumab

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over 1 hour on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 43.

Patients receive nivolumab as in Arm A. Patients also receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 43.

Patients receive nivolumab IV over 1 hour on days 1, 15, 29, and 43. Patients also undergo RT QD for 5 days during days 15-47 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 71.

Patients receive nivolumab as in Arm C, ipilimumab as in Arm B, and RT as in Arm C in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 71.

Radiation Therapy

Christina L Roland

This phase II trial studies how well nivolumab with and without ipilimumab and radiation therapy when given before surgery works in treating patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma that can be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab, ipilimumab, and radiation therapy may work better in treating patients with undifferentiated pleomorphic sarcoma.

PRIMARY OBJECTIVES:

I. To assess the pathologic response of nivolumab monotherapy and nivolumab and ipilimumab combination therapy administered in the neoadjuvant setting with and without radiation in patients with treatment-naive primary or locally recurrent resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

SECONDARY OBJECTIVES:

I. To assess the change in percent viable tumor cells, percent hyalinization and necrosis, proliferation by phosphohistone H3 in biopsy specimens obtained at baseline and on treatment and surgical specimens.

II. To assess the change in immune infiltrate in response to neoadjuvant nivolumab monotherapy and neoadjuvant nivolumab and ipilimumab combination therapy in patients with resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

III. To assess the objective response rate (ORR) of nivolumab monotherapy and nivolumab and ipilimumab combination therapy administered in the neoadjuvant setting as assessed by imaging (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 and Immune Related Response Criteria \[irRC\]) in patients with resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

IV. To assess the 12- and 24-month recurrence-free survival (RFS) and overall survival (OS) of patients with resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma treated with neoadjuvant nivolumab monotherapy or nivolumab and ipilimumab combination therapy.

V. To evaluate the safety of nivolumab monotherapy and combination ipilimumab and nivolumab in the neoadjuvant setting and peri-operatively by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria.

EXPLORATORY OBJECTIVES:

I. To identify immunologic and genomic markers correlating with clinical response to nivolumab monotherapy and ipilimumab with nivolumab combination therapy.

II. To assess the quality of life of patients with dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma undergoing neoadjuvant immunotherapy followed by surgical resection.

III. To analyze the microbiome to determine the role of the microbiome on development and response to therapy.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM A: Patients receive nivolumab intravenously (IV) over 1 hour on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 43.

ARM B: Patients receive nivolumab as in Arm A. Patients also receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 43.

ARM C: Patients receive nivolumab IV over 1 hour on days 1, 15, 29, and 43. Patients also undergo radiation therapy (RT) once daily (QD) for 5 days during days 15-47 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 71.

ARM D: Patients receive nivolumab as in Arm C, ipilimumab as in Arm B, and RT as in Arm C in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 71.

After completion of study treatment, patients are followed up at 6 and 18 weeks and then every 3 months for up to 2 years.

Nivolumab With and Without Ipilimumab and Radiation Therapy in Treating Patients With Recurrent or Resectable Undifferentiated Pleomorphic Sarcoma or Dedifferentiated Liposarcoma Before Surgery

Phase II Study of Neoadjuvant Checkpoint Blockade in Patients With Surgically Resectable Undifferentiated Pleomorphic Sarcoma and Dedifferentiated Liposarcoma

Pathologic response will be assessed at time of surgical resection by percentage hyalinization. The study will estimate the difference of the pathologic response between the treatment arms (A versus \[vs\] B, C vs D) along with the estimate of variation of the difference. Given the longitudinal nature of the data, linear mixed effect models for longitudinal measures will be employed to assess the change in the magnitude of the measures over time adjusting for multiple covariates including patient's characteristics, and tumor characteristics. Appropriate transformation of the outcome assessment values will be used to satisfy the normality assumption of linear mixed effect model.

Subjects will be assessed with computed tomography (CT) or magnetic resonance imaging (MRI) at screening, after completion of neoadjuvant therapy and during the post-treatment follow-up period. Baseline biopsies and blood for genomic and immunologic analyses will be obtained from patients in each group. Secondary histologic outcomes include percent viable tumor cells, percent tumor necrosis, amount of fibrosis and proliferation by phosphohistone H3.

Immune infiltrate to be assessed by analyzing changes in the immune infiltrate in biopsy specimens obtained at baseline and on-treatment, and surgical specimens in response to therapy.

Safety will be evaluated by clinical assessments including vital signs and complete physical examinations, chemistry and hematology laboratory values and formal assessments of adverse events (AEs).

Subjects will be assessed with CT or MRI at screening, after completion of neoadjuvant therapy and during the post-treatment follow-up period.

Subjects will be assessed with computed tomography (CT) or magnetic resonance imaging (MRI) at screening, after completion of neoadjuvant therapy and during the post-treatment follow-up period. Safety will be evaluated by clinical assessments including vital signs and complete physical examinations, chemistry and hematology laboratory values and formal assessments of adverse events (AEs).

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Nervous System Diseases

Fibrosarcoma

Histiocytoma, Benign Fibrous

Leiomyosarcoma

Rhabdomyosarcoma

Sarcoma, Synovial

Nerve Sheath Neoplasms

Neurofibrosarcoma

Myosarcoma

Neoplasms, Nerve Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neurofibromatoses

Neurofibroma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Neurofibromatosis

Anti-Infective Agents

Poly I-C

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

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.

Highlight Therapeutics

Jonsson Comprehensive Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab With and Without Ipilimumab and Radiation Therapy in Treating Patients With Recurrent or Resectable Undifferentiated Pleomorphic Sarcoma or Dedifferentiated Liposarcoma Before Surgery	NCT03307616	Dedifferentiate... Recurrent Dedif... Recurrent Undif... Resectable Dedi... Resectable Undi... Undifferentiate...	Ipilimumab Nivolumab Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Nivolumab With and Without Ipilimumab and Radiation Therapy in Treating Patients With Recurrent or Resectable Undifferentiated Pleomorphic Sarcoma or Dedifferentiated Liposarcoma Before Surgery	NCT03307616	Dedifferentiate... Recurrent Dedif... Recurrent Undif... Resectable Dedi... Resectable Undi... Undifferentiate...	Ipilimumab Nivolumab Radiation Thera...	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

Spots Global Cancer Trial Database for resectable dedifferentiated liposarcoma