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

Osteosarcoma

Hemangiosarcoma

Neoplasms, Bone Tissue

Neoplasms, Vascular Tissue

Durvalumab

Immunoglobulin G

Immunoglobulins, Intravenous

Immunologic Factors

Patients receive oleclumab IV over 1 hour every 2 weeks for 5 doses, then every 4 weeks thereafter. Patients also receive durvalumab IV over 1 hour every 4 weeks. Cycle repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Oleclumab

Neeta Somaiah

This phase II trial investigates how well oleclumab and durvalumab work in treating patients with sarcoma that has come back (recurrent) or does not respond to treatment (refractory) or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as oleclumab and durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To estimate the tumor response (Response Evaluation Criteria in Solid Tumors \[RECIST\]) at 4 months in patients with relapsed/refractory sarcoma. (Cohorts 1 and 2) II. To determine the event-free survival (EFS) rate at 4 months after initiation of the treatment in patients with relapsed/refractory osteosarcoma receiving novel immunotherapeutic agents. (Cohort 3)

SECONDARY OBJECTIVES:

I. To determine the progression-free survival (PFS) rate at 12 weeks after initiation of the treatment in patients with relapsed/refractory sarcoma receiving novel immunotherapeutic agents.

II. To estimate the tumor response (Immune-related Response Criteria \[irRC\] and RECIST) in patients with relapsed/refractory sarcoma.

III. To evaluate the safety and tolerability of receiving novel immunotherapeutic agents in patients with relapsed/refractory sarcoma.

IV. To estimate the median PFS and overall survival (OS) in patients with relapsed/refractory sarcoma receiving novel immunotherapeutic agents.

EXPLORATORY OBJECTIVES:

I. To determine expression of biomarkers (including but not limited to CD73, PD-1 and PD-L1) in pre \& post treatment (tx) samples.

II. Quantification and characterization of the immune infiltrate (and other histologic and immunohistologic changes) from tissue samples prior to treatment initiation and post treatment (biopsy at week 6).

III. Identification/quantification of immunologic changes (CD4+, CD8+, Teff, Treg cells and NK cells) in peripheral blood.

IV. Determining an immunoscore based on baseline tumor sample (identification of molecular response/resistance patterns/future therapy options).

OUTLINE:

Patients receive oleclumab intravenously (IV) over 1 hour every 2 weeks for 5 doses, then every 4 weeks thereafter. Patients also receive durvalumab IV over 1 hour every 4 weeks. Cycle repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 3 months for up to 5 years.

Oleclumab and Durvalumab for the Treatment of Recurrent, Refractory, or Metastatic Sarcoma

A Phase II Multi-Arm Study to Test the Efficacy of Oleclumab and Durvalumab in Multiple Sarcoma Subtypes

Evaluated using immunohistochemistry (CD73, PD-1/PD-L1) expression analysis). Exploratory data analysis and graphical methods will be applied to examine the distribution of the biomarker data, error checking, and outlier identification. T-test/analysis of variance (ANOVA) or their nonparametric counterparts, Wilcoxon rank-sum test/Kruskal-Wallis test will be used to detect differences of the biomarkers between groups. Linear mixed effect models for repeated measures analysis (Liang, 1986) will be employed to assess the change in biomarkers over time with multi-covariates including disease characteristics (tumor stage, site, pathology), and other prognostic factors. Appropriate transformation of the outcome assessment values will be used to satisfy the normality assumption of linear mixed effect model.

Evaluated using immunofluorescence analysis. Exploratory data analysis and graphical methods will be applied to examine the distribution of the biomarker data, error checking, and outlier identification. T-test/ANOVA or their nonparametric counterparts, Wilcoxon rank-sum test/Kruskal-Wallis test will be used to detect differences of the biomarkers between groups. Linear mixed effect models for repeated measures analysis (Liang, 1986) will be employed to assess the change in biomarkers over time with multi-covariates including disease characteristics (tumor stage, site, pathology), and other prognostic factors. Appropriate transformation of the outcome assessment values will be used to satisfy the normality assumption of linear mixed effect model.

Evaluated using flow cytometry analysis. Exploratory data analysis and graphical methods will be applied to examine the distribution of the biomarker data, error checking, and outlier identification. T-test/ANOVA or their nonparametric counterparts, Wilcoxon rank-sum test/Kruskal-Wallis test will be used to detect differences of the biomarkers between groups. Linear mixed effect models for repeated measures analysis (Liang, 1986) will be employed to assess the change in biomarkers over time with multi-covariates including disease characteristics (tumor stage, site, pathology), and other prognostic factors. Appropriate transformation of the outcome assessment values will be used to satisfy the normality assumption of linear mixed effect model.

Defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Defined as the time from enrollment to disease progression, death, or discontinuation of treatment for any reason (for example toxicity, patient preference, or initiation of new treatment without documented disease progression). Defined by RECIST 1.1. Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analysis of survival data based on the Cox proportional hazards model will be conducted. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure the models are appropriate.

Defined as the time from treatment onset to either disease progression as defined by RECIST 1.1. Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analysis of survival data based on the Cox proportional hazards model will be conducted. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure the models are appropriate.

Defined by Immune-related Response Criteria (irRC) and RECIST.

Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicity data by grade and relationship with the treatment by cohorts and 3 cohorts combined, will be summarized by frequency tables. For the toxicity endpoint, per-treated analysis will be used to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received. Toxicity rate will be estimated with 95% confidence interval.

Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analysis of survival data based on the Cox proportional hazards model will be conducted. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure the models are appropriate.

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Adenosine

Participants will have a diagnosis of recurrent or metastatic Dedifferentiated Liposarcoma/DDLPS

Will be administered PO daily for 24 weeks

Etrumadenant

Will be administered IV every 2 weeks for 24 weeks

Zimberelimab

Evan Rosenbaum, MD

Sujana Movva, MD

William Tap, MD

Participants will have a diagnosis of dedifferentiated liposarcoma (DDLS) that has spread beyond its original location (advanced). In addition, their DDLS either has come back after treatment (recurrent), has spread to different parts of your body (metastatic), or is unable to be removed surgically (unresectable). The purpose of this study is to find out whether the combination of etrumadenant and zimberelimab is an effective treatment for people with advanced DDLS.

A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma

A Phase II Study of Adenosine Receptor (A2A and A2B) Inhibition (AB928) in Combination With Anti-PD-1 Therapy (AB122) in Patients With Advanced Dedifferentiated Liposarcoma

To estimate the overall response rate (CR + PR per RECIST 1.1) to etrumadenant combined with zimberelimab at 24 weeks in patients with advanced Dedifferentiated Liposarcoma/DDLPS

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
Oleclumab and Durvalumab for the Treatment of Recurrent, Refractory, or Metastatic Sarcoma	NCT04668300	Metastatic Angi... Metastatic Dedi... Metastatic Oste... Recurrent Angio... Recurrent Dedif... Recurrent Osteo... Refractory Dedi... Refractory Oste...	Durvalumab Oleclumab	12 Years -	M.D. Anderson Cancer Center
A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma	NCT05886634	Dedifferentiate... Soft Tissue Sar... Sarcoma,Soft Ti... Sarcoma Recurrent Dedif... Unresectable De... Metastatic Dedi...	Etrumadenant Zimberelimab	18 Years -	Memorial Sloan Kettering Cancer Center
A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma	NCT05886634	Dedifferentiate... Soft Tissue Sar... Sarcoma,Soft Ti... Sarcoma Recurrent Dedif... Unresectable De... Metastatic Dedi...	Etrumadenant Zimberelimab	18 Years -	Memorial Sloan Kettering 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

Spots Global Cancer Trial Database for recurrent dedifferentiated liposarcoma