Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Osteosarcoma

Sarcoma

Liposarcoma

Hemangiosarcoma

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Adipose Tissue

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

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.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Patients receive sintilimab IV over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue to receive treatment at the discretion of the treating physician.

Quality-of-Life Assessment

Sintilimab

Vinod Ravi

This phase II trial evaluates the effect of sintilimab in treating patients with angiosarcoma that has spread to nearby tissue or lymph nodes (locally advanced), has spread to other places in the body (metastatic), or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as sintilimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sintilimab may help to control angiosarcoma.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of sintilimab in subjects with angiosarcoma (progression- free rate PFR at 9 cycles by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1).

SECONDARY OBJECTIVE:

I. To evaluate the objective response rate (ORR), stable disease rate (SDR), progression free survival (PFS), overall survival (OS), quality of life (QOL), safety and duration of response (DOR) of sintilimab in subjects with angiosarcoma.

EXPLORATORY OBJECTIVES:

I. To evaluate the correlation between biomarkers in tumor tissue and efficacy, including but not restricted to PD-L1 expression level, transcriptome sequencing, single-cell sequencing, and multicolor immunohistochemistry (IHC) analyses.

II. To evaluate the correlation between biomarkers in peripheral blood and efficacy, including but not restricted to soluble PD-L1, circulating tumor deoxyribonucleic acid (DNA) (ctDNA), and cytokine analyses.

OUTLINE:

Patients receive sintilimab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue to receive treatment at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 30 and 90 days, and then every 60 days for up to 3 years.

Sintilimab for the Treatment of Locally Advanced, Metastatic, or Recurrent Angiosarcoma, the SiARa Cancer Study

A Phase 2 Clinical Trial Evaluating the Efficacy and Safety of Sintilimab for Angiosarcoma

Defined as the proportion of subjects with no confirmed progressive disease (PD) at 9 cycles assessed by the independent radiology review based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1) in the evaluable population.

Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analyses 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 that the models are appropriate.

Corresponding exact 95% confidence intervals (CIs) will be estimated using binomial distribution.

Defined as stable disease for 9 cycles (1 cycle = 21 days). Corresponding exact 95% CIs will be estimated using binomial distribution.

The incidence (frequency) of AEs, treatment-emergent (TE)AEs, treatment-related (TR)AEs, immunity related (ir)AEs, serious AEs, AEs resulting in treatment discontinuation, and AEs resulting in death will be summarized. The severity distribution of TEAEs, TRAEs, and irAEs will be summarized using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Sintilimab for the Treatment of Locally Advanced, Metastatic, or Recurrent Angiosarcoma, the SiARa Cancer Study	NCT05026736	Locally Advance... Metastatic Angi... Recurrent Angio...	Quality-of-Life... Sintilimab	18 Years -	M.D. Anderson Cancer Center
Sintilimab for the Treatment of Locally Advanced, Metastatic, or Recurrent Angiosarcoma, the SiARa Cancer Study	NCT05026736	Locally Advance... Metastatic Angi... Recurrent Angio...	Quality-of-Life... Sintilimab	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for recurrent angiosarcoma