A Phase II Clinical Trial Evaluating the Efficacy and Safety of Sintilimab for Advanced Rare Cancers (SiARa Cancer Study) - Undifferentiated Pleomorphic Sarcoma (SiARa-UPS)
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab
- Conditions
- Locally Advanced Undifferentiated Pleomorphic Sarcoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Best Overall Response Rate
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This phase II trial investigates the effects of sintilimab in treating patients with undifferentiated pleomorphic sarcoma that has spread to nearby tissue or lymph nodes (locally advanced), spread to other places in the body (metastatic), come back (recurrent), or cannot be removed by surgery (unresectable). 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.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the efficacy of sintilimab in subjects with undifferentiated pleomorphic sarcoma (UPS) (overall response rate \[ORR\] at 12 weeks \[12W\] by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1). SECONDARY OBJECTIVE: I. To evaluate the ORR (RECIST 1.1) and disease control rate (DCR), PFS, overall survival (OS), safety and duration of response (DOR) of sintilimab in subjects with UPS. EXPLORATORY OBJECTIVES: I. To evaluate the correlation between biomarkers in tumor tissue and efficacy, including but not restricted to PD-L1 expression level, tertiary lymphoid structures (TLS) 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), identification/quantification of immunologic changes, and cytokine analyses. OUTLINE: Patients receive sintilimab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 60 days for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histopathologically confirmed unresectable, locally advanced, recurrent or metastatic UPS
- •Refractory or intolerant to at least one line of systemic chemotherapy. Patient ineligible for cytotoxic chemotherapy are eligible
- •Aged \>= 18
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- •Subject must be unsuitable for definitive treatment, such as definitive chemoradiotherapy and/or surgery
- •Could provide archival or fresh tissues for correlative analysis
- •Have at least one measurable lesion as per RECIST version (v)1.1
- •Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
- •Note: Subjects cannot receive blood transfusion, erythropoietin (EPO), or granulocyte-colony stimulating factor (GSF) within 7 days prior to the blood collection
- •Platelet (PLT) count \>= 75 x 10\^9/L
Exclusion Criteria
- •Received treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug that specifically targets T-cell co-stimulation or immune checkpoint pathways
- •Enrolled in another interventional clinical study, unless only involved in an observational study (non-interventional) or in the follow-up phase of an interventional study
- •Received palliative therapy for local lesion within 2 weeks prior to the first dose
- •Received systemic treatment with anti-cancer indications or immunomodulators (including thymosins, interferons, and interleukins) within 2 weeks prior to the first dose of study treatment
- •Received systemic immunosuppressants within 2 weeks prior to first dose, excluding local use of glucocorticoids administered by nasal, inhaled, or other routes, and systemic glucocorticoids at physiological doses (no more than 10 mg/day of prednisone or equivalents), or glucocorticoids to prevent allergies to contrast media
- •Received a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or be scheduled to receive live attenuated vaccine during the study period.
- •Note: Seasonal inactivated influenza virus vaccines within 4 weeks prior to the first dose of study treatment are permitted, but attenuated influenza vaccines are not
- •Received major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment or is scheduled to receive major surgery during the course of the trial
- •Any toxicity (excluding alopecia, events that are not clinically significant, or asymptomatic laboratory abnormalities) due to prior anti-tumor therapy that has not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 grade 0 or 1 prior to the first dose of study treatment
- •Known symptomatic central nervous system (CNS) metastasis or carcinomatous meningitis. Subjects with brain metastases who have received prior treatment can be enrolled if the disease is stable (no imaging evidence of progressive disease (PD) for at least 4 weeks prior to the first dose of study treatment), there is no evidence of new brain metastases or progression of the existing metastatic lesion(s) upon repeated imaging, and corticosteroids have not been required for at least 14 days prior to the first dose of study treatment. Patients with carcinomatous meningitis are ineligible, regardless of whether the disease is clinically stable or not
Arms & Interventions
Treatment (sintilimab)
Patients receive sintilimab IV over 30-60 minutes on day 1. Cycles repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
Intervention: Sintilimab
Outcomes
Primary Outcomes
Best Overall Response Rate
Time Frame: At 12 weeks
Will be defined as the proportion of subjects with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1) in the evaluable population.