A Phase 2 Clinical Trial Evaluating the Efficacy and Safety of Sintilimab for Angiosarcoma
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab
- Conditions
- Locally Advanced Angiosarcoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Progression-free rate
- Status
- Terminated
- Last Updated
- 8 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histopathologically confirmed unresectable, locally advanced, recurrent or metastatic angiosarcoma
- •Intolerant to or progressed on at least one line of systemic chemotherapy. Patient ineligible for cytotoxic chemotherapy are eligible
- •Aged \>= 18
- •Can provide archival or fresh tissues for optional correlative analysis
- •Have at least one measurable lesion as per RECIST version (v)1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
- •Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
- •Platelet (PLT) count \>= 75 x 10\^9/L
- •Hemoglobin (HGB) \>= 8.0 g/dL
- •Total bilirubin (TBIL) =\< 1.5 x upper limit of normal (ULN)
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 for angiosarcoma, unless only involved in an observational study (non-interventional) or in the follow-up phase of an interventional study
- •Received palliative radiation 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 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.
Intervention: Sintilimab
Treatment (sintilimab)
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.
Intervention: Quality-of-Life Assessment
Outcomes
Primary Outcomes
Progression-free rate
Time Frame: At 9 cycles (1 cycle = 21 days)
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.
Secondary Outcomes
- Duration of response(From first date of investigator-determined response to investigator-determined progressive disease (PD) or death in the subjects who have achieved complete response (CR) or partial response (PR), assessed up to 5 years)
- Progression free survival(From treatment onset to either disease progression as defined by RECIST or death from any cause, or discontinuation of treatment for any reason, whichever occurs first, assessed up to 5 years)
- Overall survival(From treatment onset to death, assessed up to 5 years)
- Incidence of adverse events (AEs)(Up to 90 days after completion of treatment)
- Objective response rate (complete response + partial response)(Up to 5 years)
- Stable disease rate(Up to 5 years)