A Single-arm, Single-center Prospective Study of Anlotinib Hydrochloride and Toripalimab in Subjects With Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma Patients
Overview
- Phase
- Phase 2
- Intervention
- Anlotinib
- Conditions
- Soft Tissue Sarcomas
- Sponsor
- Di Wu
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Rate of Participants Achieving 3-Month Progression-Free Survival (PFS)
- Last Updated
- 6 years ago
Overview
Brief Summary
The investigators hypothesize that combination anlotinib with toripalimab will improve progression-free survival relative to historical controls in patients with Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma.
Detailed Description
This is a single-institution, open-label, single-arm Phase II study to determine the efficacy and safety of anlotinib in combination with Toripalimab compared with historical controls as first-line treatment in patients with Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma. Since the primary endpoint is survival outcome, progression-free survival (PFS) sample size calculation is based on a single-arm survival design. The investigators will employ early stopping rules for lack of efficacy, based on previously reported historical controls progression-free rate at 3 months was 57% in MFH and This study predicts that as the First-Line treatment of Undifferentiated Pleomorphic Sarcoma, progression-free rate at 3 months is expected to reach more than 80%. Patients will be treated with once a day dosing of anlotinib alone for the first 7 days, followed by concurrent anlotinib administered once a day at 12mg orally (PO), plus intravenous administration of toripalimab every 21 days. Patients will be assessed every six weeks for toxicity. After the first five patients are enrolled, the investigators will assess safety of the combination. If 2 or fewer patients exhibit dose-limiting toxicity (DLT), the investigators will then proceed with intrapatient titration of anlotinib dosing at each cycle based on the presence or absence of predefined toxicities. Correlative studies characterizing T-cells in tumor tissue and in peripheral blood will be performed at three timepoints: 1. pre-treatment, 2. on-treatment on cycle 3 day 1, and 3. off-study. Additional exploratory imaging investigations, and assessment of circulating tumor cells are included for all patients. Trial therapy will last until withdrawal of consent, disease progression and/or unacceptable toxicity, whichever occurs first.
Investigators
Di Wu
chief
The First Hospital of Jilin University
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed Undifferentiated Pleomorphic Sarcoma with pathology review required for any outside samples.
- •Only patients with untreated and rejected first-line standard chemotherapy with high-grade Undifferentiated Pleomorphic Sarcoma can be enrolled
- •Any other histology or standard of care therapy not specifically addressed will be reviewed by the principal investigator and pathologist for final determination of eligibility.
- •Measurable disease as defined by RECIST v1.1
- •Radiographic progression as defined by RECIST v1.1, based on comparison between two radiographic studies no greater than 3 months apart. or Inability to undergo complete resection of the disease by surgery.
- •Adequate organ function as defined:
- •Hematological
- •Absolute neutrophil count (ANC) ≥1,000 / microliter (mcL)
- •Platelets ≥75,000 / mcL
- •Hemoglobin ≥8 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
Exclusion Criteria
- •Prior therapy with anlotinib. Patients who have received prior tyrosine kinase inhibitor (TKI) therapy including imatinib, sunitinib, pazopanib, or similar. Patients who have received immunotherapy including Programmed death 1 (PD-1)/Programmed death-ligand 1 (PD-L1) and CTLA-
- •Hypersensitivity to anlotinib, pembrolizumab or any of its excipients.
- •Patients may not be receiving any other investigational agents (within 4 weeks prior to Cycle 1, day 1).
- •If subject received palliative surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Additional known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
- •Patients with end-organ dysfunction as defined in inclusion criterion (i.e. #6 above).
- •Patients with bone-only lesions.
- •Patients with underlying immune deficiency, chronic infections including HIV, hepatitis, or tuberculosis (TB) or autoimmune disease.
- •Any major unhealed wound, ulcer, or fracture occurred in a patient who had undergone major surgery or trauma within 4 weeks and/or had any bleeding or bleeding episodes which the degree is bigger than CTCAE 3 grade within 4 weeks prior to enrollment.
- •Arteriovenous thrombosis events occurred within 6 months. Such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis and pulmonary embolism
Arms & Interventions
anlotinib + Toripalimab
Concurrent anlotinib and Toripalimab therapy, with Blood Draw and Tumor Specimen Collection for correlative studies
Intervention: Anlotinib
anlotinib + Toripalimab
Concurrent anlotinib and Toripalimab therapy, with Blood Draw and Tumor Specimen Collection for correlative studies
Intervention: Toripalimab
anlotinib + Toripalimab
Concurrent anlotinib and Toripalimab therapy, with Blood Draw and Tumor Specimen Collection for correlative studies
Intervention: Blood Draw
anlotinib + Toripalimab
Concurrent anlotinib and Toripalimab therapy, with Blood Draw and Tumor Specimen Collection for correlative studies
Intervention: Tumor Specimen Collection
Outcomes
Primary Outcomes
Rate of Participants Achieving 3-Month Progression-Free Survival (PFS)
Time Frame: 3 Months after start of protocol therapy
Rate of participants who are progression-free at 3 months after the start of protocol therapy, using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Progression-free survival (PFS) is defined as the time from treatment initiation until documented disease progression or death (by any cause, in the absence of progression).
Secondary Outcomes
- Rate of Participants Achieving Objective Response (ORR)(3, 6, and 12 Months after start of protocol therapy)
- Rate of Participants Achieving 6-Month and 12-Month Progression-Free Survival (PFS)(6 Months and 12 Months after start of protocol therapy)
- Rate of Participants Achieving Clinical Benefit (CBR)(3, 6, and 12 Months after the start of protocol therapy)
- Time to initial Response（TTR）(up to two year)
- Safety and Toxicity Profile: Rate of Toxicity in Study Participants(Up to 30 days after the end of protocol therapy)
- Duration of Response（DOR）(up to two year)
- Overall Survival (OS)(Through Study Completion, an Average of 12 months)