Study of Anlotinib Hydrochloride and Toripalimab in Subjects With Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma

NCT03946943 | Unknown Phase 2

• 1 other identifier: FHJLU-003
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Soft Tissue Sarcomas; Undifferentiated Pleomorphic Sarcoma

Keywords

TKI; PD-1 inhibitor; Anlotinib

Outcome Measures

Primary Outcomes (1)

• Rate of Participants Achieving 3-Month Progression-Free Survival (PFS)

  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).

  3 Months after start of protocol therapy

Secondary Outcomes (7)

• 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 Objective Response (ORR)

  3, 6, 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

• Duration of Response（DOR）

  up to two year

• Time to initial Response（TTR）

  up to two year

Other Outcomes (5)

• Change in quantity of CD3+ T-cells in Peripheral Blood and Tumor Tissue

  Baseline, cycle 3, and off-study, an Average of 12 months

• Expression Category of T-cell subsets in Tumor Tissue

  Baseline, cycle 3, and off-study, an Average of 12 months

• Absolute Change in T-cell Marker Levels in Peripheral Blood and Tumor Tissue

  Baseline, Cycle 3, Progression, an Average of 12 months

Study Arms (1)

anlotinib + Toripalimab

EXPERIMENTAL

Concurrent anlotinib and Toripalimab therapy, with Blood Draw and Tumor Specimen Collection for correlative studies

Drug: Anlotinib; Drug: Toripalimab; Procedure: Blood Draw; Procedure: Tumor Specimen Collection

Interventions

Anlotinib DRUG

Once a day dosing of anlotinib alone for the first 7 days, Anlotinib ( 12mg, QD, PO, d1-14, 21 days per cycle), take once when limosis in the morning. If patients cannot suffer from AEs, they can get declined dosage.

anlotinib + Toripalimab

Toripalimab DRUG

Toripalimab 240mg shall be administered via intravenous (IV) infusion, once every 21 days, on day 8 and day 29 of the first cycle, and days 1 and 22 of the following cycles.

anlotinib + Toripalimab

Blood Draw PROCEDURE

Peripheral blood draws for correlative studies characterizing T-cells in peripheral blood will be performed at three timepoints: 1) pre-treatment, 2) on-treatment on cycle 3 day 1, and 3) off-study.

Also known as: Phlebotomy

anlotinib + Toripalimab

Tumor Specimen Collection PROCEDURE

Tumor specimen collection via core needle biopsy for correlative studies characterizing T-cells in tumor tissue will occur at three timepoints: 1) pre-treatment, 2) on-treatment on cycle 3 day 1, and 3) off-study.

Also known as: Core-Needle Biopsy

anlotinib + Toripalimab

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Renal
• Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance ≥ 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN. (GFR can also be used in place of creatinine or CrCl). Creatinine clearance should be calculated per institutional standard.
• Hepatic
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN.
• Aspartate Aminotransferase (AST/SGOT) and Alanine Transaminase (ALT/SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases.

You may not qualify if:

• 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-4.
• 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 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
• History of steroid-related (non-infectious) pneumonia or current pneumonia.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Concomitant (or receipt of) treatment with medications that may affect the metabolism of pembrolizumab and/or axitinib within 7 days prior to Cycle 1, day 1 of anlotinib.
• Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Any uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia

Sponsors & Collaborators

• Di Wu: lead

Study Sites (1)

First Hospital of Jilin University

Changchun, Jilin, China

Location

Related Publications (1)

• Van Glabbeke M, Verweij J, Judson I, Nielsen OS; EORTC Soft Tissue and Bone Sarcoma Group. Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer. 2002 Mar;38(4):543-9. doi: 10.1016/s0959-8049(01)00398-7.

  PMID: 11872347 BACKGROUND

MeSH Terms

Conditions

Sarcoma; Histiocytoma, Malignant Fibrous

Interventions

anlotinib; toripalimab; Blood Specimen Collection; Phlebotomy; Biopsy, Needle

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Therapeutics; Biopsy; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Central Study Contacts

Di Wu

CONTACT

139 4488 8991; Wudi991202@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: chief

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 13, 2019
• Study Start: July 19, 2019
• Primary Completion: July 19, 2022
• Study Completion: July 19, 2023
• Last Updated: July 10, 2019

Record last verified: 2019-07

Locations

CN (1)