Sarcoma
Conditions
Keywords
marine derived alkaloid, PD1 inhibitor, CTLA4 inhibitor
Brief summary
This is a Phase 2 study using talimogene laherparepvec, nivolumab, and trabectedin as first, second or third line therapy for advanced sarcoma, including desmoid tumor and chordoma.
Detailed description
This is a Phase 2 study using talimogene laherparepvec, nivolumab, and trabectedin as first, second or third line therapy for advanced sarcoma, including desmoid tumor and chordoma. The primary objective is to determine progression-free survival (PFS) at month 12. The secondary objectives are (1) To evaluate the best overall response (BOR) and duration of response (DOR) by RECIST v1.1 via CT scan or MRI at 6,12,18, and 24 weeks post treatment, (2) To determine progression-free survival rate (PFS) at 6 and 9 months, (3) To determine overall survival rate at 6, 9, and 12 months, (4) To determine the incidence of conversion of an unresectable tumor to a resectable tumor, and (5) To evaluate the incidence of adverse events related to TALIMOGENE LAHERPAREPVEC in combination with nivolumab and trabectedin. The exploraratory objective is to correlate response with immune cell trafficking in the tumor microenvironment (TME) of resected tumors. The primary endpoint is Progression free survival at month 12. The secondary endpoints are: 1) Best overall response (BOR) and duration of response (DOR) by RECIST v1.1 via CT scan or MRI at 6,12,18 and 24 weeks post treatment, 2) PFS rate at 6 and 9 months • Overall survival rate at 6, 9, and 12 months, 3) Incidence of conversion of an unresectable tumor to a resectable tumor, 4) Incidence of adverse events related to TALIMOGENE LAHERPAREPVEC in combination with nivolumab and trabectedin. The exploratory endpoint is correlation of response with immune cell trafficking in the tumor microenvironment of resected tumors. Forty male and female subjects \> 18 years of age, of any ethnicity, with advanced sarcoma, including desmoid tumor and chordoma will be treated.
Interventions
DRUGTalimogene Laherparepvec 100000000 PFU/1 ML Injection Suspension [IMLYGIC]
Talimogene laherparepvec, 1Bil is given intratumorally every 2 weeks according to tumor size
DRUGNivolumab IV Soln 100 MG/10ML
NIVOLUMAB 240 mg IV over 30 min q 2 weeks
DRUGTrabectedin 0.25 MG/1 VIAL Intravenous Powder for Solution
TRABECTEDIN 1.2 mg/m2 CIV over 24 hours q3 weeks
Sponsors
Sarcoma Oncology Research Center, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Forty male and female patients with advanced sarcoma including desmoid tumor and chordoma will be treated with talimogene laherparepvec, nivolumab and trabectedin will be studied and evaluated for progression free survival at month 12.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Individuals must meet all of the inclusion criteria in order to be eligible to participate in the study, as follows: * Male or Female ≥ 18 years of age * Pathologically confirmed diagnosis of locally advanced unresectable or metastatic sarcoma including desmoid tumor and chordoma * Ability to understand the purposes and risks of the study and has signed and dated a written informed consent form approved by the Investigator's IRB/Ethics Committee * Willingness to comply with all study procedures and availability for the duration of the study. * Previously untreated or treated patient with measurable disease by RECIST v1.1, and at least, one accessible tumor for intratumoral injection of TALIMOGENE LAHERPAREPVEC * ECOG performance status ≤ 1 * Life expectancy of at least 3 months * Acceptable liver function: Bilirubin \<1.5 times upper limit of normal (ULN; except subjects with Gilbert Syndrome who must have a total bilirubin level \< 3.0 ULN); AST (SGOT), ALT (SGPT) and alk phos \< 2.5 x ULN (\< 5 x ULN if liver metastases present) * Acceptable renal function: Creatinine \< 1.5 times ULN * Acceptable hematologic status: ANC \>1500 cells/μL or greater; Platelet count \>100,000/μL or greater; Hemoglobin \> 9.0 g/dL or greater * INR and PT \< 1.5 ULN unless taking anti-coagulation, in which case PT, INR and aPTT must be within therapeutic range of intended use of anticoagulants * All women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours of enrollment. If urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; all subjects must agree to use highly effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 5 months for women and 7 months for men after the last dose.
Exclusion criteria
* All individuals meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | 12 months | Progression free survival at month 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best overall response and duration of response | 12 months | • Best overall response (BOR) and duration of response (DOR) by RECIST v1.1 via CT scan or MRI at 6,12,18 and 24 weeks post treatment |
| Progression free survival rate | Nine months | Prgoression Free Survival rate at 6 and 9 months |
| )verall survival rate | 12 months | Overall survival rate at 6, 9, and 12 months |
| Convesion to resectable tumor | 12 months | Incidence of conversion of an unresectable tumor to a resectable tumor |
| Incidence of adverse events | 12 months | • Incidence of adverse events related to TALIMOGENE LAHERPAREPVEC in combination with nivolumab and trabectedin |
Countries
United States
Outcome results
None listed