Soft Tissue Sarcoma
Conditions
Keywords
Soft Tissue Sarcoma, Arginine, Arginine Deiminase, ADI-PEG 20, Pegargiminase, Leiomyosarcoma
Brief summary
To compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.
Detailed description
This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial that will compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.
Interventions
DRUGADI PEG20
Treatment for advanced or metastatic uterine/non-uterine leiomyosarcoma (LMS)
OTHERPlacebo
Treatment for advanced or metastatic uterine/non-uterine leiomyosarcoma (LMS)
Sponsors
Polaris Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial
Intervention model description
This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial that will compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* A subject will be eligible for study participation if he/she meets the following criteria: 1. Histologically or cytologically confirmed, grade 2 or 3, LMS STS that would be standardly treated with Gem or GemDoc. 2. Determination of LMS subtype: uterine or non-uterine. 3. Measurable disease per RECIST 1.1 (Appendix A), defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam. 4. Previous treatment with up to 2 systemic regimens, including at least 1 systemic regimen containing doxorubicin. 5. Treatment \> one year ago in the adjuvant/neoadjuvant setting with Gem or Doc is allowed. 6. Age \>18 years. 7. Eastern Cooperative Oncology Group (ECOG) performance status of \< 1 at enrollment (Appendix B). 8. Leukocytes ≥ 3,000/mcL. 9. Absolute neutrophil count ≥ 1,500/mcL. 10. Platelets ≥ 100,000/mcL. 11. Hemoglobin ≥ 8.0 g/dL 12. Total bilirubin ≤ 2 x ULN. (≤ 3 x ULN for potential subjects with Gilbert's Disease) 13. AST(SGOT)/ALT(SGPT) ≤ 3 x ULN (or ≤ 5 x ULN if liver metastases are present) 14. Creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault equation). 15. Serum uric acid ≤ 8 mg/dL (with or without medication control). 16. QTc interval range from 350 to 450 ms for adult men and from 360 to 460 ms for adult women. 17. Subjects and their partners must be asked to use appropriate contraception. They must agree to use 2 forms of contraception or agree to refrain from intercourse for the duration of the study and for 35 days after the last dose of ADI-PEG 20 or for at least 3 months (male subjects) or 6 months (female subjects) after treatment with gemcitabine, whichever is the longer duration. 18. Ability to understand and willingness to sign the informed consent form. 19. No concurrent investigational drug studies are allowed.
Exclusion criteria
* A subject will not be eligible for study participation if he/she meets any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary End Point of PFS | Subjects will receive triplet combination treatment followed by weekly monotherapy ADI-PEG 20 or PBO (Each cycle is 21 days). Subjects tolerating chemotherapy may continue chemotherapy beyond 8 cycles and up to 104 weeks (~2 years). | The primary objective is to compare the primary endpoint of PFS in subjects treated with the arginine degrading enzyme ADI-PEG 20 plus Gem and Doc (ADIGemDoc) or PBO plus Gem and Doc (PBOGemDoc) in the 2nd or 3rd line setting using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by blinded independent central review committee (BICR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary End Point of ORR (CR+PR) | Subjects will receive triplet combination treatment followed by weekly monotherapy ADI-PEG 20 or PBO (Each cycle is 21 days). Subjects tolerating chemotherapy may continue chemotherapy beyond 8 cycles and up to 104 weeks (~2 years). | The secondary objectives are to compare ADIGemDoc versus PBOGemDoc with respect to: Objective response rate (ORR) (complete response \[CR\] + partial response \[PR\]) The secondary endpoint of ORR will be assessed by BICR using RECIST 1.1 and tested using a CMH test stratified by the stratification factors used during the randomization based on the ITT population. |
| Secondary End Point of Overall Survival (OS) | Subjects will receive triplet combination treatment followed by weekly monotherapy ADI-PEG 20 or PBO (Each cycle is 21 days). Subjects tolerating chemotherapy may continue chemotherapy beyond 8 cycles and up to 104 weeks (~2 years). | The secondary objectives are to compare ADIGemDoc versus PBOGemDoc with respect to: OS The secondary endpoint of OS will be tested using a log-rank test stratified by the stratification factors used during the randomization based on the ITT population. A stratified Cox model will be used to estimate HR and 95% CI, and KM curves will be used to estimate OS median and 95% CI. |
| Secondary End Point of Safety and Tolerability | Subjects will receive triplet combination treatment followed by weekly monotherapy ADI-PEG 20 or PBO (Each cycle is 21 days). Subjects tolerating chemotherapy may continue chemotherapy beyond 8 cycles and up to 104 weeks (~2 years). | All clinically significant abnormalities and deteriorations will be followed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE V5). |
Countries
Canada, Taiwan, United States
Contacts
STUDY_DIRECTORJohn S Bomalaski
Polaris Group
Outcome results
None listed