Advanced Soft-tissue Sarcoma
Conditions
Brief summary
A Phase I dose-finding stage for the LB-100 plus doxorubicin combination is planned for an initial set of 9-18 patients (21-day cycles). After that, in the Phase II part, patients will be randomized (ratio 1:1) to either the experimental arm (LB-100 plus doxorubicin combination) or the control arm (doxorubicin alone) to, comparatively, evaluate the efficacy of the LB-100 plus doxorubicin combination vs. doxorubicin alone
Interventions
DRUGLB-100 plus Doxorrubicin
In Phase one the intervention will be LB-100 plus Doxorrubicin. The experimental arm in Phase II will also be LB-100 plus Doxorrubicin
DRUGDoxorubicin
The control arm in Phase II will be Doxorrubicin alone
Sponsors
Grupo Espanol de Investigacion en Sarcomas
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A Phase I dose-finding stage for the LB-100 plus doxorubicin combination is planned for an initial set of 9-18 patients (21-day cycles) In the Phase II part, patients will be enrolled in the trial via randomization. A randomization module (integrated in the eCRF system) will be used to assign patients to either the experimental arm (LB-100 plus doxorubicin) or to the control arm (doxorubicin alone) (1:1 ratio)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase I: 1. The patient must provide written informed consent prior to performance of study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol. 2. Age ≥ 18 years. 3. Diagnosis of advanced/metastatic soft tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, myxoid and hypercellular myxoid liposarcoma, myxofibrosarcoma, NOS sarcoma, synovial sarcoma, fibrosarcoma, or malignant nerve sheath tumor) confirmed by central pathology review. 4. Mandatory pre-treatment formalin-fixed paraffin embedded (FFPE) tumor tissue must be provided for all subjects without exception for central pathology review and the translational study. If archive biopsy is not available or is older than 3 months, the patient must be willing to have a pre-treatment re-biopsy of primary or metastatic tumor (baseline biopsy) within 28 days prior to enrollment. 5. The patient must be willing to undergo a second mandatory biopsy just before the initiation of the 3rd cycle and agree that this sample is used for the translational study. 6. Measurable disease according to RECIST v1.1 criteria. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 8. The patient must be naïve of any previous treatment with anthracyclines (not even in adjuvant chemotherapy). 9. Adequate organ, hepatic, renal, cardiac, and hematologic function. 10. Laboratory tests as follows: * Absolute neutrophil count ≥ 1,200/mm³ * Platelet count ≥ 100,000/mm³ * Hg \> 9 g/dL * Bilirubin ≤ 1.5 mg/dL * PT and INR ≤ 1.5 * AST and ALT ≤ 2.5 times ULN * Creatinine ≤ 1.5 mg/dL or estimated creatinine clearance ≥ 60 mL/min * Blood glucose \< 150 mg/dL 11. Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan assessed within 28 days before enrollment. 12. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment. Patients must not be pregnant or nursing at study entry. 13. Women and men of reproductive potential must have agreed to use an effective contraceptive method during study treatment and for 3 months after the last dose of study drug.
Exclusion criteria
Phase I: 1. Diagnosis different from the elegible histological subtypes. 2. Previous treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or any other systemic therapy. The exception is previous systemic therapy for a previous neoplasm (see
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximun Tolerated Dose (MTD) (Phase I) | After six months | The MTD of LB-100 in combination with doxorubicin will be determined by assessing adverse events according to CTCAE v5.0. |
| Progression-free survival (PFS) (Phase II) | After two years | Efficacy measured by median PFS according to RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) (Phase I) | After six months | Efficacy measured by median PFS according to RECIST v1.1 |
| Adverse Events (Phase I and II) | Between six months and two years | Safety profile/Toxicity assessed by adverse events related to study drugs |
| EORTC QLQ-C30 questionnaire (Phase I and II) | Between six months and two years | Quality of life assessed by using the EORTC QLQ-C30 questionnaire. |
| Overall survival (OS) (Phase I and II) | Between six months and two years | Censored on the last date a subject was known to be alive |
| Overall Response Rate (ORR) (Phase I and II) | Between six months and two years | Efficacy measured by the ORR, which is defined as the number of subjects with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) divided by the number of response evaluable subjects. |
Countries
Spain
Outcome results
None listed