Phase I/II of LB-100 Plus Doxorubicin vs. Doxorubicin Alone in First Line of Advanced Soft Tissue Sarcomas

NCT05809830 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: GEIS-74
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 6

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

Conditions

Advanced Soft-tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• Maximun Tolerated Dose (MTD) (Phase I)

  The MTD of LB-100 in combination with doxorubicin will be determined by assessing adverse events according to CTCAE v5.0.

  After six months

• Progression-free survival (PFS) (Phase II)

  Efficacy measured by median PFS according to RECIST v1.1

  After two years

Secondary Outcomes (5)

• Adverse Events (Phase I and II)

  Between six months and two years

• Overall Response Rate (ORR) (Phase I and II)

  Between six months and two years

• Progression-free survival (PFS) (Phase I)

  After six months

• Overall survival (OS) (Phase I and II)

  Between six months and two years

• EORTC QLQ-C30 questionnaire (Phase I and II)

  Between six months and two years

Study Arms (2)

LB-100 plus doxorubicin

EXPERIMENTAL

* LB-100 will be administered during the first 3 days of each cycle (days 1, 2, and 3) at RP2D as a 2-hour intravenous infusion (with 500 mL of physiological saline solution), every 3 weeks (21-day cycles until progression or intolerance). * Doxorubicin will be administered only once (day 1) of each cycle at RP2D as a 20-minute infusion after completion of LB-100, every 3 weeks (up to a maximum of 6 x 21-day cycles).

Drug: LB-100 plus Doxorrubicin

Doxorubicin alone

ACTIVE COMPARATOR

Control: Doxorubicin will be administered only once (day 1) of each cycle at RP2D as a 20-minute infusion every 3 weeks (up to a maximum of 6 x 21-day cycles).

Drug: Doxorubicin

Interventions

LB-100 plus Doxorrubicin DRUG

In Phase one the intervention will be LB-100 plus Doxorrubicin. The experimental arm in Phase II will also be LB-100 plus Doxorrubicin

LB-100 plus doxorubicin

Doxorubicin DRUG

The control arm in Phase II will be Doxorrubicin alone

Doxorubicin alone

Eligibility Criteria

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

You may qualify if:

• 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.
• Age ≥ 18 years.
• 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.
• 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.
• 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.
• Measurable disease according to RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• The patient must be naïve of any previous treatment with anthracyclines (not even in adjuvant chemotherapy).
• Adequate organ, hepatic, renal, cardiac, and hematologic function.
• 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

You may not qualify if:

• Diagnosis different from the elegible histological subtypes.
• Uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE version 5.0 Grade \>= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (\>= Grade 3).
• Any of the following diseases/illnesses within the previous 6 months:
• Myocardial infarction
• Severe or unstable angina
• Coronary or peripheral artery bypass graft
• Cerebrovascular accident or transient ischemic attack (TIA)
• Pulmonary embolism
• Evidence of a bleeding diathesis.
• Ongoing cardiac dysrhythmias \> Grade 2.
• Prolonged QTc interval (i.e., QTc \> 450 msec for males or QTc \> 470 msec for females) on baseline ECG.
• History of allergy to study drug components.
• History of another cancer with the exception of adequately treated basal cell carcinoma or in situ cervical cancer, or with a relapse-free interval longer than 3 years after treatment of the primary cancer with no substantial risk of recurrence.
• Presence of brain or central nervous system metastases at the time of enrollment.
• Patient is unwilling to provide mandatory translational tumor samples or biopsies (if required) cannot be easily taken.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (6)

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08026, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

Location

Hospital Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Murcia, 30120, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Valencia, 46010, Spain

Location

MeSH Terms

Interventions

LB100; Doxorubicin

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Javier Martín Broto

  Hospital Universitario Fundación Jiménez Díaz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: March 27, 2023
• First Posted: April 12, 2023
• Study Start: May 29, 2023
• Primary Completion: June 20, 2025
• Study Completion (Estimated): May 8, 2026
• Last Updated: March 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6)