Trial Title:
Phase I/II of LB-100 Plus Doxorubicin vs. Doxorubicin Alone in First Line of Advanced Soft Tissue Sarcomas
NCT ID:
NCT05809830
Condition:
Advanced Soft-tissue Sarcoma
Conditions: Official terms:
Sarcoma
Doxorubicin
LB100
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
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)
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LB-100 plus Doxorrubicin
Description:
In Phase one the intervention will be LB-100 plus Doxorrubicin. The experimental arm in
Phase II will also be LB-100 plus Doxorrubicin
Arm group label:
LB-100 plus doxorubicin
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
The control arm in Phase II will be Doxorrubicin alone
Arm group label:
Doxorubicin alone
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
Criteria for eligibility:
Criteria:
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 exclusion criteria 10), if this is controlled,
as long as it did not include anthracyclines.
3. 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).
4. HBV and HCV serologies must be performed prior to inclusion. If HbsAg is positive it
is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+). If
these were positives the inclusion is not recommended, remaining at investigators'
discretion the preventive treatment with lamivudine. If a potential patient is
positive for anti-HCV antibodies, presence of the virus should be ruled out with a
qualitative PCR, or the patient should NOT be included in the study (if a
qualitative PCR cannot be performed then patient will not be able to enter the
study).
5. 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
6. Evidence of a bleeding diathesis.
7. Ongoing cardiac dysrhythmias > Grade 2.
8. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for
females) on baseline ECG.
9. History of allergy to study drug components.
10. 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.
11. Presence of brain or central nervous system metastases at the time of enrollment.
12. Patient is unwilling to provide mandatory translational tumor samples or biopsies
(if required) cannot be easily taken.
Inclusion Criteria Phase II:
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 obtainedprior 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 or leiomyosarcoma) 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. Measurable disease according to RECIST v1.1 criteria.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
7. The patient must be naïve of any previous treatment with anthracyclines (not even in
adjuvant chemotherapy).
8. Adequate organ, hepatic, renal, cardiac, and hematologic function.
9. 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 10. Left ventricular ejection fraction ≥ 50% by
echocardiogram or MUGA scan assessed within 28 days before enrollment.
11. 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.
12. 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 II:
1. Diagnosis of any sarcoma different from undifferentiated pleomorphic sarcoma and
leiomyosarcoma.
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 exclusion criteria 10), if this is controlled,
as long as it did not include anthracyclines.
3. 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).
4. HBV and HCV serologies must be performed prior to inclusion. If HbsAg is positive it
is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+). If
these were positives the inclusion is not recommended, remaining at investigators'
discretion the preventive treatment with lamivudine. If a potential patient is
positive for anti-HCV antibodies, presence of the virus should be ruled out with a
qualitative PCR, or the patient should NOT be included in the study (if a
qualitative PCR cannot be performed then patient will not be able to enter the
study).
5. 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
6. Evidence of a bleeding diathesis.
7. Ongoing cardiac dysrhythmias > Grade 2.
8. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for
females) on baseline ECG.
9. History of allergy to study drug components.
10. 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.
11. Presence of brain or central nervous system metastases at the time of enrollment.
12. Patient is unwilling to provide mandatory translational tumor samples or biopsies
(if required) cannot be easily taken.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital de la Santa Creu i Sant Pau
Address:
City:
Barcelona
Zip:
08026
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Raúl Terés Lleida
Investigator:
Last name:
Raúl Terés Lleida
Email:
Principal Investigator
Investigator:
Last name:
Ana Serbio
Email:
Sub-Investigator
Investigator:
Last name:
Antonio López Pousa
Email:
Sub-Investigator
Facility:
Name:
Hospital Clínico Universitario de Valencia
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Status:
Recruiting
Contact:
Last name:
José Alejandro Perez Fidalgo
Investigator:
Last name:
José Alejandro Pérez Fidalgo
Email:
Principal Investigator
Investigator:
Last name:
Gema Bruixola Campos
Email:
Sub-Investigator
Investigator:
Last name:
Valentina Gambardella
Email:
Sub-Investigator
Investigator:
Last name:
Desamparados Roda Pérez
Email:
Sub-Investigator
Investigator:
Last name:
Marisol Huerta Álvaro
Email:
Sub-Investigator
Investigator:
Last name:
Susana Rosselló Keränen
Email:
Sub-Investigator
Facility:
Name:
Hospital Clínico San Carlos
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Aránzazu Manzano Fernández
Investigator:
Last name:
Aránzazu Manzano Fernández
Email:
Principal Investigator
Investigator:
Last name:
Antonio Casado
Email:
Sub-Investigator
Investigator:
Last name:
Gloria Marquina
Email:
Sub-Investigator
Facility:
Name:
Hospital Fundación Jiménez Díaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Javier Martín Broto
Investigator:
Last name:
Javier Martín Broto
Email:
Principal Investigator
Investigator:
Last name:
Nadia Hindi Muñiz
Email:
Sub-Investigator
Facility:
Name:
Hospital Universitario La Paz
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Hospital Clínico Universitario Virgen de la Arrixaca
Address:
City:
Murcia
Zip:
30120
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Jerónimo Martínez García
Investigator:
Last name:
Jerónimo Martínez García
Email:
Principal Investigator
Investigator:
Last name:
José Luís Alonso Romero
Email:
Sub-Investigator
Investigator:
Last name:
Pilar Sánchez Henarejos
Email:
Sub-Investigator
Investigator:
Last name:
Ana Puertes Boix
Email:
Sub-Investigator
Investigator:
Last name:
María Dolores Jiménez Lucas
Email:
Sub-Investigator
Investigator:
Last name:
Beatriz Álvarez Abril
Email:
Sub-Investigator
Start date:
May 29, 2023
Completion date:
May 8, 2026
Lead sponsor:
Agency:
Grupo Espanol de Investigacion en Sarcomas
Agency class:
Other
Source:
Grupo Espanol de Investigacion en Sarcomas
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05809830
