Phase I/II randomized trial of LB-100 plus doxorubicin vs. doxorubicin alone in first line of advanced soft tissue sarcomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Asoc Grupo Espanol De Investigacion En Sarcomas

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 May 2024 → 13 Nov 2025

Decision date (initial)

2024-05-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-510877-67-00

EudraCT number

2019-003034-16

ClinicalTrials.gov

NCT05809830

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

PHASE I
Primary clinical objective
• To determine the maximum tolerated dose (MTD) of LB-100 in combination with doxorubicin, to be used as recommended phase 2 dose (RP2D).
PHASE II
Primary clinical objective
• To comparatively evaluate the efficacy of the LB-100 plus doxorubicin combination vs. doxorubicin alone as measured by median progression-free survival (PFS).

Secondary objectives 9

1. Phase I: To evaluate the safety profile.
2. Phase I: To evaluate the overall response rate (ORR)
3. Phase I: To evaluate progression-free survival (PFS)
4. Phase I: To evaluate overall survival (OS)
5. Phase I: To evaluate quality of life
6. Phase II: To evaluate the overall response rate (ORR)
7. Phase II: To evaluate overall survival (OS)
8. Phase II: To evaluate the safety profile
9. Phase II: To evaluate quality of life

Conditions and MedDRA coding

Phase I:Adult patients with centrally confirmed diagnosis of advanced/metastatic undifferentiated pleomorphic sarcoma, leiomyosarcoma, myxoid/and hypercellular myxoid liposarcoma, myxofibrosarcoma, NOS sarcoma, synovial sarcoma, fibrosarcoma, malignant peripheral nerve sheath tumor, epitheloid sarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma and angiosarcoma, high-grade uterine sarcomas (excluding those with BCOR or NTRK translocation). Phase II:Adult patients with centrally confirmed diagnosis of advanced/metastatic undifferentiated pleomorphic sarcoma or leiomyosarcoma.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 24

1. Phase I: 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. Phase I: Age ≥ 18 years.
3. Phase I: Diagnosis of advanced/metastatic soft tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, myxoid and hypercellular myxoid liposarcoma, myxofibrosarcoma, NOS sarcoma, synovial sarcoma, fibrosarcoma, malignant peripheral nerve sheath tumor, epitheloid sarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma, angiosarcoma and high-grade uterine sarcomas (excluding those with BCOR or NTRK translocation)) confirmed by central pathology review.
4. Phase I: 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. Phase I: Measurable disease according to RECIST v1.1 criteria.
6. Phase I: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
7. Phase I: The patient must be naïve of any previous treatment with anthracyclines (not even in adjuvant chemotherapy).
8. Phase I: Adequate organ, hepatic, renal, cardiac, and hematologic function.
9. Phase I: 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. Phase I: Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan assessed within 28 days before enrollment.
11. Phase I: 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. Phase I: 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.
13. Phase II: 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.
14. Phase II: Age ≥ 18 years.
15. Phase II: Diagnosis of advanced/metastatic soft tissue sarcoma (undifferentiated pleomorphic sarcoma or leiomyosarcoma) confirmed by central pathology review.
16. Phase II: 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.
17. Phase II: Measurable disease according to RECIST v1.1 criteria.
18. Phase II: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
19. Phase II: The patient must be naïve of any previous treatment with anthracyclines (not even in adjuvant chemotherapy).
20. Phase II: Adequate organ, hepatic, renal, cardiac, and hematologic function.
21. Phase II: 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
22. Phase II: Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan assessed within 28 days before enrollment.
23. Phase II: 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.
24. Phase II: 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 24

1. Phase I: Diagnosis different from the elegible histological subtypes.
2. Phase I: 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. Phase I: 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. Phase I: 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. Phase I: 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. Phase I: Evidence of a bleeding diathesis.
7. Phase I: Ongoing cardiac dysrhythmias > Grade 2.
8. Phase I: Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.
9. Phase I: History of allergy to study drug components.
10. Phase I: 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. Phase I: Presence of brain or central nervous system metastases at the time of enrollment.
12. Phase I: Patient is unwilling to provide mandatory translational tumor samples or biopsies (if required) cannot be easily taken.
13. Phase II: Diagnosis of any sarcoma different from undifferentiated pleomorphic sarcoma and leiomyosarcoma.
14. Phase II: 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.
15. Phase II: 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).
16. Phase II: 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).
17. Phase II: 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
18. Phase II: Evidence of a bleeding diathesis.
19. Phase II: Ongoing cardiac dysrhythmias > Grade 2.
20. Phase II: Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.
21. Phase II: History of allergy to study drug components.
22. Phase II: 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.
23. Phase II: Presence of brain or central nervous system metastases at the time of enrollment.
24. Phase II: Patient is unwilling to provide mandatory translational tumor samples or biopsies (if required) cannot be easily taken.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I: The MTD of LB-100 in combination with doxorubicin will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol.
2. Phase II: Progression-free survival (PFS) (according to central radiology review): Efficacy measured by median PFS according to RECIST v1.1. PFS for each patient is defined as the time in months from date of randomization to date of progression or to death due to any cause, whatever occurs first.

Secondary endpoints 9

1. Phase I: Safety profile: Toxicity assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.
2. Phase I: Overall Response Rate (ORR) (according to central radiology review): 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 (according to RECIST v1.1 and Choi). Choi evaluation is an exploratory task for central radiology review only.
3. Phase I: Progression-free survival (PFS) (according to central radiology review): Efficacy measured by median PFS according to RECIST v1.1. PFS for each patient is defined as the time in months from date of enrollment to date of progression or death due to any cause, whatever occurs first.
4. Phase I: Overall survival (OS): Efficacy measured by OS, which is defined as the time in months from date of enrollment to date of death due to any cause. OS will be censored on the last date a subject was known to be alive.
5. Phase I: Quality of life: Assessed by using the EORTC QLQ-C30 questionnaire.
6. Phase II: Overall Response Rate (ORR) (according to central radiology review): 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 (according to RECIST v1.1 and Choi). Choi evaluation is an exploratory task for central radiology review only.
7. Phase II: Overall survival (OS): Efficacy measured by OS, which is defined as the time in months from date of randomization to date of death due to any cause. OS will be censored on the last date a subject was known to be alive.
8. Phase II: Safety profile: Toxicity assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.
9. Phase II: Quality of life: Assessed by using the EORTC QLQ-C30 questionnaire.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Asoc Grupo Espanol De Investigacion En Sarcomas

Sponsor organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Address

Calle Del Conde De Aranda 20 Planta 5 Puerta Derecha

City

Madrid

Postcode

28001

Country

Spain

Scientific contact point

Organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Contact name

Adriana Rojo

Public contact point

Organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Contact name

Adriana Rojo

Third parties 1

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications