Clinical trial NCT06981637: Pegylated Liposomal Doxorubicin (PLD) Versus Active Surveillance for Advanced Soft Tissue Sarcoma Patients Who Had Controlled Disease After Standard Anthracycline-based Treatment (MELODY)
Official title: Maintenance Pegylated Liposomal Doxorubicin (PLD) Versus Active Surveillance for Advanced Soft Tissue Sarcoma Patients Who Had Controlled Disease After Standard Anthracycline-based Treatment (MELODY)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Advanced Soft Tissue Sarcoma
Keywords: advanced soft tissue sarcoma
pegylated liposomal doxorubicin
open label randomized
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital
name: Chang Gung Memorial Hospital
name: Kaohsiung Medical University Chung-Ho Memorial Hospital
name: Taipei Veterans General Hospital, Taiwan
name: National Cheng-Kung University Hospital
name: Tri-Service General Hospital
name: China Medical University Hospital
First posted: 2025-05-21
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An investigator-initiated,A multinational open label randomized (2:1 experimental vs control) phase II study.

Stratified randomization factor：

1. The response after first-line anthracycline-based treatment (CR/PR vs SD)
2. The study country.

Patients will be randomized 2:1 using the method of minimization accounting for the stratification factors above.
Primary purpose: TREATMENT

Brief summary: Maintenance Pegylated Liposomal Doxorubicin (PLD) Versus Active Surveillance for Advanced Soft Tissue Sarcoma Patients Who Had Controlled Disease After Standard Anthracycline-based Treatment (MELODY)

Detailed description: Patients enrolled will be randomized to either experimental arm or control arm. Patients in experimental arm will receive pegylated liposomal doxorubicin (PLD) 40mg/m2 every 4 weeks. Maintenance PLD could be administered up to a total of 12 cycles. Patients in control arm will receive active surveillance without treatment (treatment holiday).

Eligibility criteria: Inclusion Criteria:

1. A histologically confirmed advanced soft tissue sarcoma. Note that subtypes typically do not use chemotherapy as standard treatment are not allowed, such as alveolar soft part sarcoma, solitary fibrous tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma)
2. Patients received first-line anthracycline-based treatment for a minimum of 4 cycles and a maximum of 8 cycles.
3. The best response after first-line anthracycline-based treatment must be either a complete response, partial response, or stable disease as defined by RECIST 1.1.

   The best response should be attributed solely to systemic treatment and not to local therapy. All the patients must have at least one measurable tumor based on RECIST 1.1 before initiating first-line anthracycline-based treatment.
4. Patients must be randomized within 8 weeks of their last dose of anthracycline-based treatment
5. Patients have a life expectancy ≥ 3 months
6. Patients older than 18 years old.
7. ECOG performance status of 0 to 1.
8. Patients must have adequate organ function and marrow reserve measured within 7 days prior to randomization as defined below:

   1. Hemoglobin ≥ 9.0 g/dL;
   2. Absolute neutrophil count ≥ 1,500/mm3;
   3. Platelets ≥ 100,000/mm3;
   4. Total bilirubin ≤ 1.5 x upper normal limit;
   5. AST(SGOT)/ALT(SGPT) ≤ 2.5 x upper normal limit; for patients with liver metastases AST(SGOT)/ALT(SGPT) ≤ 5 x upper normal limit is allowed;
   6. Serum creatinine ≤ 1.5mg/dL or creatinine clearance ≥50ml/min;
   7. All women of childbearing potential must have a negative pregnancy test obtained within 72 hours before starting therapy.
9. For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
10. Patients with reproductive potential must use effective contraception (hormone orbarrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after the completion of therapy.
11. Patients must be able to comply with study procedures and sign informed consent.

Exclusion Criteria:

1. Known allergy history to PLD or other drugs of liposome-based formulation.
2. LVEF \< 50% at screening as determined by UCG or MUGA.
3. Serious non-healing wound, ulcer, or bone fracture not related to underlying sarcoma.
4. Major surgical procedure, open biopsy, significant traumatic injury, or radiotherapy within 21 days prior to randomization.
5. Severe, uncontrolled medical conditions including severe liver disease, heart disease, uncontrolled diabetes or hypertension, or pulmonary disease.
6. Psychiatric illness or social situation that would preclude study compliance.
7. Women with pregnant or breast feeding (a urine pregnancy test must be performed on all female patients who are of childbearing potential before entering the study, and the result must be negative.
8. Another previous malignancy diagnosed within the past 3 years. Patients with carcinoma in situ and stage I malignancy under active surveillance (no medical treatment needed) are allowed for enrollment.
9. Active CNS metastasis defined by clinical symptoms, cerebral edema, steroid or anti- convulsant requirement, or progressive growth. Patients with a history of CNS metastasis or cord compression are allowed in the study if they have been treated and are clinically stable.
10. Patients with active hepatitis B. However, patients with controlled hepatitis B under anti-viral agent are allowed.

Primary outcomes:
measure: Progression-free survival from randomization
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 2 years
measure: Time to next treatment (TTNT)
timeFrame: Up to approximately 2 years
measure: Objective response rate (ORR)
timeFrame: Up to approximately 2 years
measure: Frequency and severity of AE
timeFrame: Up to approximately 2 years
measure: Safety of interest: cardiac function as assessed by LVEF
timeFrame: Up to approximately 2 years
measure: Quality of Life Effects on patient-reported outcomes as assessed by EORTC QLQ C30
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital,
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
affiliation: Taiwan Cooperative Oncology Group, National Health Research Institutes
name: Tsang-Wu Liu, MD
role: STUDY_DIRECTOR
affiliation: National Taiwan University Hospital
name: Tom Wei-Wu Chen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: