Trial Outcomes & Findings for Efficacy and Safety of Plitidepsin in Patients With Advanced Unresectable or Metastatic, Relapsed/Refractory, Dedifferentiated Liposarcoma (DLPS): an Exploratory Phase II Multicenter Trial (NCT NCT01876043)
NCT ID: NCT01876043
Last Updated: 2021-01-25
Results Overview
Progression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
TERMINATED
PHASE2
24 participants
3 months
2021-01-25
Participant Flow
Participant milestones
| Measure |
Plitidepsin
Patients received Aplidin® as an i.v. 3-h infusion of 5 mg/m2/day on days 1 and 15 every 4 weeks (q4wk).Patients discontinued Aplidin if one of the following occurred: consent withdrawal, unacceptable toxicity, disease progression (RECIST v1.1), intercurrent illness or investigator's decision.
Single-arm phase II clinical trial based on a two-stage optimal Simon's design with 37 evaluable patients (first stage: 17 patients) used to distinguish a favorable true non-progression rate of 40% from a null rate of 20% (90% power and 10% type I error).
* Stage 1(17 participants): if \<=3 non-progressions at 3 months, the study was stopped early. Otherwise, the second group of 20 participants was recruited.
* Stage 2 (37 participants): if \>= 11 non-progressions, Aplidin was considered promising.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
Interim Analysis Population
|
17
|
|
Overall Study
COMPLETED
|
22
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Plitidepsin
Patients received Aplidin® as an i.v. 3-h infusion of 5 mg/m2/day on days 1 and 15 every 4 weeks (q4wk).Patients discontinued Aplidin if one of the following occurred: consent withdrawal, unacceptable toxicity, disease progression (RECIST v1.1), intercurrent illness or investigator's decision.
Single-arm phase II clinical trial based on a two-stage optimal Simon's design with 37 evaluable patients (first stage: 17 patients) used to distinguish a favorable true non-progression rate of 40% from a null rate of 20% (90% power and 10% type I error).
* Stage 1(17 participants): if \<=3 non-progressions at 3 months, the study was stopped early. Otherwise, the second group of 20 participants was recruited.
* Stage 2 (37 participants): if \>= 11 non-progressions, Aplidin was considered promising.
|
|---|---|
|
Overall Study
Death
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Efficacy and Safety of Plitidepsin in Patients With Advanced Unresectable or Metastatic, Relapsed/Refractory, Dedifferentiated Liposarcoma (DLPS): an Exploratory Phase II Multicenter Trial
Baseline characteristics by cohort
| Measure |
Plitidepsin
n=24 Participants
plitidepsin
plitidepsin
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=5 Participants
|
|
Age, Continuous
|
63.3 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: 22 patients who completed study i.e who completed one cycle or two incomplete cycles of treatment were analyzed for final efficacy analysis. Out of these 22 patients who completed study, the first 17 patients (first stage of the 2-stage Simon's optimal design ) were analyzed for interim efficacy analysis based on primary endpoint.
Progression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
Outcome measures
| Measure |
Plitidepsin
n=22 Participants
plitidepsin
plitidepsin
|
|---|---|
|
Percentage of Patients Remaining Alive and Progression Free at 3 Months (i.e. Week 12 ± 1) as Per RECIST1.1 (PFS3).
Final efficacy analysis
|
9.1 percentage of participants
Interval 1.1 to 29.2
|
|
Percentage of Patients Remaining Alive and Progression Free at 3 Months (i.e. Week 12 ± 1) as Per RECIST1.1 (PFS3).
Interim analysis population
|
5.9 percentage of participants
Interval 0.15 to 28.7
|
SECONDARY outcome
Timeframe: 6 monthsObjective response assessed as per New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Plitidepsin
n=22 Participants
plitidepsin
plitidepsin
|
|---|---|
|
Percentage of Patients With Objective Response at Six Months (as Per RECIST v1.1)
|
0 percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 6 monthsProgression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
Outcome measures
| Measure |
Plitidepsin
n=22 Participants
plitidepsin
plitidepsin
|
|---|---|
|
Percentage of Patients Remaining Alive and Progression Free at 6 Months as Per RECIST1.1.
|
0 percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: from start of study treatment to the end of the study (up to 10 months)Progression-free survival is defined as the delay between the start date of treatment and the date of progression or death (from any cause), whichever occurs first. Patients alive and progression free were censored at the date of last follow-up, death, or last patient contact. Progression is assessed as per RECIST v1.1.
Outcome measures
| Measure |
Plitidepsin
n=22 Participants
plitidepsin
plitidepsin
|
|---|---|
|
Progression-free Survival
|
1.6 months
Interval 1.4 to 2.6
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
Plitidepsin
n=22 Participants
plitidepsin
plitidepsin
|
|---|---|
|
1-year Overall Survival (OS) Rate
|
40.9 percentage of overall survival
Interval 20.9 to 60.1
|
SECONDARY outcome
Timeframe: through study completion, an average of 1 yearToxicity were graded according to the NCI-CTCAE version 4.0.
Outcome measures
| Measure |
Plitidepsin
n=24 Participants
plitidepsin
plitidepsin
|
|---|---|
|
Treatment Safety (AEs, SAEs and Laboratory Abnormalities) Graded According to the NCI-CTCAE Version 4.0.
|
232 adverse events
|
SECONDARY outcome
Timeframe: through study completion, an average of 1 yearPopulation: 19 patients (out of the 22 patients) for whom translational research have been performed.
Genomic status of biomarkers obtained by using array-comparative genomic hybridization.
Outcome measures
| Measure |
Plitidepsin
n=19 Participants
plitidepsin
plitidepsin
|
|---|---|
|
Number of Participants With a Biomarker Amplification
|
2 participants
|
Adverse Events
Plitidepsin
Serious adverse events
| Measure |
Plitidepsin
n=24 participants at risk
plitidepsin
plitidepsin
|
|---|---|
|
Metabolism and nutrition disorders
ASTHENIA, ANOREXIA, NAUSEA
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Diabetic decompensation
|
4.2%
1/24
|
|
Investigations
CPK increased
|
4.2%
1/24
|
|
Vascular disorders
Inferior vena cava thrombosis
|
4.2%
1/24
|
|
General disorders
SUDDEN DEATH
|
4.2%
1/24
|
|
Investigations
CHEST PAIN / TROPONIN INCREASED
|
4.2%
1/24
|
|
Injury, poisoning and procedural complications
LEFT FOREARM FRACTURE
|
4.2%
1/24
|
|
General disorders
WORSENING OF GENERAL STATUS
|
4.2%
1/24
|
|
Gastrointestinal disorders
NAUSEA
|
8.3%
2/24
|
|
Gastrointestinal disorders
FEVER VOMITING
|
4.2%
1/24
|
|
Infections and infestations
PNEUMONIA
|
4.2%
1/24
|
|
Gastrointestinal disorders
ABDOMINAL PAIN DIARRHEA NAUSEA VOMITING
|
4.2%
1/24
|
|
Infections and infestations
SEPSIS
|
4.2%
1/24
|
|
Blood and lymphatic system disorders
ANEMIA
|
4.2%
1/24
|
|
Immune system disorders
HYPERSENSITIVITY
|
4.2%
1/24
|
|
Gastrointestinal disorders
NAUSEA VOMITING DYSPNEA
|
4.2%
1/24
|
|
Vascular disorders
BILATERAL PULMONARY EMBOLISM
|
4.2%
1/24
|
Other adverse events
| Measure |
Plitidepsin
n=24 participants at risk
plitidepsin
plitidepsin
|
|---|---|
|
Blood and lymphatic system disorders
ANEMIA
|
29.2%
7/24
|
|
Gastrointestinal disorders
Abdominal distension
|
12.5%
3/24
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
3/24
|
|
Gastrointestinal disorders
CONSTIPATION
|
16.7%
4/24
|
|
Gastrointestinal disorders
DIARRHEA
|
41.7%
10/24
|
|
Gastrointestinal disorders
NAUSEA
|
79.2%
19/24
|
|
Gastrointestinal disorders
VOMITING
|
29.2%
7/24
|
|
General disorders
EDEMA LIMBS
|
25.0%
6/24
|
|
General disorders
FATIGUE
|
91.7%
22/24
|
|
General disorders
FEVER
|
20.8%
5/24
|
|
General disorders
INFUSION RELATED REACTION
|
8.3%
2/24
|
|
General disorders
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER
|
8.3%
2/24
|
|
Infections and infestations
LUNG INFECTION
|
8.3%
2/24
|
|
Injury, poisoning and procedural complications
FRACTURE
|
8.3%
2/24
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
8.3%
2/24
|
|
Investigations
ALKALINE PHOSPHATASE INCREASED
|
8.3%
2/24
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
8.3%
2/24
|
|
Investigations
CARDIAC TROPONINE T INCREASED
|
12.5%
3/24
|
|
Investigations
CPK INCREASED
|
8.3%
2/24
|
|
Investigations
GGT INCREASED
|
12.5%
3/24
|
|
Investigations
WEIGHT LOSS
|
16.7%
4/24
|
|
Investigations
INVESTIGATIONS OTHER
|
8.3%
2/24
|
|
Metabolism and nutrition disorders
ANOREXIA
|
54.2%
13/24
|
|
Metabolism and nutrition disorders
DEHYDRATATION
|
8.3%
2/24
|
|
Metabolism and nutrition disorders
HYPOALBUMINEMIA
|
12.5%
3/24
|
|
Metabolism and nutrition disorders
HYPOCALCEMIA
|
8.3%
2/24
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
8.3%
2/24
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
20.8%
5/24
|
|
Nervous system disorders
HEADACHE
|
12.5%
3/24
|
|
Nervous system disorders
NERVOUS SYSTEM DISORDERS OTHER
|
8.3%
2/24
|
|
Psychiatric disorders
INSOMNIA
|
8.3%
2/24
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNEA
|
20.8%
5/24
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY THORACIC AND MEDIASTINAL DISORDERS OTHER
|
8.3%
2/24
|
|
Vascular disorders
THROMBOEMBOLIC EVENT
|
8.3%
2/24
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60