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Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination with Fixed Doxorubicin in Non- Heavily Pretreated Patients with Selected Advanced Solid Tumors to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with doxorubicin, to characterize the safety profile and feasibility of this combination, to characterize the pharmacokinetics (PK) of this combination, to obtain preliminary information on the clinical antitumor activity,to explore the feasibility, safety and efficacy of a potential improvable dose of this combination in selected tumor types [i.e. small cell lung cancer (SCLC) and endometrial cáncer] and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed to PM01183 and doxorubicin at the RD in order to assess potential markers of response and/or resistance.
The study has currently met its primary end point and is now recruiting patients to be treated at the RD expansion cohort of selected tumor types, specifically: endometrial adenocarcinomas, neuroendocrine tumors, and small-cell lung cancer (SCLC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| lurbinectedin (PM01183) / doxorubicin | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lurbinectedin (PM01183) | Drug | lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) | A minimum of three patients will be included at each DL. If no patients experience a DLT during Cycle 1, the dose will be escalated. If one of three patients experiences a DLT, three additional patients will be included at that level. If >1 evaluable patient during dose escalation at a given DL experience a DLT during Cycle 1, that DL will be considered the MTD and dose escalation will be terminated, except if all DLTs are related to neutropenia exclusively, in which case dose escalation may be resumed as originally planned in a new cohort of patients but with compulsory primary G-CSF prophylaxis. | During the first cycle of treatment, up to 28 days |
| Recommended Dose (RD) | The DL immediately below the MTD, or DL4 if the MTD is not yet defined during dose escalation before the last DL (i.e., DL4) is reached, was to be initially expanded up to a minimum of nine evaluable patients. If less than three among the first nine evaluable patients treated within the expansion cohort experience a DLT during Cycle 1, this DL will be the RD. | During the first cycle of treatment, up to 28 days |
| Number of Participants With Dose-limiting Toxicities | DLT,dose-limiting toxicity Patients enrolled into this study were originally not allowed to receive primary G-CSF prophylaxis. However, the finding of dose-limiting febrile neutropenia in two patients treated at dose level I in the present study (see below) suggested that increasing doses of the DOX/PM01183 combination might require primary G-CSF prophylaxis to decrease the risk of febrile neutropenia. Therefore, a separate dose escalation was established to define the MTD and the RD of the DOX/PM01183 combination with compulsory primary G-CSF prophylaxis. | During the first cycle of treatment, up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Tumor Response | Tumor response was evaluated according to the RECIST v.1.1 for target lesions and assessed by computed tomography (CT) scans or magnetic resonance imagings (MRIs): Progressive disease (PD) is declared when there is an increase in sum of target disease ≥ 20%, stable diease (SD) when the change is > -30% and ≤ 20%, partial response (PR) when there is a decrease in sum of target disease ≥ 30%, and complete response (CR) when all lesions have disappeared or all lesions have disapeared and all nodal disease is < 10 mm each. |
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Inclusion Criteria:
Voluntarily written informed consent
Age: between 18 and 75 years (both inclusive).
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1. Cohort of patients with SCLC and endometrial cáncer ECOG PS ≤ 2.
Life expectancy ≥ 3 months.
Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors:
At least three weeks since the last anticancer therapy, including radiotherapy
Adequate bone marrow, renal, hepatic, and metabolic function
Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within normal range (according to institutional standards).
Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment
Exclusion Criteria:
Concomitant diseases/conditions:
Brain metastases or leptomeningeal disease involvement.
Men or women of childbearing potential who are not using an effective method of contraception
Patients who have had radiation therapy in more than 35% of the bone marrow. This criterion will not apply to cohort of patients with SCLC and endometrial cáncer.
History of previous bone marrow and/or stem cell transplantation.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitari Vall D'Hebron | Barcelona | 08035 | Spain | |||
| Centro Oncológico Md Anderson International España |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33704620 | Derived | Olmedo ME, Forster M, Moreno V, Lopez-Criado MP, Brana I, Flynn M, Doger B, de Miguel M, Lopez-Vilarino JA, Nunez R, Kahatt C, Cullell-Young M, Zeaiter A, Calvo E. Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study. Invest New Drugs. 2021 Oct;39(5):1275-1283. doi: 10.1007/s10637-020-01025-x. Epub 2021 Mar 11. |
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Screening details:
Age 18-75;CI signed;ECOG PS≤1;histologically/cytologically confirmed diagnosis of advanced disease;Life expectancy≥3 months;not previously treated with anthracycline-containing therapy for advanced disease;No more than two prior lines of cytotoxic-containing chemotherapy regimens;CPK≤2.5xULN;Albumin≥2.5 g/dL
122 patients were enrolled at 7 sites. 120 patients were treated with DOX/PM01183 combination: 73 Cohort A (DOX [mg/m2]+PM01183 [mg FD]) & 47 Cohort B (DOX [mg/m2]+PM01183 [mg/m2]).
Patients participated between 25May2011-9Aug2017 (last followup). First dose of the first cycle was given on 13Jun2011 and last dose of the last cycle on 19Jul2017
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A | DOX: 50 mg/m² q3wk immediately followed by PM01183. The dose escalation scheme was: 3.0, 3.5, 5.0, 6.0, 7.0 mg FD lurbinectedin (PM01183): lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. Doxorubicin: Commercially available presentations of vials containing doxorubicin will be provided as appropriate. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 17, 2014 | Jan 17, 2020 |
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| Doxorubicin | Drug | Commercially available presentations of vials containing doxorubicin will be provided as appropriate. |
|
| Tumor assessments were done every six weeks up to study completion |
| Duration of Response | The duration of overall response was measured from the time measurement criteria are met for complete response (CR)/ PR, whichever is first recorded, until the first date in which progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or the date of death. In absence of disease progression or death, the duration of response was censored on the date of last tumor evaluation. | Time from the time measurement criteria are met for complete response, whichever is first recorded, until the first date in which progressive disease is objectively documented or the date of death, assessed up to 72 months |
| Progression-free Survival | Progression-free survival (PFS) is defined as the time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death has not occurred at the time of the analysis, the PFS was censored on the date of last tumor evaluation. | Time from the date of first administration to the date of PD or death (of any cause), whichever came first, assessed up to 72 months |
| Overall Survival | Overall survival (OS) is defined as the time from the date of first infusion of study treatment to the date of death (due to any cause). Patients with no documented death were censored at the last date they are known to be alive | Time from the date of first administration to the date of death (of any cause), assessed up to 72 months |
| Madrid |
| 28033 |
| Spain |
| Hospital Ramón Y Cajal | Madrid | 28034 | Spain |
| Hospital Universitario Fundación Jiménez | Madrid | 28040 | Spain |
| Hospital Universitario Madrid Sanchinarro | Madrid | 28050 | Spain |
| Fundación Instituto Valenciano de Oncología | Valencia | 46009 | Spain |
| UCLH (University College London Hospitals) | London | WC1E 6DB | United Kingdom |
| FG001 | Cohort B: SCLC 2nd Line | Patients with SCLC 2nd line received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. lurbinectedin (PM01183): lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. Doxorubicin: Commercially available presentations of vials containing doxorubicin will be provided as appropriate. SCLC, small cell lung cancer |
| FG002 | Cohort B: Endometrial | Patients with endometrial cancer received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. lurbinectedin (PM01183): lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. Doxorubicin: Commercially available presentations of vials containing doxorubicin will be provided as appropriate. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A | DOX: 50 mg/m² q3wk immediately followed by PM01183. The dose escalation scheme was: 3.0, 3.5, 5.0, 6.0, 7.0 mg FD |
| BG001 | Cohort B: SCLC 2nd Line | Patients with SCLC 2nd line received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 Immediately followed by PM01183: 2.0 mg/m2. |
| BG002 | Cohort B: Endometrial | Patients with endometrial cancer received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| ECOG PS | ECOG PS, Eastern Cooperative Oncology Group performance status PS 0 Fully active able to carry on all pre-disease performance without restriction PS 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature PS 2 Ambulatory and capable of all selfcare but unable to carry out any work activities up and about more than 50% of waking hours PS 3 Capable of only limited selfcare confined to bed or chair more than 50% of waking hours PS 4 Completely disabled cannot carry on any selfcare; totally confined to bed or chair PS 5 Dead | Count of Participants | Participants |
| |||||||||||||||
| Tumor type | ET-GEP, neuroendocrine-gastroenteropancreatic tumor; SCLC, small cell lung cancer; STS, soft tissue sarcoma; HCC, hepatocellular carcinoma | Count of Participants | Participants |
| |||||||||||||||
| Lines of prior anticancer therapies | Count of Participants | Participants |
| ||||||||||||||||
| Body surface area | Median | Full Range | m^2 |
| |||||||||||||||
| Time from diagnosis to first infusion | Median | Full Range | months |
| |||||||||||||||
| Time from last progressive disease to first infusion | Median | Full Range | months |
| |||||||||||||||
| Time to progression of last prior therapy | Median | Full Range | months |
| |||||||||||||||
| Sites of disease at baseline | Median | Full Range | number of sites |
| |||||||||||||||
| Lines of prior anticancer therapies | Median | Full Range | lines of therapies |
| |||||||||||||||
| Agents of prior anticancer therapies | Median | Full Range | Agents therapies |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) | A minimum of three patients will be included at each DL. If no patients experience a DLT during Cycle 1, the dose will be escalated. If one of three patients experiences a DLT, three additional patients will be included at that level. If >1 evaluable patient during dose escalation at a given DL experience a DLT during Cycle 1, that DL will be considered the MTD and dose escalation will be terminated, except if all DLTs are related to neutropenia exclusively, in which case dose escalation may be resumed as originally planned in a new cohort of patients but with compulsory primary G-CSF prophylaxis. | Fifty-seven of the 61 patients treated in this cohort without primary G-CSF prophylaxis were evaluable for DLTs Eleven of the 12 patients treated with primary G-CSF prophylaxis in this cohort were evaluable for DLTs. | Posted | Number | DOX mg/m2 PM01183 mg FD | During the first cycle of treatment, up to 28 days |
|
|
| ||||||||||||||||||||||||||||||||||||
| Primary | Recommended Dose (RD) | The DL immediately below the MTD, or DL4 if the MTD is not yet defined during dose escalation before the last DL (i.e., DL4) is reached, was to be initially expanded up to a minimum of nine evaluable patients. If less than three among the first nine evaluable patients treated within the expansion cohort experience a DLT during Cycle 1, this DL will be the RD. | Fifty-seven of the 61 patients treated in this cohort without primary G-CSF prophylaxis were evaluable for DLTs | Posted | Number | DOX mg/m2 PM01183 mg FD | During the first cycle of treatment, up to 28 days |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Dose-limiting Toxicities | DLT,dose-limiting toxicity Patients enrolled into this study were originally not allowed to receive primary G-CSF prophylaxis. However, the finding of dose-limiting febrile neutropenia in two patients treated at dose level I in the present study (see below) suggested that increasing doses of the DOX/PM01183 combination might require primary G-CSF prophylaxis to decrease the risk of febrile neutropenia. Therefore, a separate dose escalation was established to define the MTD and the RD of the DOX/PM01183 combination with compulsory primary G-CSF prophylaxis. | Patients evaluable for the primary endpoint (evaluable for DLT): 5 patients were not evaluable in Cohort A and 1 patient in Cohort B. | Posted | Count of Participants | Participants | During the first cycle of treatment, up to 28 days |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Best Overall Tumor Response | Tumor response was evaluated according to the RECIST v.1.1 for target lesions and assessed by computed tomography (CT) scans or magnetic resonance imagings (MRIs): Progressive disease (PD) is declared when there is an increase in sum of target disease ≥ 20%, stable diease (SD) when the change is > -30% and ≤ 20%, partial response (PR) when there is a decrease in sum of target disease ≥ 30%, and complete response (CR) when all lesions have disappeared or all lesions have disapeared and all nodal disease is < 10 mm each. | Cohort A: 1 patient of 73 was not evaluable: extensive bone marrow involvement | Posted | Count of Participants | Participants | Tumor assessments were done every six weeks up to study completion |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Response | The duration of overall response was measured from the time measurement criteria are met for complete response (CR)/ PR, whichever is first recorded, until the first date in which progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or the date of death. In absence of disease progression or death, the duration of response was censored on the date of last tumor evaluation. | Cohort A: 26 patients showed response to treatment Events: 26 (100.0%) Cohort B SCLC: 10 patients showed response to treatment Events: 10 (100.0%) Cohort B: Endometrial: 8 patients showed response to treatment Events: 4 (50.0%) | Posted | Median | 95% Confidence Interval | months | Time from the time measurement criteria are met for complete response, whichever is first recorded, until the first date in which progressive disease is objectively documented or the date of death, assessed up to 72 months |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival | Progression-free survival (PFS) is defined as the time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death has not occurred at the time of the analysis, the PFS was censored on the date of last tumor evaluation. | Cohort A: 1 patient was not evaluable: extensive bone marrow involvement Events: 66 (91.7%) Cohort B: SCLC Events: 28 (100.0%) Cohort B: Endometrial: Events: 14 (73.7%) | Posted | Median | 95% Confidence Interval | months | Time from the date of first administration to the date of PD or death (of any cause), whichever came first, assessed up to 72 months |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival | Overall survival (OS) is defined as the time from the date of first infusion of study treatment to the date of death (due to any cause). Patients with no documented death were censored at the last date they are known to be alive | Cohort A: Events: 15 (20.5%); Cohort B: SCLC: Events: 22 (78.6%); Cohort B: Endometrial Events: 11 (57.9%) | Posted | Median | 95% Confidence Interval | months | Time from the date of first administration to the date of death (of any cause), assessed up to 72 months |
|
Participants were assessed through study completion, approximately 6 years
All 120 patients treated in this study were evaluable for safety
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A | 73 patients treated in Cohort A (DOX [mg/m2] plus PM01183 [mg FD]) were evaluable for safety | 15 | 73 | 47 | 73 | 73 | 73 |
| EG001 | Cohort B: SCLC 2nd Line | Patients with SCLC 2nd line received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. | 22 | 28 | 19 | 28 | 28 | 28 |
| EG002 | Cohort B: Endometrial | Patients with endometrial cancer received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. | 11 | 19 | 14 | 19 | 18 | 19 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deep vein thrombosis | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Venous thrombosis | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Acute monocytic leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hepatic rupture | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
| |
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hydrocephalus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Trigeminal nerve disorder | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Calculus ureteric | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Escherichia sepsis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Hepatitis B | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Neutropenic infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Oesophageal candidiasis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Oral fungal infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Otitis media acute | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotensions | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Infusion site reaction | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (14.1) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Conjunctivitis | Eye disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Anal fissure | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Faecal incontinence | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Onychomycosis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Vulvovaginal candidiasis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Muscle contracture | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Ageusia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Aphonia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Cerebellar ataxia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Intention tremor | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Vaginal discharge | Reproductive system and breast disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Dyspnoea paroxysmal nocturnal | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Nail ridging | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Palmar-plantar erythrodyaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Purpura | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
| |
| Thrombophlebitis | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
|
None reported
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pharma Mar S.A. | Pharma Mar S.A. | 0034918466000 | clinicaltrials@pharmamar.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 12, 2018 | Jan 17, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| C568606 | PM 01183 |
| D004317 | Doxorubicin |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Race : Asian/oriental |
|
| Race : Black |
|
| PS 1 |
|
| PS 2 |
|
| SCLC 3 line |
|
| Endometrial |
|
| NET-GEP |
|
| STS |
|
| Bladder |
|
| Gastric |
|
| Breast |
|
| Ovarian |
|
| HCC |
|
| 1 line |
|
| 2 lines |
|
| 3 lines |
|
| >3 lines |
|
|
| OG003 | Cohort A: Dose III Without Primary G-CSF Prophylaxis | DOX 50 mg/m2 plus PM01183 4.0 mg FD without primary G-CSF prophylaxis |
| OG004 | Cohort A: Dose IV Without Primary G-CSF Prophylaxis | DOX 50 mg/m2 plus PM01183 5.0 mg FD without primary G-CSF prophylaxis |
| OG005 | Cohort A: Dose I With Primary G-CSF Prophylaxis | DOX 50 mg/m2 plus PM01183 3.5 mg FD. Patients enrolled into this study were originally not allowed to receive primary G-CSF prophylaxis. However, the finding of dose-limiting febrile neutropenia in two patients treated at dose level I (DOX 50 mg/m2 plus PM01183 3.5 mg FD) in the present study suggested that increasing doses of the DOX/PM01183 combination might require primary G-CSF prophylaxis to decrease the risk of febrile neutropenia. Therefore, a separate dose escalation was established to define the MTD and the RD of the DOX/PM01183 combination with compulsory primary G-CSF prophylaxis |
| OG006 | Cohort A: Dose III With Primary G-CSF Prophylaxis | DOX 50 mg/m2 plus PM01183 4.0 mg FD Patients enrolled into this study were originally not allowed to receive primary G-CSF prophylaxis. However, the finding of dose-limiting febrile neutropenia in two patients treated at dose level I (DOX 50 mg/m2 plus PM01183 3.5 mg FD) in the present study suggested that increasing doses of the DOX/PM01183 combination might require primary G-CSF prophylaxis to decrease the risk of febrile neutropenia. Therefore, a separate dose escalation was established to define the MTD and the RD of the DOX/PM01183 combination with compulsory primary G-CSF prophylaxis |
| OG007 | Cohort A: Dose IV With Primary G-CSF Prophylaxis | DOX 50 mg/m2 plus PM01183 5.0 mg FD Patients enrolled into this study were originally not allowed to receive primary G-CSF prophylaxis. However, the finding of dose-limiting febrile neutropenia in two patients treated at dose level I (DOX 50 mg/m2 plus PM01183 3.5 mg FD) in the present study suggested that increasing doses of the DOX/PM01183 combination might require primary G-CSF prophylaxis to decrease the risk of febrile neutropenia. Therefore, a separate dose escalation was established to define the MTD and the RD of the DOX/PM01183 combination with compulsory primary G-CSF prophylaxis |
| OG008 | Cohort B: DOX [mg/m2] Plus PM01183 [mg/m2] | DOX [mg/m2] plus PM01183 [mg/m2] Patient accrual into Cohort B started after the RD for the DOX/PM01183 combination had been defined in Cohort A. The dose evaluated in Cohort B was based on this RD, but the DOX dose was decreased to 40 mg/m2 and the PM01183 dose was changed to a BSA-based dose of 2.0 mg/m2 in order to improve the feasibility of this combination in patients with SCLC treated as second-line therapy and in patients with endometrial cancer. In accordance with the findings obtained in Cohort A, no patients in Cohort B received primary G-CSF prophylaxis. |
|
|
| OG002 | Cohort B: Endometrial | Patients with endometrial cancer received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. lurbinectedin (PM01183): lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. Doxorubicin: Commercially available presentations of vials containing doxorubicin will be provided as appropriate. |
|
|
Patients with SCLC 2nd line received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2.
lurbinectedin (PM01183): lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials.
Doxorubicin: Commercially available presentations of vials containing doxorubicin will be provided as appropriate.
| OG002 | Cohort B: Endometrial | Patients with endometrial cancer received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. lurbinectedin (PM01183): lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. Doxorubicin: Commercially available presentations of vials containing doxorubicin will be provided as appropriate. |
|
|
| OG002 | Cohort B: Endometrial | Patients with endometrial cancer received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. lurbinectedin (PM01183): lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. Doxorubicin: Commercially available presentations of vials containing doxorubicin will be provided as appropriate. |
|
|
| OG002 | Cohort B: Endometrial | Patients with endometrial cancer received the following on Day 1 q3wk (three weeks = one treatment cycle), administered: DOX 40 mg/m2 immediately followed by PM01183: 2.0 mg/m2. lurbinectedin (PM01183): lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. Doxorubicin: Commercially available presentations of vials containing doxorubicin will be provided as appropriate. |
|
|