Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
Multicenter, open-label, exploratory, phase II clinical trial to evaluate the efficacy and safety of PM01183 in previously treated patients with advanced solid tumors

Detailed Description
-----------------
Patients with relapsed small cell lung cancer (SCLC), head and neck carcinoma (H&N), neuroendocrine tumors (NETs), biliary tract carcinoma, endometrial carcinoma, BRCA 1/2-associated metastatic breast carcinoma, carcinoma of unknown primary site, germ cell tumors (GCTs), and Ewing's family of tumors (EFTs) will be enrolled in nine different cohorts. Up to 25 evaluable patients are planned to be enrolled in each cohort (50 in the endometrial carcinoma and 100 in the SCLC cohort).

Official Title
-----------------
A Multicenter Phase II Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors

Conditions
-----------------
Advanced Solid Tumors

Intervention / Treatment
-----------------
* Drug: lurbinectedin (PM01183)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years. Voluntary signed informed consent (IC) Pathologically proven diagnosis of any of the following malignancies: Small cell lung cancer (SCLC). Head and neck carcinoma (H&N). Salivary glands tumors are excluded. Neuroendocrine tumors (NETs), grade 2 and grade 3 according to World Health Organization classification. Biliary tract carcinoma. Endometrial carcinoma. BRCA 1/2- associated metastatic breast carcinoma Carcinoma of unknown primary site. Germ cell tumor (GCTs), excluding immature teratoma, or teratoma with malignant transformation. Ewing's family of tumors (EFTs) Prior treatment. Patients must have received: SCLC, endometrial carcinoma: one prior chemotherapy-containing line. H&N, NETs, biliary tract, CUP: one or two prior chemotherapy-containing lines GCTs: no limit of prior therapy EFTs: no more than two prior chemotherapy-containing lines in the metastatic/recurrent setting. BRCA 1/2-associated metastatic breast carcinoma: at least one but no more than three prior chemotherapy-containing lines. Performance status ≤ 2 [Eastern Cooperative Oncology Group (ECOG)] Adequate major organ function At least three weeks since the last chemotherapy Women of childbearing potential must have pregnancy excluded by appropriate testing before study entry Exclusion Criteria: Prior treatment with PM01183 or trabectedin Prior or concurrent malignant disease unless in complete remission for more than five years Known central nervous system (CNS) involvement Relevant diseases or clinical situations which may increase the patient's risk Pregnant or breastfeeding women and fertile patients (men and women) who are not using an effective method of contraception

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lurbinectedin (PM01183)<br>lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion | Drug: lurbinectedin (PM01183)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall Response Rate was defined as the percentage of patients with a confirmed response, either CR or PR, according to the RECIST v.1.1. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥30% decrease in the sum of the longest diameters of target lesions compared with baseline; Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest; diameter recorded or the appearance of one or more new lesions; Stable Disease: Neither PR or PD | From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle) | 
| Response by Investigator Assessment | When response is the primary endpoint, and thus all patients must have measurable disease to enter the trial, all patients included in the study must be accounted for in the report of the results, even if there are major protocol treatment deviations or if they are not evaluable. Each patient will be assigned one of the following: Complete Response: Disappearance of all target lesions; Partial Response: ≥30% decrease in the sum of the longest diameters of target lesions; Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions; diameter recorded or the appearance of one or more new lesions; Stable Disease: Neither PR or PD; Inevaluable for response: specify reasons (for example: early death, malignant disease, toxicity; tumour assessments not repeated/incomplete; other). Normally, all eligible patients should be included in the denominator for the calculation of the response rate for phase II trials. | From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Duration of Response by Investigator's Assessment, defined as the time between the date when the response criteria (PR or CR, whichever one is first reached) are fulfilled to the first date when disease progression (PD), recurrence or death is documented. | From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle) | 
| Clinical Benefit | Clinical Benefit Rate was defined as Overall Response Rate or Stable Disease lasting over four months (SD ≥ 4 months) | From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle) | 
| Disease Control Rate | Disease Control Rate was defined as Overall Response Rate or Stable Disease | From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 | 
| Progression Free Survival (PFS) | Progression-free Survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (of any cause), or last tumor evaluation. Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest | From the date of first infusion to the date of progression disease, death (of any cause), or last tumor evaluation, up to an average of 5 years | 
| Progression-free Survival at 4 Months | Progression-free Survival at 4, defined as the probability of being free from progression and death after the first infusion at 4 months. Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest | At 4 months | 
| Progression-free Survival at 6 Months | Progression-free Survival at 6, defined as the probability of being free from progression and death after the first infusion at 6 months. Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest | At 6 months | 
| Overall Survival (OS) | Overall survival defined as the period of time from the date of first infusion to the date of death or last contact in case of patients lost to follow-up or alive at the clinical cutoff established for the cohort. | From the date of first infusion to the date of death or last contact, up to an average of 5 years | 
| Overall Survival at 6 Months | Overall Survival at 6 months defined as the probability of being alive after the first infusion at 6 months | At 6 months | 
| Overall Survival at 12 Months | Overall Survival at 12 months defined as the probability of being alive after the first infusion at 12 months | At 12 months |