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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02454972
• Other study ID #: PM1183-B-005-14
• Status: Completed
• Phase: Phase 2
• Start date: August 25, 2015
• Est. completion date: September 18, 2020

Study information

• Verified date: February 2023
• Source: PharmaMar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 345
• Est. completion date: September 18, 2020
• Est. primary completion date: September 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• lurbinectedin (PM01183)

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussels
France	Hôpital Cochin	Paris
France	Institut Claudius Regaud	Toulouse
France	Institut Gustave Roussy	Villejuif
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Charité Universitätsmedizin Berlin - Campus Benjamin Franklin - Comprehensive Cancer Center	Berlin
Italy	Istituto Ortopedico Rizzoli	Bologna
Italy	lstituto Europeo di Oncologia	Milano
Italy	ASST Monza - Ospedale San Gerardo di Monza Struttura Complessa di Oncologia Medica	Monza
Italy	AUSL Romagna - Ospedale Santa Maria delle Croci	Ravenna
Italy	Istituto Clinico Humanitas	Rozzano	Milan
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Universitari Vall D' Hebron	Barcelona
Spain	Hospital de Basurto	Bilbao	Vizcaya
Spain	Complejo Hospitalario Regional Reina Sofía	Cordoba
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Madrid Sanchinarro	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Complejo Hospitalario de Especialidades Virgen de la Victoria	Malaga
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Complejo Hospitalario De Navarra	Pamplona	Navarra
Spain	Hopsital Universitario Donostia - Donostia Unibertsitate Ospitalea	San Sebastián	Guipúzcoa
Spain	Complexo Hospitalario Universitario de Santiago	Santiago de Compostela	A Coruña
Spain	Hospital Universitari i Polotècnic la Fe	Valencia
Spain	Hospital Universitario Álvaro Cunqueiro	Vigo	Pontevedra
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Skane University Hospital	Lund
Switzerland	Istituto Oncologico della Svizzera Italiana (IOSI)	Bellinzona
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud
United Kingdom	UCL Cancer Institute	London
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Beth Israel Deaconess Medical Centre	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachussets General Hospital	Boston	Massachusetts
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Institute for Drug Development, Cancer Therapy & Research Center at University of Texas Health Science Center	San Antonio	Texas
United States	Sarcoma Oncology Research Center, LLC	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
PharmaMar

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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