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

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

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

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: lurbinectedin (PM01183)

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).

• Study Type: Interventional
• Enrollment (Actual): 345
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
• France
  • Paris, France, 75014
    • Hopital Cochin
  • Toulouse, France, 31059
    • Institut Claudius Regaud
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany, 13353
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany, 12200
    • Charité Universitätsmedizin Berlin - Campus Benjamin Franklin - Comprehensive Cancer Center
• Italy
  • Bologna, Italy
    • Istituto Ortopedico Rizzoli
  • Milano, Italy, 20141
    • lstituto Europeo di Oncologia
  • Monza, Italy, 20090
    • ASST Monza - Ospedale San Gerardo di Monza Struttura Complessa di Oncologia Medica
  • Ravenna, Italy, 48121
    • AUSL Romagna - Ospedale Santa Maria delle Croci
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Istituto Clinico Humanitas
• Spain
  • A Coruña, Spain, 15006
    • Complexo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d' Hebron
  • Cordoba, Spain, 14004
    • Complejo Hospitalario Regional Reina Sofía
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28050
    • Hospital Universitario Madrid Sanchinarro
  • Malaga, Spain, 29010
    • Complejo Hospitalario de Especialidades Virgen de la Victoria
  • Valencia, Spain, 46026
    • Hospital Universitari i Polotècnic la Fe
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Complexo Hospitalario Universitario De Santiago
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias
  • Guipúzcoa
    • San Sebastián, Guipúzcoa, Spain, 20014
      • Hopsital Universitario Donostia - Donostia Unibertsitate Ospitalea
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Complejo Hospitalario de Navarra
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Hospital Universitario Alvaro Cunqueiro
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto
• Sweden
  • Lund, Sweden, 22185
    • Skane University Hospital
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Istituto Oncologico della Svizzera Italiana (IOSI)
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Centre Hospitalier Universitaire Vaudois
• United Kingdom
  • London, United Kingdom, WC1E 6DD
    • UCL Cancer Institute
• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center, LLC
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Centre
    • Boston, Massachusetts, United States, 02114
      • Massachussets General Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Institute for Drug Development, Cancer Therapy & Research Center at University of Texas Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lurbinectedin (PM01183); lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion	Drug: lurbinectedin (PM01183)

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

Collaborators and Investigators

• Sponsor: PharmaMar

Publications and helpful links

General Publications

• Boni V, Pistilli B, Brana I, Shapiro GI, Trigo J, Moreno V, Castellano D, Fernandez C, Kahatt C, Alfaro V, Siguero M, Zeaiter A, Longo F, Zaman K, Anton A, Paredes A, Huidobro G, Subbiah V. Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study. ESMO Open. 2022 Oct;7(5):100571. doi: 10.1016/j.esmoop.2022.100571. Epub 2022 Aug 28.
• Longo-Munoz F, Castellano D, Alexandre J, Chawla SP, Fernandez C, Kahatt C, Alfaro V, Siguero M, Zeaiter A, Moreno V, Sanz-Garcia E, Awada A, Santaballa A, Subbiah V. Lurbinectedin in patients with pretreated neuroendocrine tumours: Results from a phase II basket study. Eur J Cancer. 2022 Sep;172:340-348. doi: 10.1016/j.ejca.2022.06.024. Epub 2022 Jul 10.
• Subbiah V, Brana I, Longhi A, Boni V, Delord JP, Awada A, Boudou-Rouquette P, Sarantopoulos J, Shapiro GI, Elias A, Ratan R, Fernandez C, Kahatt C, Cullell-Young M, Siguero M, Zeaiter A, Chawla SP. Antitumor Activity of Lurbinectedin, a Selective Inhibitor of Oncogene Transcription, in Patients with Relapsed Ewing Sarcoma: Results of a Basket Phase II Study. Clin Cancer Res. 2022 Jul 1;28(13):2762-2770. doi: 10.1158/1078-0432.CCR-22-0696.
• Fernandez-Teruel C, Fudio S, Lubomirov R. Integrated exposure-response analysis of efficacy and safety of lurbinectedin to support the dose regimen in small-cell lung cancer. Cancer Chemother Pharmacol. 2022 May;89(5):585-594. doi: 10.1007/s00280-021-04366-3. Epub 2021 Nov 5.
• Subbiah V, Paz-Ares L, Besse B, Moreno V, Peters S, Sala MA, Lopez-Vilarino JA, Fernandez C, Kahatt C, Alfaro V, Siguero M, Zeaiter A, Zaman K, Lopez R, Ponce S, Boni V, Arrondeau J, Delord JP, Martinez M, Wannesson L, Anton A, Valdivia J, Awada A, Kristeleit R, Olmedo ME, Rubio MJ, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D' Arcangelo M, Santoro A, Villalobos VM, Sands J, Trigo J. Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment. Lung Cancer. 2020 Dec;150:90-96. doi: 10.1016/j.lungcan.2020.10.003. Epub 2020 Oct 10.
• Trigo J, Subbiah V, Besse B, Moreno V, Lopez R, Sala MA, Peters S, Ponce S, Fernandez C, Alfaro V, Gomez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martinez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D'Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654. doi: 10.1016/S1470-2045(20)30068-1. Epub 2020 Mar 27. Erratum In: Lancet Oncol. 2020 Dec;21(12):e553.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2015
• Primary Completion (Actual): September 18, 2020
• Study Completion (Actual): September 18, 2020

Study Registration Dates

• First Submitted: May 6, 2015
• First Submitted That Met QC Criteria: May 21, 2015
• First Posted (Estimate): May 27, 2015

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 1, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: PM1183-B-005-14