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

NCT02454972 | Completed Phase 2 Results

• 1 other identifier: PM1183-B-005-14
• Study Type: interventional
• Target: 345
• Locations: 9 countries
• Sites: 40

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

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Duration of Response

  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

  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

  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)

  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

  At 4 months

Study Arms (1)

lurbinectedin (PM01183)

EXPERIMENTAL

lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion

Drug: lurbinectedin (PM01183)

Interventions

lurbinectedin (PM01183) DRUG

lurbinectedin (PM01183)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (40)

Sarcoma Oncology Research Center, LLC

Santa Monica, California, 90403, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Massachussets General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Centre

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institute for Drug Development, Cancer Therapy & Research Center at University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Hôpital Cochin

Paris, 75014, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Charité Universitätsmedizin Berlin - Campus Benjamin Franklin - Comprehensive Cancer Center

Berlin, 12200, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

Location

Istituto Ortopedico Rizzoli

Bologna, Italy

Location

lstituto Europeo di Oncologia

Milan, 20141, Italy

Location

ASST Monza - Ospedale San Gerardo di Monza Struttura Complessa di Oncologia Medica

Monza, 20090, Italy

Location

AUSL Romagna - Ospedale Santa Maria delle Croci

Ravenna, 48121, Italy

Location

Complexo Hospitalario Universitario de Santiago

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hopsital Universitario Donostia - Donostia Unibertsitate Ospitalea

San Sebastián, Guipúzcoa, 20014, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Complejo Hospitalario De Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Álvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital de Basurto

Bilbao, Vizcaya, 48013, Spain

Location

Complexo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital Universitari Vall D' Hebron

Barcelona, 08035, Spain

Location

Complejo Hospitalario Regional Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Complejo Hospitalario de Especialidades Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Universitari i Polotècnic la Fe

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Skane University Hospital

Lund, 22185, Sweden

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, 6500, Switzerland

Location

UCL Cancer Institute

London, WC1E 6DD, United Kingdom

Location

Related Publications (7)

• Kristeleit R, Leary A, Delord JP, Moreno V, Oaknin A, Castellano D, Shappiro GI, Fernandez C, Kahatt C, Alfaro V, Siguero M, Rueda D, Zeaiter A, Awada A, Santaballa A, Zaman K, Sehouli J, Subbiah V. Lurbinectedin in patients with pretreated endometrial cancer: results from a phase 2 basket clinical trial and exploratory translational study. Invest New Drugs. 2023 Oct;41(5):677-687. doi: 10.1007/s10637-023-01383-2. Epub 2023 Aug 9.

  PMID: 37556023 DERIVED

• 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.

  PMID: 36037567 DERIVED

• 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.

  PMID: 35830841 DERIVED

• 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.

  PMID: 35486638 DERIVED

• 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.

  PMID: 34739582 DERIVED

• 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.

  PMID: 33096421 DERIVED

• 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.

  PMID: 32224306 DERIVED

MeSH Terms

Interventions

PM 01183

Results Point of Contact

• Title: Clinical Development, Department of PharmaMar´s Oncology., Business Unit.
• Organization: Pharma Mar S.A.

clinicaltrials@pharmamar.com

0034 91846 60 00

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2015
• First Posted: May 27, 2015
• Study Start: August 25, 2015
• Primary Completion: September 18, 2020
• Study Completion: September 18, 2020
• Last Updated: March 2, 2023
• Results First Posted: November 22, 2021

Record last verified: 2023-02

Locations

IT (5); GB (1); CH (2); ES (18); DE (2); BE (1); FR (3); US (7); SE (1)