Clinical trial NCT02454972: Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors
Official title: A Multicenter Phase II Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Solid Tumors
Lead sponsor: PharmaMar
Sponsor class: INDUSTRY
First posted: 2015-05-27
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 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)
measure: Response by Investigator Assessment
timeFrame: 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:
measure: Duration of Response
timeFrame: 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)
measure: Clinical Benefit
timeFrame: 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)
measure: Disease Control Rate
timeFrame: 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
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Progression-free Survival at 4 Months
timeFrame: At 4 months
measure: Progression-free Survival at 6 Months
timeFrame: At 6 months
measure: Overall Survival (OS)
timeFrame: From the date of first infusion to the date of death or last contact, up to an average of 5 years
measure: Overall Survival at 6 Months
timeFrame: At 6 months
measure: Overall Survival at 12 Months
timeFrame: At 12 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center, LLC
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Boston
country: United States
facility: Massachussets General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Centre
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Institute for Drug Development, Cancer Therapy & Research Center at University of Texas Health Science Center
state: Texas
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Paris
country: France
facility: Hôpital Cochin
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin - Campus Benjamin Franklin - Comprehensive Cancer Center
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
city: Milano
country: Italy
facility: lstituto Europeo di Oncologia
city: Monza
country: Italy
facility: ASST Monza - Ospedale San Gerardo di Monza Struttura Complessa di Oncologia Medica
city: Ravenna
country: Italy
facility: AUSL Romagna - Ospedale Santa Maria delle Croci
city: Santiago de Compostela
country: Spain
facility: Complexo Hospitalario Universitario de Santiago
state: A Coruña
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: San Sebastián
country: Spain
facility: Hopsital Universitario Donostia - Donostia Unibertsitate Ospitalea
state: Guipúzcoa
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Pamplona
country: Spain
facility: Complejo Hospitalario De Navarra
state: Navarra
city: Vigo
country: Spain
facility: Hospital Universitario Álvaro Cunqueiro
state: Pontevedra
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D' Hebron
city: Cordoba
country: Spain
facility: Complejo Hospitalario Regional Reina Sofía
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Malaga
country: Spain
facility: Complejo Hospitalario de Especialidades Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Universitari i Polotècnic la Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Lund
country: Sweden
facility: Skane University Hospital
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
state: Vaud
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana (IOSI)
city: London
country: United Kingdom
facility: UCL Cancer Institute
Study officials:
References:
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.