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

Phase 2

Completed

• Conditions: Advanced Solid Tumors
• Interventions: Drug: lurbinectedin (PM01183)

• Registration Number: NCT02454972
• Lead Sponsor: PharmaMar

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).

Study Timeline

• Study First Submitted: 2015-05-06
• Study First Submitted QC: 2015-05-21
• Study First Posted: 2015-05-27
• Study Start: 2015-08-25
• Primary Completion: 2020-09-18
• Study Completion: 2020-09-18
• Results First Submitted: 2021-09-17
• Results First Submitted QC: 2021-10-21
• Results First Posted: 2021-11-22
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-01
• Last Update Posted: 2023-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 345

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Response by Investigator Assessment	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)	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.
Overall Response Rate (ORR)	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)	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

Secondary Outcome Measures

Name	Time	Method
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)	Clinical Benefit Rate was defined as Overall Response Rate or Stable Disease lasting over four months (SD ≥ 4 months)
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	Disease Control Rate was defined as Overall Response Rate or Stable Disease
Progression-free Survival at 4 Months	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
Progression-free Survival at 6 Months	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
Overall Survival (OS)	From the date of first infusion to the date of death or last contact, up to an average of 5 years	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.
Overall Survival at 12 Months	At 12 months	Overall Survival at 12 months defined as the probability of being alive after the first infusion at 12 months
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)	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.
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 (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
Overall Survival at 6 Months	At 6 months	Overall Survival at 6 months defined as the probability of being alive after the first infusion at 6 months

Trial Locations

Locations (40)

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Hospital Universitario Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen de las Nieves; 🇪🇸 Granada, Spain

Istituto Oncologico della Svizzera Italiana (IOSI); 🇨🇭 Bellinzona, Switzerland

Istituto Ortopedico Rizzoli; 🇮🇹 Bologna, Italy

Complexo Hospitalario Universitario A Coruña; 🇪🇸 A Coruña, Spain

Complejo Hospitalario De Navarra; 🇪🇸 Pamplona, Navarra, Spain

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

lstituto Europeo di Oncologia; 🇮🇹 Milano, Italy

Hôpital Cochin; 🇫🇷 Paris, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France

Hospital Universitario Puerta de Hierro Majadahonda; 🇪🇸 Majadahonda, Madrid, Spain

Hospital Universitari i Polotècnic la Fe; 🇪🇸 Valencia, Spain

Complejo Hospitalario de Especialidades Virgen de la Victoria; 🇪🇸 Malaga, Spain

Massachussets General Hospital; 🇺🇸 Boston, Massachusetts, United States

UCL Cancer Institute; 🇬🇧 London, United Kingdom

Hopsital Universitario Donostia - Donostia Unibertsitate Ospitalea; 🇪🇸 San Sebastián, Guipúzcoa, Spain

Institute for Drug Development, Cancer Therapy & Research Center at University of Texas Health Science Center; 🇺🇸 San Antonio, Texas, United States

Complejo Hospitalario Regional Reina Sofía; 🇪🇸 Cordoba, Spain

Hospital de Basurto; 🇪🇸 Bilbao, Vizcaya, Spain

Hospital Universitario Madrid Sanchinarro; 🇪🇸 Madrid, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Vaud, Switzerland

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

ASST Monza - Ospedale San Gerardo di Monza Struttura Complessa di Oncologia Medica; 🇮🇹 Monza, Italy

Skane University Hospital; 🇸🇪 Lund, Sweden

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Beth Israel Deaconess Medical Centre; 🇺🇸 Boston, Massachusetts, United States

Sarcoma Oncology Research Center, LLC; 🇺🇸 Santa Monica, California, United States

AUSL Romagna - Ospedale Santa Maria delle Croci; 🇮🇹 Ravenna, Italy

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Charité Universitätsmedizin Berlin - Campus Benjamin Franklin - Comprehensive Cancer Center; 🇩🇪 Berlin, Germany

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Milan, Italy

Hospital Universitari Vall D' Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario Álvaro Cunqueiro; 🇪🇸 Vigo, Pontevedra, Spain

Complexo Hospitalario Universitario de Santiago; 🇪🇸 Santiago de Compostela, A Coruña, Spain