Clinical trial NCT01980667: Study of Lurbinectedin (PM01183) in Combination With Cisplatin in Patients With Solid Tumors
Official title: Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination With Cisplatin in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: lurbinectedin
PM01183
tumors
cancer
Pharma Mar
Lead sponsor: PharmaMar
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 41
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: Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination with Cisplatin in Patients with Advanced Solid Tumors to determine the recommended dose (RD) of PM01183 in combination with cisplatin, to characterize the safety profile, the pharmacokinetics (PK) of this combination, to obtain preliminary information on the clinical antitumor activity and to conduct an exploratory pharmacogenomic (PGx) analysis.


Eligibility criteria: Inclusion Criteria:

* Voluntarily signed written informed consent
* Age ≥ 18 years old
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1.
* Life expectancy ≥ 3 months.
* Patients with confirmed diagnosis of advanced solid tumors.
* Patients may have received ≤ 2 chemotherapy-containing lines in the advanced setting.
* Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ seven days before inclusion in the study)
* Recovery or stabilization to grade ≤ 1 from any adverse event derived from previous treatment (up to grade 2 alopecia or asthenia/fatigue are allowed).
* No clinically significant changes in ECG.
* At least four weeks since the last monoclonal antibody containing therapy or definitive radiotherapy (RT)
* At least two weeks since the last biological/investigational single-agent therapy (excluding MAbs) and/or palliative RT (≤10 fractions or ≤30 Gy total dose)
* Fertil women must have pregnancy excluded by appropriate testing before study entry

Exclusion Criteria:

* Prior treatment with PM01183 or trabectedin.
* Concomitant diseases/conditions:

  * History within the last year or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically relevant valvular heart disease or symptomatic arrhythmia or any asymptomatic ventricular arrhythmia requiring ongoing treatment.
  * Ongoing, non-neoplastic, chronically active liver disease of any origin.
  * Active infection.
  * Patients who are requiring any ongoing oxygen support.
  * Known human immunodeficiency virus (HIV) infection.
  * Any other major illness.
* Symptomatic or corticosteroid-requiring brain metastases or leptomeningeal disease involvement. Patients with asymptomatic documented stable brain metastases not requiring corticosteroids during the last three months are allowed.
* Peripheral sensory/motor neuropathy grade \>1. Hearing impairment grade \>1.
* Fertile men or women not using an effective method of contraception.
* History of bone marrow or stem cell transplantation
* Radiotherapye to \>35% of the bone marrow.

Primary outcomes:
measure: Recommended dose (RD) of the combination PM01183 and cisplatin
timeFrame: 30 months
Secondary outcomes:
measure: Pharmacokinetics (PK) characterisation of Cmax (maximum concentratio), AUC (area under the curve), CL (clearance), HL (half life) y Vss (volume of distribution)
timeFrame: 30 months
measure: Pharmacogenomic (PGx) analysis
timeFrame: 30 months
Other outcomes:
Locations:
city: Bellinzona
country: Switzerland
city: London
country: United Kingdom
city: Newcastle
country: United Kingdom
Study officials:
References:
citation: Metaxas Y, Kahatt C, Alfaro V, Fudio S, Zeaiter A, Plummer R, Sessa C, Von Moos R, Forster M, Stathis A. A phase I trial of lurbinectedin in combination with cisplatin in patients with advanced solid tumors. Invest New Drugs. 2022 Feb;40(1):91-98. doi: 10.1007/s10637-021-01142-1. Epub 2021 Aug 28.