Study of Lurbinectedin (PM01183) in Combination With Cisplatin in Patients With Solid Tumors

NCT01980667 | Completed Phase 1

• 1 other identifier: PM1183-A-008-13
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 3

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.

Conditions

Advanced Solid Tumors

Keywords

lurbinectedin; PM01183; tumors; cancer; Pharma Mar

Outcome Measures

Primary Outcomes (1)

• Recommended dose (RD) of the combination PM01183 and cisplatin

  To determine the recommended dose (RD) of PM01183 in combination with cisplatin every three weeks (q3wk) with or without aprepitant in patients with advanced solid tumors. The RD will be the dose level (DL) immediately below the maximum tolerated dose (MTD), that is, the highest DL explored at which less than one third of evaluable patients experience a DLT during Cycle 1.

  30 months

Secondary Outcomes (2)

• Pharmacokinetics (PK) characterisation of Cmax (maximum concentratio), AUC (area under the curve), CL (clearance), HL (half life) y Vss (volume of distribution)

  30 months

• Pharmacogenomic (PGx) analysis

  30 months

Study Arms (1)

lurbinectedin (PM01183) / cisplatin

EXPERIMENTAL

Patients will receive cisplatin as a 90-min i.v. infusion. In addition, patients will receive PM01183 as an i.v. infusion over 1-hour.

Drug: lurbinectedin (PM01183); Drug: Cisplatin

Interventions

lurbinectedin (PM01183) DRUG

lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials.

lurbinectedin (PM01183) / cisplatin

Cisplatin DRUG

vials containing 1 mg/ml concentrate for solution for infusion

lurbinectedin (PM01183) / cisplatin

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (3)

Unknown Facility

Bellinzona, Switzerland

Location

Unknown Facility

London, United Kingdom

Location

Unknown Facility

Newcastle, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34453241 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

PM 01183; Cisplatin

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: November 11, 2013
• Study Start: July 30, 2014
• Primary Completion: January 5, 2017
• Study Completion: January 5, 2017
• Last Updated: January 26, 2017

Record last verified: 2017-01

Locations

GB (2); CH (1)