Phase I, Multicenter, Open-label, Dose-escalating, Clinical and Pharmacokinetic Study of PM01183 in Patients With Advanced Solid Tumors

NCT00877474 | Completed Phase 1

• 1 other identifier: PM1183-A-001-08
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a phase I, multicenter, open-label, dose escalating clinical and pharmacokinetic study of PM01183 for patients with advanced solid tumors

Conditions

ADVANCED SOLID TUMORS

Keywords

PM01183; Solid tumors; PharmaMar USA

Outcome Measures

Primary Outcomes (1)

• To identify the dose limiting toxicities (DLTs), determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 administered every three weeks intravenously (i.v.) over one hour to patients with advanced solid tumors.

  Along the study

Secondary Outcomes (1)

• To preliminarily determine: pharmacokinetics, antitumor activity and safety of PM01183 and to determine pharmacogenomics in tumor samples and peripheral white blood cells (PWBCs) at the RD

  Along the study

Study Arms (1)

Arm 1

EXPERIMENTAL

PM01183 administered i.v. over one hour, on Day 1, every three weeks, at a starting dose of 20 µg/m2.

Drug: PM01183

Interventions

PM01183 DRUG

Vials containing 0.2 mg of PM01183 as powder for concentrate for solution for infusion

Arm 1

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent of the patient obtained before any study-specific procedure.
• Patients with histologically/cytologically confirmed diagnosis of advanced solid tumors refractory to standard therapy or for whom no standard therapy exist (excluding primary central nervous system tumors).
• Age ≥ 18 years.
• Patients with measurable or non-measurable disease according to RECIST.
• Patients entered at the expansion cohort of the RD must have:
• Measurable disease according to RECIST and/or, evaluable disease by serum markers in the case of prostate and ovarian cancer \[according to the Prostate-Specific Antigen Working Group Recommendations (PSAWGR) and the Gynecologic Cancer Intergroup (GCIG) specific criteria, respectively\].
• Confirmed progressive disease after last therapy, before study initiation.
• Available tumor samples (if pharmacogenomic study consented).
• Recovery from any drug-related adverse event derived from any previous treatment, excluding alopecia and grade ≤ 1 asymptomatic peripheral neuropathy according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.3.0.
• Laboratory values within seven days prior to first infusion:
• Platelet count ≥ 100 x109/l, hemoglobin \> 9 g/dl (patients can be transfused as clinically indicated prior to study entry) and absolute neutrophils count (ANC) ≥ 1.5 x109/l.
• Alkaline phosphatase ≤ 2.5 x the upper limit of normality (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN.
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN.
• Total bilirubin ≤ ULN. f) Calculated creatinine clearance: ≥ 40 ml/min (calculated using the Cockcroft and Gault formula).

You may not qualify if:

• Pregnant or lactating women.
• Less than three weeks from radiation therapy (six weeks in case of extensive prior radiotherapy) or last dose of hormonal therapy, biological therapy or chemotherapy (six weeks in case of nitrosoureas, mitomycin C, trastuzumab, bicalutamide or high-dose chemotherapy).
• Evidence of progressive Central Nervous System (CNS) metastases or any symptomatic brain or leptomeningeal metastases.
• Patients for whom non-standard surgery approach may result in tumor free survival or significant palliation.
• Other relevant diseases or adverse clinical conditions:
• History of significant neurological or psychiatric disorders.
• Active infection.
• Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).
• Immunocompromised patients, including those known to be infected by human immunodeficiency virus (HIV).
• Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
• Limitation of the patient's ability to comply with the treatment or to follow-up at a participating protocol. Patients registered on this trial must be treated and followed at a participating center.
• Prior treatment with any investigational product in the period ≥ 5 half-lives of the investigational compound prior to the first infusion.
• Known hypersensitivity to any of the components of the drug product.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (2)

Cancer Research Center. University of Chicago Hospitals.

Chicago, Illinois, 60637, United States

Location

Vall d'Hebron University Hospital.

Barcelona, Barcelona, 08035, Spain

Location

Related Publications (2)

• Fernandez-Teruel C, Lubomirov R, Fudio S. Population Pharmacokinetic-Pharmacodynamic Modeling and Covariate Analyses of Neutropenia and Thrombocytopenia in Patients With Solid Tumors Treated With Lurbinectedin. J Clin Pharmacol. 2021 Sep;61(9):1206-1219. doi: 10.1002/jcph.1886. Epub 2021 Jun 9.

  PMID: 33914350 DERIVED

• Elez ME, Tabernero J, Geary D, Macarulla T, Kang SP, Kahatt C, Pita AS, Teruel CF, Siguero M, Cullell-Young M, Szyldergemajn S, Ratain MJ. First-in-human phase I study of Lurbinectedin (PM01183) in patients with advanced solid tumors. Clin Cancer Res. 2014 Apr 15;20(8):2205-14. doi: 10.1158/1078-0432.CCR-13-1880. Epub 2014 Feb 21.

  PMID: 24563480 DERIVED

MeSH Terms

Interventions

PM 01183

Study Officials

• Mark Ratain, MD

  Cancer Research Center. University of Chicago Hospitals.

  PRINCIPAL INVESTIGATOR

• Josep Tabernero, MD

  Vall d'Hebron University Hospital. Barcelona (Spain)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 6, 2009
• First Posted: April 7, 2009
• Study Start: March 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: November 4, 2015

Record last verified: 2015-11

Locations

ES (1); US (1)