Study Escalating Doses of PM01183 in Combination With Fixed Doxorubicin in Patients With Specific Advanced Unresectable Solid Tumors

NCT01970540 | Completed Phase 1 Results

• 1 other identifier: PM1183-A-003-10
• Study Type: interventional
• Target: 122
• Locations: 2 countries
• Sites: 7

Brief Summary

Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination with Fixed Doxorubicin in Non- Heavily Pretreated Patients with Selected Advanced Solid Tumors to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with doxorubicin, to characterize the safety profile and feasibility of this combination, to characterize the pharmacokinetics (PK) of this combination, to obtain preliminary information on the clinical antitumor activity,to explore the feasibility, safety and efficacy of a potential improvable dose of this combination in selected tumor types \[i.e. small cell lung cancer (SCLC) and endometrial cáncer\] and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed to PM01183 and doxorubicin at the RD in order to assess potential markers of response and/or resistance.

Conditions

Endometrial Adenocarcinomas; Neuroendocrine Tumors; Small-cell Lung Cancer With Less Than 2 Prior Cytotoxic-containing Lines of Therapy

Keywords

lurbinectedin; PM01183; tumors; cancer; Pharma Mar

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  A minimum of three patients will be included at each DL. If no patients experience a DLT during Cycle 1, the dose will be escalated. If one of three patients experiences a DLT, three additional patients will be included at that level. If \>1 evaluable patient during dose escalation at a given DL experience a DLT during Cycle 1, that DL will be considered the MTD and dose escalation will be terminated, except if all DLTs are related to neutropenia exclusively, in which case dose escalation may be resumed as originally planned in a new cohort of patients but with compulsory primary G-CSF prophylaxis.

  During the first cycle of treatment, up to 28 days

• Recommended Dose (RD)

  The DL immediately below the MTD, or DL4 if the MTD is not yet defined during dose escalation before the last DL (i.e., DL4) is reached, was to be initially expanded up to a minimum of nine evaluable patients. If less than three among the first nine evaluable patients treated within the expansion cohort experience a DLT during Cycle 1, this DL will be the RD.

  During the first cycle of treatment, up to 28 days

• Number of Participants With Dose-limiting Toxicities

  DLT,dose-limiting toxicity Patients enrolled into this study were originally not allowed to receive primary G-CSF prophylaxis. However, the finding of dose-limiting febrile neutropenia in two patients treated at dose level I in the present study (see below) suggested that increasing doses of the DOX/PM01183 combination might require primary G-CSF prophylaxis to decrease the risk of febrile neutropenia. Therefore, a separate dose escalation was established to define the MTD and the RD of the DOX/PM01183 combination with compulsory primary G-CSF prophylaxis.

  During the first cycle of treatment, up to 28 days

Secondary Outcomes (4)

• Best Overall Tumor Response

  Tumor assessments were done every six weeks up to study completion

• Duration of Response

  Time from the time measurement criteria are met for complete response, whichever is first recorded, until the first date in which progressive disease is objectively documented or the date of death, assessed up to 72 months

• Progression-free Survival

  Time from the date of first administration to the date of PD or death (of any cause), whichever came first, assessed up to 72 months

• Overall Survival

  Time from the date of first administration to the date of death (of any cause), assessed up to 72 months

Study Arms (1)

lurbinectedin (PM01183) / doxorubicin

EXPERIMENTAL

Drug: lurbinectedin (PM01183); Drug: Doxorubicin

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) / doxorubicin

Doxorubicin DRUG

Commercially available presentations of vials containing doxorubicin will be provided as appropriate.

lurbinectedin (PM01183) / doxorubicin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily written informed consent
• Age: between 18 and 75 years (both inclusive).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1. Cohort of patients with SCLC and endometrial cáncer ECOG PS ≤ 2.
• Life expectancy ≥ 3 months.
• Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors:
• Breast cancer
• Soft-tissue sarcoma
• Primary bone sarcomas.
• Gynecologic tumors (endometrial adenocarcinomas, epithelial ovarian cancer...)
• Hepatocellular carcinoma
• Gastroenteropancreatic neuroendocrine tumors
• Small cell lung cancer (SCLC)
• Gastric cancer
• Bladder cancer
• Adenocarcinoma of unknown primary site

You may not qualify if:

• Concomitant diseases/conditions:
• History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
• Symptomatic or any uncontrolled arrhythmia
• Ongoing chronic alcohol consumption, or cirrhosis
• Active uncontrolled infection.
• Known human immunodeficiency virus (HIV) infection.
• Any other major illness that, in the Investigator's judgment
• Brain metastases or leptomeningeal disease involvement.
• Men or women of childbearing potential who are not using an effective method of contraception
• Patients who have had radiation therapy in more than 35% of the bone marrow. This criterion will not apply to cohort of patients with SCLC and endometrial cáncer.
• History of previous bone marrow and/or stem cell transplantation.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (7)

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

Centro Oncológico Md Anderson International España

Madrid, 28033, Spain

Location

Hospital Ramón Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Fundación Jiménez

Madrid, 28040, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

UCLH (University College London Hospitals)

London, WC1E 6DB, United Kingdom

Location

Related Publications (1)

• Olmedo ME, Forster M, Moreno V, Lopez-Criado MP, Brana I, Flynn M, Doger B, de Miguel M, Lopez-Vilarino JA, Nunez R, Kahatt C, Cullell-Young M, Zeaiter A, Calvo E. Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study. Invest New Drugs. 2021 Oct;39(5):1275-1283. doi: 10.1007/s10637-020-01025-x. Epub 2021 Mar 11.

  PMID: 33704620 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors; Neoplasms

Interventions

PM 01183; Doxorubicin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

None reported

Results Point of Contact

• Title: Pharma Mar S.A.
• Organization: Pharma Mar S.A.

clinicaltrials@pharmamar.com

0034918466000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: October 28, 2013
• Study Start: May 25, 2011
• Primary Completion: August 9, 2017
• Study Completion: August 9, 2017
• Last Updated: March 9, 2020
• Results First Posted: March 9, 2020

Record last verified: 2020-01

Locations

ES (6); GB (1)