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

February 24, 2020 updated by: PharmaMar

Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination With Doxorubicin in Non-heavily Pretreated Patients With Selected Advanced Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study has currently met its primary end point and is now recruiting patients to be treated at the RD expansion cohort of selected tumor types, specifically: endometrial adenocarcinomas, neuroendocrine tumors, and small-cell lung cancer (SCLC).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
122

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal
      • Madrid, Spain, 28050
        • Hospital Universitario Madrid Sanchinarro
      • Madrid, Spain, 28033
        • Centro Oncologico MD Anderson International Espana
      • Madrid, Spain, 28040
        • Hospital Universitario Fundación Jiménez
      • Valencia, Spain, 46009
        • Fundación Instituto Valenciano de Oncología
  • United Kingdom
      • London, United Kingdom, WC1E 6DB
        • UCLH (University College London Hospitals)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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:

    1. Breast cancer
    2. Soft-tissue sarcoma
    3. Primary bone sarcomas.
    4. Gynecologic tumors (endometrial adenocarcinomas, epithelial ovarian cancer...)
    5. Hepatocellular carcinoma
    6. Gastroenteropancreatic neuroendocrine tumors
    7. Small cell lung cancer (SCLC)
    8. Gastric cancer
    9. Bladder cancer
    10. Adenocarcinoma of unknown primary site
  • At least three weeks since the last anticancer therapy, including radiotherapy
  • Adequate bone marrow, renal, hepatic, and metabolic function
  • Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within normal range (according to institutional standards).
  • Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: lurbinectedin (PM01183) / doxorubicin
Drug: lurbinectedin (PM01183)
lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials.
Drug: Doxorubicin
Commercially available presentations of vials containing doxorubicin will be provided as appropriate.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: During the first cycle of treatment, up to 28 days
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)
Time Frame: During the first cycle of treatment, up to 28 days
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
Time Frame: During the first cycle of treatment, up to 28 days
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Best Overall Tumor Response
Time Frame: Tumor assessments were done every six weeks up to study completion
Tumor response was evaluated according to the RECIST v.1.1 for target lesions and assessed by computed tomography (CT) scans or magnetic resonance imagings (MRIs): Progressive disease (PD) is declared when there is an increase in sum of target disease ≥ 20%, stable diease (SD) when the change is > -30% and ≤ 20%, partial response (PR) when there is a decrease in sum of target disease ≥ 30%, and complete response (CR) when all lesions have disappeared or all lesions have disapeared and all nodal disease is < 10 mm each.
Tumor assessments were done every six weeks up to study completion
Duration of Response
Time Frame: 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
The duration of overall response was measured from the time measurement criteria are met for complete response (CR)/ PR, whichever is first recorded, until the first date in which progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or the date of death. In absence of disease progression or death, the duration of response was censored on the date of last tumor evaluation.
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 Frame: 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
Progression-free survival (PFS) is defined as the time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death has not occurred at the time of the analysis, the PFS was censored on the date of last tumor evaluation.
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 Frame: Time from the date of first administration to the date of death (of any cause), assessed up to 72 months
Overall survival (OS) is defined as the time from the date of first infusion of study treatment to the date of death (due to any cause). Patients with no documented death were censored at the last date they are known to be alive
Time from the date of first administration to the date of death (of any cause), assessed up to 72 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PharmaMar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 25, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 9, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 9, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 22, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 28, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 9, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 24, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PM1183-A-003-10

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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