- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01970540
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
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
122
Phase
- 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
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Barcelona, Spain, 08035
- Hospital Universitari Vall d'Hebron
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Madrid, Spain, 28034
- Hospital Ramon y Cajal
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Madrid, Spain, 28050
- Hospital Universitario Madrid Sanchinarro
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Madrid, Spain, 28033
- Centro Oncológico MD Anderson International España
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Madrid, Spain, 28040
- Hospital Universitario Fundacion Jimenez
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Valencia, Spain, 46009
- Fundación Instituto Valenciano de Oncología
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London, United Kingdom, WC1E 6DB
- UCLH (University College London Hospitals)
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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
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:
- 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
- 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 |
Intervention / Treatment |
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Experimental: lurbinectedin (PM01183) / doxorubicin
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lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials.
Commercially available presentations of vials containing doxorubicin will be provided as appropriate.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD)
Time Frame: During the first cycle of treatment, up to 28 days
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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.
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During the first cycle of treatment, up to 28 days
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Recommended Dose (RD)
Time Frame: During the first cycle of treatment, up to 28 days
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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.
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During the first cycle of treatment, up to 28 days
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Number of Participants With Dose-limiting Toxicities
Time Frame: During the first cycle of treatment, up to 28 days
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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.
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During the first cycle of treatment, up to 28 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best Overall Tumor Response
Time Frame: Tumor assessments were done every six weeks up to study completion
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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.
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Tumor assessments were done every six weeks up to study completion
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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
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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.
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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
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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
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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.
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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
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Overall Survival
Time Frame: Time from the date of first administration to the date of death (of any cause), assessed up to 72 months
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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
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Time from the date of first administration to the date of death (of any cause), assessed up to 72 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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.
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)
May 25, 2011
Primary Completion (Actual)
August 9, 2017
Study Completion (Actual)
August 9, 2017
Study Registration Dates
First Submitted
October 22, 2013
First Submitted That Met QC Criteria
October 22, 2013
First Posted (Estimate)
October 28, 2013
Study Record Updates
Last Update Posted (Actual)
March 9, 2020
Last Update Submitted That Met QC Criteria
February 24, 2020
Last Verified
January 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Lung Neoplasms
- Small Cell Lung Carcinoma
- Neuroendocrine Tumors
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Doxorubicin
Other Study ID 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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