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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01970540
Recruitment Status : Completed
First Posted : October 28, 2013
Last Update Posted : August 23, 2017
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Endometrial Adenocarcinomas Neuroendocrine Tumors Small-cell Lung Cancer With Less Than 2 Prior Cytotoxic-containing Lines of Therapy Drug: lurbinectedin (PM01183) Drug: Doxorubicin Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 25, 2011
Actual Primary Completion Date : August 9, 2017
Actual Study Completion Date : August 9, 2017

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Recommended Dose (RD) [ Time Frame: 18 months ]
    The RD will be the highest dose level explored in which less than one third of evaluable patients experience a Dose Limiting Toxicity (DLT) during Cycle 1.

Secondary Outcome Measures :
  1. Pharmacokinetics (PK) characterisation [ Time Frame: 18 months ]
    The dose-exposure relationships for maximum plasma concentration (Cmax) and area under the curve (AUC) will be evaluated.

  2. Pharmacogenomic (PGx) analysis [ Time Frame: 18 months ]
    Pharmacogenomics will be evaluated in order to determine predictive/prognostic markers of response and/or resistance to PM01183 and doxorubicin.

  3. Preliminary antitumor efficacy [ Time Frame: 42 months ]
    Recommended Dose expansion is ongoing in selected tumor types in order to confirm preliminary evidence of activity, specifically the study is recruiting patients with neuroendocrine tumors (NETs), or endometrial adenocarcinomas or SCLC (with less than 2 systemic chemotherapy-containing prior lines of therapy)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01970540

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Hospital Universitari Vall D'Hebron
Barcelona, Spain, 08035
Centro Oncológico Md Anderson International España
Madrid, Spain, 28033
Hospital Ramón Y Cajal
Madrid, Spain, 28034
Hospital Universitario Fundación Jiménez
Madrid, Spain, 28040
Hospital Universitario Madrid Sanchinarro
Madrid, Spain, 28050
Fundación Instituto Valenciano de Oncología
Valencia, Spain, 46009
United Kingdom
UCLH (University College London Hospitals)
London, United Kingdom, WC1E 6DB
Sponsors and Collaborators

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Responsible Party: PharmaMar Identifier: NCT01970540     History of Changes
Other Study ID Numbers: PM1183-A-003-10
First Posted: October 28, 2013    Key Record Dates
Last Update Posted: August 23, 2017
Last Verified: January 2017
Keywords provided by PharmaMar:
Pharma Mar
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Small Cell Lung Carcinoma
Carcinoma, Bronchogenic
Lung Diseases
Respiratory Tract Diseases
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action