Escalating Doses of PM01183 in Combination With Gemcitabine in Patients With Specific Unresectable Solid Tumors

March 31, 2015 updated by: PharmaMar

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

Phase I multicenter, open-label, clinical and pharmacokinetic study of PM01183 in combination with gemcitabine 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 gemcitabine, to characterize the safety profile and feasibility of this combination in patients with selected advanced solid tumors, to characterize the pharmacokinetics (PK), to obtain preliminary information on the clinical antitumor activity in non-heavily pretreated selected solid tumor patients and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed, in order to assess potential markers of response and/or resistance.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

47

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

  • Spain
      • Madrid, Spain
        • Hospital Universitario Madrid Sanchinarro
      • Seville, Spain
        • Hospital Universitario Virgen del Rocio
  • United Kingdom
      • London, United Kingdom
        • University College of London Hospital

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
  • Life expectancy ≥ 3 months

  • Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors:

    1. Breast cancer
    2. Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas)
    3. Stromal uterine sarcomas
    4. Non-small cell lung cancer (NSCLC)
    5. Platinum-refractory or relapsed germ cell tumors
    6. Adenocarcinoma of the exocrine pancreas
    7. Biliary tract adenocarcinoma
    8. Adenocarcinoma or carcinoma of unknown primary site
    9. Advanced or unresectable mesothelioma
  • At least three weeks since the last anticancer therapy,including radiation therapy (RT)
  • Adequate bone marrow, renal, hepatic, and metabolic function
  • Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) 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
  • History of previous bone marrow and/or stem cell transplantation
  • Prior treatment with gemcitabine-containing therapy for advanced disease

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
Experimental: lurbinectedin (PM01183) / gemcitabine

Patients will consecutively receive the following on Days 1 and 8 q3wk (three weeks = one treatment cycle):

- Gemcitabine: intravenous infusion of 800 mg/m2/day over 30 minutes,

immediately followed by:

- PM01183: intravenous infusion over one hour at a starting dose of 2.5 mg/day, flat dose (FD), both on Days 1 and 8 every 3 weeks
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: Gemcitabine
1000 mg vial, powder for injectable solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended Dose (RD)
Time Frame: 19 months
The RD will be the highest dose level explored at which less than one third of evaluable patients experience a DLT during Cycle 1.
19 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK) characterisation
Time Frame: 19 months
The dose-exposure relationships for maximum plasma concentration (Cmax) and area under the curve (AUC) will be evaluated.
19 months
Preliminary antitumor efficacy
Time Frame: 29 months
To obtain preliminary information on the clinical antitumor activity of this combination in non-heavily pretreated selected solid tumor patients
29 months
Pharmacogenomics (PGx)
Time Frame: 29 months
to identify molecular markers whose expression may be associated with the clinical outcome of patients. These molecular markers might allow the identification of those patients who will benefit from PM01183 and gemcitabine treatment, thus improving the health care by an individualized medicine.
29 months

Collaborators and Investigators

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

Sponsor

PharmaMar

Investigators

  • Study Chair: Sergio Szyldergemajn, MD, Pharma Mar

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

May 1, 2011

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

October 1, 2013

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 (Estimate)

April 1, 2015

Last Update Submitted That Met QC Criteria

March 31, 2015

Last Verified

October 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PM1183-A-004-10

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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