Phase I, Multicenter, Open-label, Dose-escalating, Clinical and Pharmacokinetic Study of PM01183 in Patients With Advanced Solid Tumors

November 3, 2015 updated by: PharmaMar
This is a phase I, multicenter, open-label, dose escalating clinical and pharmacokinetic study of PM01183 for patients with advanced solid tumors

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase I, multicenter, open-label, dose escalating clinical and pharmacokinetic study of PM01183 for patients with advanced solid tumors to identify the dose limiting toxicities (DLTs), determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 administered every three weeks intravenously (i.v.) over one hour to patients with advanced solid tumors and to preliminarily determine the pharmacokinetics of PM01183, to evaluate the antitumor activity of PM01183 and the safety and tolerability of PM01183. Besides this study will evaluate the pharmacogenomics in tumor samples and peripheral white blood cells (PWBCs) of patients exposed to PM01183 at the RD in order to assess potential markers of response and/or resistance.

Study Type

Interventional

Enrollment (Actual)

30

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
      • Barcelona, Spain, 08035
        • Vall d'Hebron University Hospital.
  • United States
    • Illinois
      • Chicago,, Illinois, United States, 60637
        • Cancer Research Center. University of Chicago 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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Voluntary written informed consent of the patient obtained before any study-specific procedure.
  2. Patients with histologically/cytologically confirmed diagnosis of advanced solid tumors refractory to standard therapy or for whom no standard therapy exist (excluding primary central nervous system tumors).
  3. Age ≥ 18 years.
  4. Patients with measurable or non-measurable disease according to RECIST.

  5. Patients entered at the expansion cohort of the RD must have:

    • Measurable disease according to RECIST and/or, evaluable disease by serum markers in the case of prostate and ovarian cancer [according to the Prostate-Specific Antigen Working Group Recommendations (PSAWGR) and the Gynecologic Cancer Intergroup (GCIG) specific criteria, respectively].
    • Confirmed progressive disease after last therapy, before study initiation.
    • Available tumor samples (if pharmacogenomic study consented).
  6. Recovery from any drug-related adverse event derived from any previous treatment, excluding alopecia and grade ≤ 1 asymptomatic peripheral neuropathy according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.3.0.

  7. Laboratory values within seven days prior to first infusion:

    • Platelet count ≥ 100 x109/l, hemoglobin > 9 g/dl (patients can be transfused as clinically indicated prior to study entry) and absolute neutrophils count (ANC) ≥ 1.5 x109/l.
    • Alkaline phosphatase ≤ 2.5 x the upper limit of normality (ULN)
    • Aspartate aminotransferase (AST) ≤ 2.5 x ULN.
    • Alanine aminotransferase (ALT) ≤ 2.5 x ULN.
    • Total bilirubin ≤ ULN. f) Calculated creatinine clearance: ≥ 40 ml/min (calculated using the Cockcroft and Gault formula).
    • Albumin ≥ 2.5 g/dl.
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  8. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both men and women must agree to use a medically acceptable method of contraception throughout the treatment period and for 6 months after discontinuation of treatment. Acceptable methods of contraception include: intrauterine conceptive device (IUD), oral contraceptives, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository).

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. Less than three weeks from radiation therapy (six weeks in case of extensive prior radiotherapy) or last dose of hormonal therapy, biological therapy or chemotherapy (six weeks in case of nitrosoureas, mitomycin C, trastuzumab, bicalutamide or high-dose chemotherapy).
  3. Evidence of progressive Central Nervous System (CNS) metastases or any symptomatic brain or leptomeningeal metastases.
  4. Patients for whom non-standard surgery approach may result in tumor free survival or significant palliation.

  5. Other relevant diseases or adverse clinical conditions:

    • Increased cardiac risk: symptomatic and/or medication requiring congestive heart failure or clinically relevant valvular heart disease or unstable angor pectoris or myocardial infarction within 12 months before inclusion in the study, or ≥ grade 1 arrhythmia or any grade requiring treatment, or uncontrolled arterial hypertension (≥ 160/100 mmHg) despite optimal medical therapy.
    • History of significant neurological or psychiatric disorders.
    • Active infection.
    • Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).
    • Immunocompromised patients, including those known to be infected by human immunodeficiency virus (HIV).
    • Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
  6. Limitation of the patient's ability to comply with the treatment or to follow-up at a participating protocol. Patients registered on this trial must be treated and followed at a participating center.
  7. Prior treatment with any investigational product in the period ≥ 5 half-lives of the investigational compound prior to the first infusion.
  8. Known hypersensitivity to any of the components of the drug product.

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
PM01183 administered i.v. over one hour, on Day 1, every three weeks, at a starting dose of 20 µg/m2.
Drug: PM01183
Vials containing 0.2 mg of PM01183 as powder for concentrate for solution for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To identify the dose limiting toxicities (DLTs), determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 administered every three weeks intravenously (i.v.) over one hour to patients with advanced solid tumors.
Time Frame: Along the study
Along the study

Secondary Outcome Measures

Outcome Measure
Time Frame
To preliminarily determine: pharmacokinetics, antitumor activity and safety of PM01183 and to determine pharmacogenomics in tumor samples and peripheral white blood cells (PWBCs) at the RD
Time Frame: Along the study
Along the study

Collaborators and Investigators

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

Sponsor

PharmaMar

Investigators

  • Principal Investigator: Mark Ratain, MD, Cancer Research Center. University of Chicago Hospitals.
  • Principal Investigator: Josep Tabernero, MD, Vall d'Hebron University Hospital. Barcelona (Spain)

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

March 1, 2009

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

April 6, 2009

First Submitted That Met QC Criteria

April 6, 2009

First Posted (Estimate)

April 7, 2009

Study Record Updates

Last Update Posted (Estimate)

November 4, 2015

Last Update Submitted That Met QC Criteria

November 3, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PM1183-A-001-08

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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