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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
PharmaMar
ClinicalTrials.gov Identifier:
NCT00877474
First received: April 6, 2009
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

This is a phase I, multicenter, open-label, dose escalating clinical and pharmacokinetic study of PM01183 for patients with advanced solid tumors


Condition Intervention Phase
ADVANCED SOLID TUMORS
Drug: PM01183
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I, Multicenter, Open-label, Dose-escalating, Clinical and Pharmacokinetic Study of PM01183 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by PharmaMar:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: March 2009
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00877474

Locations
United States, Illinois
Cancer Research Center. University of Chicago Hospitals.
Chicago,, Illinois, United States, 60637
Spain
Vall d'Hebron University Hospital.
Barcelona, Spain, 08035
Sponsors and Collaborators
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)
  More Information

No publications provided

Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT00877474     History of Changes
Other Study ID Numbers: PM1183-A-001-08
Study First Received: April 6, 2009
Last Updated: November 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by PharmaMar:
PM01183
Solid tumors
PharmaMar USA

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014