Liposome Encapsulated Docetaxel (LE-DT) in Patients With Solid Tumors (LE-DT)

A Phase 1 Study of Liposome Encapsulated Docetaxel (LE-DT) in Patients With Advanced Solid Tumors

Liposome Encapsulated Docetaxel (LE-DT) is a novel proprietary delivery system of docetaxel developed by NeoPharm, Inc. In this Phase I study, the LE-DT was evaluated for the maximum tolerated dose and dose limiting toxicity (DLT) in patients with advance solid tumors. It was also evaluated for pharmacokinetic and anti-tumor effects.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: LE-DT

Detailed Description

Liposome Entrapped Doxetaxel (LE-DT) is a novel, proprietary delivery system of docetaxel developed by NeoPharm, Inc. Docetaxel (currently marketed as Taxotere®) is an anti-microtubule agent that prevents cell division by promoting the assembly and stabilization of microtubules and is used for the treatment of malignancies from breast, prostate, lung, gastric, head and neck. By removing toxic detergent used in Taxotere®, LE-DT showed reduced toxicity and comparable therapeutic efficacy in preclinical studies. In clinic, it is believed that LE-DT will offer advantages to the patient of fewer side effects at similar doses, and possibly greater effectiveness when used at higher doses. In addition, routine premedication to prevent hypersensitivity may not be required.

This study is designed to determine the following:

• The maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of LE-DT.
• The pharmacokinetics of docetaxel following intravenous administration of LE-DT.
• Any anti-tumor effects of LE-DT.

Up to 5 dose levels have been studied.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • TGEN/Scottsdale Clinical Research Institute
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Lombardi Comprehensive Cancer Center, Georgetown University

Participation Criteria

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:

• To be included in this study, patients must meet the following criteria:
• Be ≥18 years of age.
• Have advanced (local and/or metastatic) histologically documented cancer considered unresponsive to available conventional modalities or treatments.
• Have an ECOG Performance Status of 0-2.

• Have recovered from acute toxicities of prior treatment:

  • 4 weeks must have elapsed since receiving any investigational agent.
  • 4 weeks must have elapsed since receiving any radiotherapy, or treatment with cytotoxic or biologic agents (≥6 weeks for mitomycin or nitrosoureas). Chronic treatment with non-investigational gonadotropin-releasing hormone analogs or other hormonal or supportive care is permitted.

• >6 months must have elapsed since receiving a high-dose chemotherapy regimen with stem cell support.

  • 2 weeks must have elapsed since any prior surgery or granulocyte-stimulating growth factor therapy.

  • 12 months must have elapsed since any prior treatment with docetaxel. 5. Be in adequate condition as evidenced by the following clinical laboratory values:

    • Absolute neutrophil count (ANC) ≥1,500/mm3.
    • Platelets ≥100,000/mm3.
    • Hemoglobin ≥9.0 g/dL.
    • Albumin ≥3.0 g/dL.
    • Serum creatinine ≤2.0 mg/dL.
    • Total bilirubin ≤1.5 x institutional upper limit normal (ULN).

    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase ≤2.5 x ULN.

      6. Patients (male and female) must be willing to practice an effective method of birth control during the study.

      7. Patient or legal representative must understand the investigational nature of this study and sign an Institutional Review Board (IRB)/Independent Ethics Committee approved written informed consent form prior to treatment.

Exclusion Criteria:

• Patients are excluded from this study for the following:

  1. Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
  2. Any active infection requiring parenteral or oral antibiotic treatment.
  3. Known infection with human immunodeficiency virus or hepatitis virus.
  4. Active heart disease including myocardial infarction or congestive heart failure within the previous 6 months, symptomatic coronary artery disease, or arrhythmias currently requiring medication.
  5. Known or suspected active central nervous system metastasis. (Patients stable 8 weeks after completion of treatment for central nervous system metastasis are eligible.)
  6. Impending or symptomatic spinal cord compression or carcinomatous meningitis.
  7. Having pre-existing clinically significant neuropathy (NCI CTCAE Grade ≥ 2 neuromotor or Grade ≥ 2 neurosensory) except for abnormalities due to cancer.
  8. Having failed a docetaxel-containing regimen.
  9. Having known non-controllable hypersensitivity to docetaxel or liposomes.
  10. Currently receiving any other standard or investigational treatment for cancer or any other investigational agent for any indication.
  11. Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.
  12. Female patients who are pregnant or breast-feeding.
  13. Unwilling or unable to follow protocol requirements.
  14. Any condition which, in the Investigator's opinion, deems the patient an unsuitable candidate to receive study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LE-DT	Drug: LE-DT; Intravenous infusion, Upto 5 dose levels have been studied i.e. 50, 65, 85, 110 and 132 mg/m2, Every 3 weeks; Other Names: Liposome Entrapped Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the tolerability and safety	This Phase I, open-label, dose-escalation study was designed to determine the maximum tolerated dose (MTD) of LE-DT in patients with advanced cancer. LE-DT was administered by intravenous infusion, over 1 hour, once every 21 days until occurrence of disease progression or toxicity requiring early treatment discontinuation. Dose escalation was not done until the safety and tolerability at a given dose level has been confirmed.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the pharmacokinetic and anti-tumor effect	The patients were evaluated for pharmacokinetic profile upto 48 hours post treatment after cycle 1. The anti-tumor effects were evaluated after every two cycles of treatment.	1 year

Collaborators and Investigators

• Sponsor: INSYS Therapeutics Inc
• Investigators: Principal Investigator: John L Marshall, MD, Georgetowm University Medical Center

Publications and helpful links

General Publications

• Deeken JF, Slack R, Weiss GJ, Ramanathan RK, Pishvaian MJ, Hwang J, Lewandowski K, Subramaniam D, He AR, Cotarla I, Rahman A, Marshall JL. A phase I study of liposomal-encapsulated docetaxel (LE-DT) in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. 2013 Mar;71(3):627-33. doi: 10.1007/s00280-012-2048-y. Epub 2012 Dec 30.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (ACTUAL): May 1, 2010
• Study Completion (ACTUAL): May 1, 2010

Study Registration Dates

• First Submitted: June 23, 2010
• First Submitted That Met QC Criteria: June 25, 2010
• First Posted (ESTIMATE): June 28, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 4, 2011
• Last Update Submitted That Met QC Criteria: June 30, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Cancer Patients
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: LE-DT-101