Docetaxel Lipid Microsphere (DT-LM) for Injection in Chemotherapy Patients

A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Docetaxel Lipid Microsphere for Injection in Cancer Patients Receiving Chemotherapy

Docetaxel Lipid Microsphere (DT-LM) is a novel proprietary delivery system of docetaxel developed by Shenyang Pharmaceutical University. In this Phase I study, the DT-LM was evaluated for the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) in patients with advance solid tumors. It was also evaluated for pharmacokinetic and anti-tumor effects of DT-LM compared to commerical docetaxel.

Study Overview

• Status: Unknown
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: DT-LM; Drug: docetaxel

Detailed Description

Docetaxel (currently marketed as Taxotere®), given by intravenous or intraperitoneal injection, has contributed significantly to the treatment of a variety of malignancies, such as ovarian, breast, gastric, and non-small-cell lung cancer (NSCLC), as well as head and neck cancer and some other cancers. In the preclinical, DT-LM showed reduced toxicity (especially myelosuppression）and comparable therapeutic efficacy. In clinic, it is believed that DT-LM will offer fewer side effects to the patient at similar doses, and possibly greater effectiveness when used at higher doses. DT-LM could not only avoid the serious hypersensitivity reactions caused by Tween 80, but also be stable, safe and convenient for clinical administration.

This study is designed to determine the following:

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

Controlled trial is also carrying out to reveal the differences in safety, pharmacokinetics and pharmacodynamics between DT-LM and Taxotere.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • Cancer Institute & Hospital, Chinese Academy of Medical Sciences
    • Contact: Yuankai Shi; Phone Number: 86-10-87788121
    • Principal Investigator: Yuankai Shi, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 18 and < 65, with ECOG performance status 0-1,and Life expectancy of more than 3 months.
2. Have advanced (local and/or metastatic) histologically documented cancer considered unresponsive to available conventional modalities or treatments.

3. 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).
   • 4 weeks must have elapsed since any prior surgery.

4. Be in adequate condition as evidenced by the following clinical laboratory values:

   • Absolute neutrophil count (ANC) ≥1,500/mm3.
   • Platelets ≥ 80,000/mm3.
   • Hemoglobin ≥ 9.0 g/dL.
   • WBC ≥ 4,000/mm3.
   • Total bilirubin ≤ 2.5 x institutional upper limit normal (ULN).
   • Transaminases AST (SGOT) and ALT (SGPT) ≤ 1.5 times ULN or ≤ 5 times ULN (liver metastasis).
   • Serum creatinine ≤ 1.2 times ULN, blood urea nitrogen≤ 1.2 times ULN.
5. both female and male patients must use adequate methods of contraception.
6. 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:

1. Intolerance to any antineoplastic agents belonging to the taxoid family.
2. having failed a docetaxel-containing regimen or Having known non-controllable hypersensitivity to docetaxel or lipid microsphere.
3. Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
4. Unstable or uncontrolled cardiac disease or hypertension.
5. With other serious internal diseases, uncontrolled infection or uncontrolled diabetes.
6. With Symptomatic brain metastasis not controlled.
7. Having pre-existing clinically significant neuropathy (NCI CTCAE Grade ≥ 2 neuromotor or Grade ≥ 2 neurosensory) except for abnormalities due to cancer.
8. Currently receiving any other standard or investigational treatment for cancer or any other investigational agent for any indication.
9. Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.
10. Female patients who are pregnant or breast-feeding.
11. Unwilling or unable to follow protocol requirements.
12. With history of serious allergic or allergy.
13. Not fit for the clinical trial judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DT-LM; Docetaxel Lipid Microsphere (DT-LM)	Drug: DT-LM; Intravenous infusion, Upto 6 dose levels have been studied i.e. 45, 60, 75, 90 105,and 120 mg/m2, Every 3 weeks.; Other Names: Docetaxel Lipid Microsphere
Active Comparator: Taxotere; Commerical Product	Drug: docetaxel; Intravenous infusion, 3 dose levels：60, 75, and 90 mg/m2, Every 3 weeks; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety and tolerability	This Phase I, open-label, control,dose-escalation study was designed to determine the maximum tolerated dose (MTD) of DT-LM in patients with advanced cancer. DT-LM 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.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pharmacokinetics of DT-LM and Taxotere: AUC and Cmax	The patients were evaluated for pharmacokinetic profile of DT-LM and Taxotere upto 48 hours post treatment after cycle 1 and cycle 2,respectively.	one year
Objective tumour response according to RECIST	The anti-tumor effects were evaluated after every two cycles of treatment.	one year

Collaborators and Investigators

• Sponsor: Shenyang Pharmaceutical University
• Investigators: Study Director: Xing Tang, Ph.D, Shenyang Pharmaceutical University

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: May 29, 2012
• First Submitted That Met QC Criteria: May 31, 2012
• First Posted (Estimate): June 5, 2012

Study Record Updates

• Last Update Posted (Estimate): September 30, 2014
• Last Update Submitted That Met QC Criteria: September 27, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Docetaxel; Neoplasms; Antineoplastic Agents; Pharmacologic Actions; Therapeutic Uses; Lipid Microsphere
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: SYPHU-DT-LM-01