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.

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.

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.