Efficacy and Safety Study of LE-DT to Treat Locally Advanced or Metastatic Pancreatic Cancer
Study Details
Study Description
Brief Summary
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 removing toxic detergent used in Taxotere, the form of LE-DT, shows reduced toxicity and comparable therapeutic efficacy in pre-clinical study. The clinical evidence obtained from the NeoPharm Phase I study shows fewer side effects and possibly administered at higher dose to induce greater effectiveness of LE-DT. In addition, docetaxel has shown positive activity of protein bound taxane therapy in treating patients with pancreatic cancer. The current Phase II study is designed to accomplish the following objectives:
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Assess the antitumor effect of 110 mg/m2 LE-DT administered intravenous (IV) every three weeks in pancreatic cancer patients with locally advanced or metastatic disease
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To evaluate the progression-free survival and overall survival
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To correlate secreted protein acid rich in cysteine expression with tumor response
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To evaluate the safety of LE-DT, in particular peripheral neuropathy, water retention as well as myelotoxicity
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To correlate pharmacogenetic variations in patients with LE-DT pharmacodynamic endpoints, including toxicities.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Liposome Entrapped Docetaxel (LE-DT)
|
Drug: Liposome Entrapped Docetaxel (LE-DT)
110 mg/m2 (IV)in vein on day 1 of each 21 day cycle , 6 cycles, until progression or unacceptable toxicity
Other Names:
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Outcome Measures
Primary Outcome Measures
- Response rate of tumor size reduction at 110 mg/m2 LE-DT dose level [1 year]
Measurable disease response will be assessed by radiographic method, CT or MRI, along with serum CA 19-9 after completed 2, 4 and 6 cycle.
Secondary Outcome Measures
- SPARC tumor expression following the treatment of LE-DT at 110 mg/m2 dose level [1 year]
SPARC tumor expression will be assessed as a potential predictor of tumor response
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient is 18 years or older, male and female.
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Patient has histopathologically confirmed diagnosis of adenocarcinoma of the pancreas. Patients with islet cell neoplasms are excluded. Biopsy sample must be available for SPARC assay.
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Patients must have clinical or radiographic evidence of locally advanced or metastatic pancreatic cancer with measurable disease.
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Male or non-pregnant and non-lactating female:
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If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test (β hCG) documented within 72 hours of the first administration of study drug.
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If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator.
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Patient can be newly-diagnosed without prior treatment or have failed initial adjuvant treatment with either gemcitabine, 5-FU or capecitabine with or without radiation therapy.
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Patient has the following blood counts at baseline:
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ANC greater than or equal to 1500 per uL
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Platelets greater than or equal to 100000 per uL
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Hgb greater than or equal to 9 g per dL
- Patient has the following blood chemistry levels at baseline:
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AST (SGOT), ALT (SGPT) less than or equal to 2.5 times of the upper limit of normal range (ULN), unless liver metastases are present, then less than or equal 5 times of the ULN is allowed
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Bilirubin less than or equal to 1.5 times of the ULN
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Serum creatinine less than or equal to 1.5 times of the ULN or calculated clearance greater than or equal to 60 mL/min for patients with serum creatinine levels above the institutional normal value.
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Patient has acceptable coagulation profile as indicated by a Prothrombin time (PT) and Partial Thromboplastin Time (PTT) within normal limits (plus or minus 15%) unless explained by the use of anticoagulants
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Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
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Patient has one or more metastatic lesions or locally advanced primary tumor measurable by CT or MRI.
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Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board-approved written informed consent form prior to receiving any study related procedure.
Exclusion Criteria:
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Patient has known brain metastases.
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Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
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Patient has known infection with HIV, hepatitis B, or hepatitis C.
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Patient has undergone major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
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Patient who have received any other treatment for pancreatic cancer including radiotherapy, chemotherapy or any investigational therapy with the exception of initial adjuvant treatment including either gemcitabine, 5-FU or capecitabine with or without radiation therapy
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Patient has a history of allergy or hypersensitivity to the study drug.
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Patient has serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the patient to receive an experimental research drug.
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Patient has pre-existing peripheral neuropathy of Grade >1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
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Patient is unwilling or unable to comply with study procedures.
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Patient is enrolled in any other clinical or investigational trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lombardi Cancer Center, Georgetown University Medical Center | Washington | District of Columbia | United States | 20007-2197 |
Sponsors and Collaborators
- INSYS Therapeutics Inc
Investigators
- Principal Investigator: John L Marshall, M.D., Lombardi Cancer Center, Georgetown University Medical center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Protocol LE-DT 202