A Trial to Determine the Maximum Tolerated Dose and Evaluate the Safety and Pharmacokinetics of Docetaxel-PNP, Polymeric Nanoparticle Formulation of Docetaxel, in Subjects With Advanced Solid Malignancies

This is a phase I trial to determine the maximum tolerated dose and recommended phase II dose of docetaxel-PNP (polymeric nanoparticle formulation of docetaxel) and to evaluate the safety and pharmacokinetics of docetaxel-PNP in subjects with advanced solid malignancies.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Malignancies
• Intervention / Treatment: Drug: Docetaxel-PNP

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Asan Medical Center

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:

• Patient ages more than 18 years old
• Patient should voluntarily sign a written informed consent before study entry
• Patient historically or cytologically confirmed diagnosis of advanced solid tumor and patient with measurable disease or evaluable disease by RECIST criteria
• Progressive disease with development of new lesions or an increase in preexisting lesions or standard therapy in order to provide clinical benefit does not exist or is no longer effective
• Previous anti-cancer therapies must be completed before 21days of first study dose and Patient must have recovered from any previous therapy
• Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Patient has a life expectancy of at least 3 months

• Baseline studies for determining eligibility must be completed within 14 days of first study dose and patient has a adequate organ function including the following:

  • Hb ≥ 10g/dl
  • ANC ≥ 1.5 X 109/L
  • Platelet count ≥ 100 X 109/L
  • Serum total bilirubin ≤ 1.5 mg/dL
  • Serum AST and ALT ≤ 2.5 X UNL
  • Serum ALP ≤ 2.5ⅹUNL
  • Serum creatinine ≤ 1.5 X UNL

Exclusion Criteria:

• Patient has had a major surgery except tumor ablation within 2 weeks before screening visit
• Patient has a brain metastasis with neurologic symptom
• Patient has a sensory neuropathy or motor neuropathy ≥ grade 2 by NCI-CTCAE
• Patient has any serious concurrent disease such as:

Any medical or psychiatric condition that, in the opinion of the investigator, would prohibit the understanding and giving of informed consent Severe cardiovascular disease (e.g. ischemic heart disease requiring medication or myocardial infraction within the past six months, grade 3-4 congestive heart failure defined by the New York Heart Association criteria) Active un controlled infection.

• Patient has hypersensitivity to the Investigational product or their excipients
• Patient has participated in any other clinical trial within 4 weeks before screening visit
• Woman is pregnant or breast feeding

• Subjects who are of childbearing potential who do not use a medically acceptable method of birth control or do not agree to continue use of this method throughout the trial (screening, treatment period, and 3 weeks from the last done). A negative pregnancy test (urine or serum) should be documented within 14 days prior to initiation of trial medication for women of childbearing potential who have not been amenorrheic for at least 12 months prior to registration into the trial or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy). Medically acceptable methods include:

  • Barrier method with spermicide
  • Intrauterine device
  • Complete abstinence, etc.
• Patient who has a history of resistance, intolerance, or no response to Docetaxel therapy

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Docetaxel-PNP 20mg/m2	Drug: Docetaxel-PNP; Docetaxel-PNP, Polymeric Nanoparticle Formulation of Docetaxel
Experimental: Cohort 2; Docetaxel-PNP 35mg/m2	Drug: Docetaxel-PNP; Docetaxel-PNP, Polymeric Nanoparticle Formulation of Docetaxel
Experimental: Cohort 3; Docetaxel-PNP 45mg/m2	Drug: Docetaxel-PNP; Docetaxel-PNP, Polymeric Nanoparticle Formulation of Docetaxel
Experimental: Cohort 4; Docetaxel-PNP 60mg/m2	Drug: Docetaxel-PNP; Docetaxel-PNP, Polymeric Nanoparticle Formulation of Docetaxel
Experimental: Cohort 5; Docetaxel-PNP 75mg/m2	Drug: Docetaxel-PNP; Docetaxel-PNP, Polymeric Nanoparticle Formulation of Docetaxel
Experimental: Cohort 6; Docetaxel-PNP 90mg/m2	Drug: Docetaxel-PNP; Docetaxel-PNP, Polymeric Nanoparticle Formulation of Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The maximum tolerated dose (MTD) of Docetaxel-PNP	Administration of docetaxel-PNP was well tolerated up 6mg/m² every 3weeks by heavily pretreated patients.	up to 6 cycle
The recommended phase II dose of Docetaxel-PNP	Futher phase Ⅱ Trials are recommended at this dose level	up to 6 cycle

Secondary Outcome Measures

Outcome Measure	Time Frame
The Dose Limiting Toxicity (DLT)	up to 6 cycle
The pharmacokinetics of Docetaxel-PNP on Day 1 of 1st cycle (AUC, CL, T1/2, Tmax, Cmax, Vdss)	up to 6 cycle
Objective response rate	up to 6 cycle

Collaborators and Investigators

• Sponsor: Samyang Biopharmaceuticals Corporation
• Investigators: Principal Investigator: Kyung Hae Jung, Ph. D., Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: April 5, 2010
• First Submitted That Met QC Criteria: April 14, 2010
• First Posted (Estimate): April 15, 2010

Study Record Updates

• Last Update Posted (Actual): May 5, 2017
• Last Update Submitted That Met QC Criteria: May 2, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: DOPNP101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No