Pharmacokinetic, Safety And Efficacy Study Of Nanoparticle Paclitaxel In Patients With Peritoneal Cancers

Study Overview

Pharmacokinetic, Safety and Efficacy Study of Nanoparticle Paclitaxel in Patients With Peritoneal Cancers

The purpose of this study is to evaluate the safety, pharmacokinetics and preliminary efficacy of an intraperitoneally administered suspension of nanoparticulate paclitaxel in patients with refractory malignancies principally confined to the peritoneal cavity.

This is an open-label, Phase 1, dose-escalation study evaluating the safety, pharmacokinetics and preliminary efficacy of an intraperitoneally administered suspension of nanoparticle paclitaxel (Nanotax) in patients with refractory malignancies principally confined to the peritoneal cavity. Nanotax will be administered via intraperitoneal infusion once every 28 days (equals one treatment cycle), continuing on this treatment schedule until disease progression or unacceptable toxicity is experienced. This study will treat one patient per predefined dose level until one patient experiences a dose limiting toxicity (DLT) or until one patient has a Grade 2 or higher non-hematological toxicity or a Grade 3 or higher hematological toxicity during the first cycle of treatment. At this time, two additional patients will be treated at this dose level. If these 2 additional patients do not experience a DLT, then the next cohort of three patients will be treated at the next highest dose level. If 2/3 or 3/3 patients experience a DLT then the next cohort of three patients is enrolled at the next lower dose level. If 1/3 of the patients experience a DLT, then the next cohort of three patients is enrolled at the same dose level. If 0/3 patients experience a DLT, then the next cohort of three patients is enrolled at the next highest dose level. If 2 (or more)/6 patients at a given level experience a DLT, then the maximum tolerated dose has been exceeded and another cohort of three patients is treated at the next lower dose level. The protocol will not treat above the highest dose level of 275 mg/m2. Adverse event data will be collected throughout the study. Peritoneal fluid and blood samples will be collected prior to Nanotax administration and up to 14 days following infusion for Cycle 1 and Cycle 2 only. Evaluation of tumor response using RECIST criteria will be conducted following each treatment cycle.

Peritoneal Neoplasms

DRUG: nanoparticulate paclitaxel

HSC#11140

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-04-23	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2014-02-26
First Submitted that Met QC Criteria 2008-04-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2014-02-27
First Posted (ESTIMATED) 2008-04-25	Results First Posted N/A	Last Verified 2014-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Nanotax, 50 mg/m2 Nanoparticulate paclitaxel (Nanotax) administered via intraperitoneal infusion at a dose of 50 mg/m2 once every 28 days until progression or unacceptable toxicity	DRUG: nanoparticulate paclitaxel This is a Phase 1, dose-escalation study with 6 cohorts of 1 - 6 patients. Patients receive Nanotax via intraperitoneal infusion once every 28 days continuing on this treatment schedule until disease progression or unacceptable toxicity is experienced. Do
EXPERIMENTAL: Nanotax, 82.5 mg/m2 Nanoparticulate paclitaxel (Nanotax) administered via intraperitoneal infusion at a dose of 82.5 mg/m2 once every 28 days until progression or unacceptable toxicity	DRUG: nanoparticulate paclitaxel This is a Phase 1, dose-escalation study with 6 cohorts of 1 - 6 patients. Patients receive Nanotax via intraperitoneal infusion once every 28 days continuing on this treatment schedule until disease progression or unacceptable toxicity is experienced. Do
EXPERIMENTAL: Nanotax, 125 mg/m2 Nanoparticulate paclitaxel (Nanotax) administered via intraperitoneal infusion at a dose of 125 mg/m2 once every 28 days until progression or unacceptable toxicity	DRUG: nanoparticulate paclitaxel This is a Phase 1, dose-escalation study with 6 cohorts of 1 - 6 patients. Patients receive Nanotax via intraperitoneal infusion once every 28 days continuing on this treatment schedule until disease progression or unacceptable toxicity is experienced. Do
EXPERIMENTAL: Nanotax, 175 mg/m2 Nanoparticulate paclitaxel (Nanotax) administered via intraperitoneal infusion at a dose of 175 mg/m2 once every 28 days until progression or unacceptable toxicity	DRUG: nanoparticulate paclitaxel This is a Phase 1, dose-escalation study with 6 cohorts of 1 - 6 patients. Patients receive Nanotax via intraperitoneal infusion once every 28 days continuing on this treatment schedule until disease progression or unacceptable toxicity is experienced. Do
EXPERIMENTAL: Nanotax, 225 mg/m2 Nanoparticulate paclitaxel (Nanotax) administered via intraperitoneal infusion at a dose of 225 mg/m2 once every 28 days until progression or unacceptable toxicity	DRUG: nanoparticulate paclitaxel This is a Phase 1, dose-escalation study with 6 cohorts of 1 - 6 patients. Patients receive Nanotax via intraperitoneal infusion once every 28 days continuing on this treatment schedule until disease progression or unacceptable toxicity is experienced. Do
EXPERIMENTAL: Nanotax 275 mg/m2 Nanoparticulate paclitaxel (Nanotax) administered via intraperitoneal infusion at a dose of 275 mg/m2 once every 28 days until progression or unacceptable toxicity	DRUG: nanoparticulate paclitaxel This is a Phase 1, dose-escalation study with 6 cohorts of 1 - 6 patients. Patients receive Nanotax via intraperitoneal infusion once every 28 days continuing on this treatment schedule until disease progression or unacceptable toxicity is experienced. Do

Primary Outcome Measures	Measure Description	Time Frame
Determine maximum tolerated dose and to assess qualitative and quantitative toxicities		Through last patient visit

Secondary Outcome Measures	Measure Description	Time Frame
Determine preliminary anti-tumor activity using RECIST criteria		Through last patient visit
Determine pharmacokinetics of intraperitoneal administration		Up to 14 days following Cycles 1 and 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients must be at least 18 years of age.
Patients must have histologic or cytologic diagnosis of carcinoma predominantly confined to the peritoneal cavity.
Patients must have failed all potentially curative therapy and have no other systemic treatment options available for extra-peritoneal disease. Patients with ovarian cancer that are platinum sensitive must have failed primary and at least one salvage regimen. Patients may undergo surgical debulking prior to entry into the trial.
At least 28 days must have elapsed since completion of any other previous chemotherapy treatment received prior to registration in this study.
Patients may have received prior abdominal surgery greater than 2 weeks prior to registration. Patients must have recovered from all effects of the surgical procedure.
Patients must have a Zubrod Performance Status of 0 - 2.
Patients must have a pretreatment granulocyte count greater than or equal to 1,500/microliter and platelet count greater than or equal to 100,000/microliter obtained within 14 days prior to registration.
Patients must have adequate renal function as documented by a serum creatinine less than or equal to 1.5 times the institutional upper limit of normal obtained within 14 days prior to registration.
Patients must have adequate hepatic function as documented by a bilirubin of less than or equal to 2 times the institutional upper limit of normal and an SGOT less than 5 times the institutional upper limit of normal obtained within 14 days prior to registration. Patients with hepatobiliary stents are eligible for this trial if the bilirubin meets the above parameter.
There should be no plans for the patient to receive concomitant radiation therapy, hormonal therapy, or other chemotherapy for their tumor while on this protocol.

Patients with active inflammatory bowel disease or chronic diarrhea
Patients with uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within previous 6 months or serious uncontrolled cardiac arrhythmia
Patients with active infection requiring systemic therapy
Pregnant or nursing women
Patients with Grade 2 or greater sensory neuropathy (by NCI Common Toxicity Criteria) at the time of study registration
Patients taking concomitant medications demonstrated to inhibit or induce CYP3A4 or CYP2C8
Patients with pre-existing conditions that prohibit the use of intravenous dexamethasone at the recommended dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

University of Kansas Medical Center
Beckloff Associates, Inc.

Investigators

PRINCIPAL_INVESTIGATOR: Gary Johnson, M.D., University of Kansas Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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