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

NCT ID: NCT00666991

Last Updated: 2014-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2013-05-31

Brief Summary

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.

Detailed Description

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.

Conditions

Peritoneal Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

nanoparticulate paclitaxel

Intervention Type: DRUG

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. Dosing cohorts are as follows: 50 mg/m2, 82.5 mg/m2, 125 mg/m2, 175 mg/m2, 225 mg/m2, and 275 mg/m2.

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

Group Type: EXPERIMENTAL

nanoparticulate paclitaxel

Intervention Type: DRUG

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. Dosing cohorts are as follows: 50 mg/m2, 82.5 mg/m2, 125 mg/m2, 175 mg/m2, 225 mg/m2, and 275 mg/m2.

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

Group Type: EXPERIMENTAL

nanoparticulate paclitaxel

Intervention Type: DRUG

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. Dosing cohorts are as follows: 50 mg/m2, 82.5 mg/m2, 125 mg/m2, 175 mg/m2, 225 mg/m2, and 275 mg/m2.

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

Group Type: EXPERIMENTAL

nanoparticulate paclitaxel

Intervention Type: DRUG

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. Dosing cohorts are as follows: 50 mg/m2, 82.5 mg/m2, 125 mg/m2, 175 mg/m2, 225 mg/m2, and 275 mg/m2.

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

Group Type: EXPERIMENTAL

nanoparticulate paclitaxel

Intervention Type: DRUG

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. Dosing cohorts are as follows: 50 mg/m2, 82.5 mg/m2, 125 mg/m2, 175 mg/m2, 225 mg/m2, and 275 mg/m2.

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

Group Type: EXPERIMENTAL

nanoparticulate paclitaxel

Intervention Type: DRUG

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. Dosing cohorts are as follows: 50 mg/m2, 82.5 mg/m2, 125 mg/m2, 175 mg/m2, 225 mg/m2, and 275 mg/m2.

Interventions

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. Dosing cohorts are as follows: 50 mg/m2, 82.5 mg/m2, 125 mg/m2, 175 mg/m2, 225 mg/m2, and 275 mg/m2.

Intervention Type: DRUG

Other Intervention Names

Nanotax

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Kansas Medical Center

OTHER

Sponsor Role: collaborator

Beckloff Associates, Inc.

INDUSTRY

Sponsor Role: collaborator

CritiTech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gary Johnson, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Julia Chapman, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Thomas K Schulz, M.D.

Role: PRINCIPAL_INVESTIGATOR

Cancer Center of Kansas

Kathleen Moore, MD

Role: PRINCIPAL_INVESTIGATOR

Peggy and Charles Stephenson Oklahoma Cancer Center

Locations

University of Kansas Medical Center

Kansas City, Kansas, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Peggy and Charles Stephenson Oklahoma Cancer Center

Oklahoma City, Oklahoma, United States

Countries

United States

Other Identifiers

HSC#11140

Identifier Type: -

Identifier Source: org_study_id

NCT00708864

Identifier Type: -

Identifier Source: nct_alias