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

A Phase 1 Study of Intraperitoneal Nanoparticle Paclitaxel in Patients With Peritoneal Malignancies

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.

Study Overview

• Status: Completed
• Conditions: Peritoneal Neoplasms
• Intervention / Treatment: Drug: nanoparticulate paclitaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Peggy and Charles Stephenson Oklahoma Cancer 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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

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. 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.; Other Names: Nanotax
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. 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.; Other Names: Nanotax
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. 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.; Other Names: Nanotax
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. 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.; Other Names: Nanotax
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. 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.; Other Names: Nanotax
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. 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.; Other Names: Nanotax

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: CritiTech, Inc.
• Collaborators: University of Kansas Medical Center; Beckloff Associates, Inc.
• Investigators: Principal Investigator: Gary Johnson, M.D., University of Kansas Medical Center; Principal Investigator: Julia Chapman, M.D., University of Kansas Medical Center; Principal Investigator: Thomas K Schulz, M.D., Cancer Center of Kansas; Principal Investigator: Kathleen Moore, MD, Peggy and Charles Stephenson Oklahoma Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: April 23, 2008
• First Submitted That Met QC Criteria: April 23, 2008
• First Posted (Estimate): April 25, 2008

Study Record Updates

• Last Update Posted (Estimate): February 27, 2014
• Last Update Submitted That Met QC Criteria: February 26, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: colon cancer; ovarian cancer; pancreatic cancer; Mullerian tumors; peritoneal cavity carcinoma; gastrointestinal tract tumor; GI tract tumor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Peritoneal Diseases; Digestive System Neoplasms; Abdominal Neoplasms; Peritoneal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: HSC#11140

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