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

This study has been completed.
Sponsor:
Collaborators:
University of Kansas Medical Center Research Institute, Inc.
Beckloff Associates, Inc.
Information provided by (Responsible Party):
CritiTech, Inc.
ClinicalTrials.gov Identifier:
NCT00666991
First received: April 23, 2008
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Peritoneal Neoplasms
Drug: nanoparticulate paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Intraperitoneal Nanoparticle Paclitaxel in Patients With Peritoneal Malignancies

Resource links provided by NLM:


Further study details as provided by CritiTech, Inc.:

Primary Outcome Measures:
  • Determine maximum tolerated dose and to assess qualitative and quantitative toxicities [ Time Frame: Through last patient visit ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine preliminary anti-tumor activity using RECIST criteria [ Time Frame: Through last patient visit ] [ Designated as safety issue: No ]
  • Determine pharmacokinetics of intraperitoneal administration [ Time Frame: Up to 14 days following Cycles 1 and 2 ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: July 2008
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Nanotax

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00666991

Locations
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Cancer Center of Kansas
Wichita, Kansas, United States, 67208
United States, Oklahoma
Peggy and Charles Stephenson Oklahoma Cancer Center
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
CritiTech, Inc.
University of Kansas Medical Center Research Institute, Inc.
Beckloff Associates, Inc.
Investigators
Principal Investigator: Gary Johnson, M.D. University of Kansas
Principal Investigator: Julia Chapman, M.D. University of Kansas
Principal Investigator: Thomas K Schulz, M.D. Cancer Center of Kansas
Principal Investigator: Kathleen Moore, MD Peggy and Charles Stephenson Oklahoma Cancer Center
  More Information

No publications provided

Responsible Party: CritiTech, Inc.
ClinicalTrials.gov Identifier: NCT00666991     History of Changes
Obsolete Identifiers: NCT00708864
Other Study ID Numbers: HSC#11140
Study First Received: April 23, 2008
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by CritiTech, Inc.:
ovarian cancer
Mullerian tumors
peritoneal cavity carcinoma
gastrointestinal tract tumor
GI tract tumor
pancreatic cancer
colon cancer

Additional relevant MeSH terms:
Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014