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Intraperitoneal Paclitaxel-loaded TPM for Treatment of Peritoneal Carcinomatosis

Primary Purpose

Peritoneal Carcinomatosis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Paclitaxel-loaded tumor penetrating microparticles
Sponsored by
Carlos Chan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peritoneal Carcinomatosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Ability to understand and the willingness to sign a written informed consent document
  • Have pathology proven peritoneal carcinomatosis (PC) due to colorectal, ovarian, gastric, pancreatic, appendiceal cancer or mesothelioma, or suspected peritoneal metastasis based on radiological findings. (Patient to come off study if no pathology evidence of peritoneal metastasis at the time of surgery)
  • No other standard treatment options are available
  • Measurable intraperitoneal disease by RECIST v1.1 criteria , or by radiological PCI scoring when RECIST is not feasible, on imaging studies
  • 18 to 75 years of age
  • Have an ECOG performance of 0 to 2
  • Have adequate organ and bone marrow functions as indicated by:
  • Leukocytes ≥ 3000/mcL
  • Absolute neutrophil count ≥ 1500/mcL
  • Platelets ≥ 100000/mcL
  • Total bilirubin within normal institutional limits
  • AST (SGOT) < 3 x institutional upper limit of normal
  • ALT (SPGT) < 3 x institutional upper limit of normal
  • Medically fit for surgery. Defined as: Patients who are able to undergo general anesthesia for abdominal surgery and have a metabolic equivalent (METs) ≥ 4

  • Have adequate contraception, as follows:

    1. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 10 months beyond the last dose of TPM. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
    2. A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • has not undergone a hysterectomy or bilateral oophorectomy; or

  • has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

    c. Men with partners of child bearing potential must use barrier contraceptive

    d. Men of child-bearing potential must not donate sperm while on this study and for 7 months after the last dose of TPM

Acceptable forms of birth control are listed below:

  • One Barrier method (cervical cap with spermicide plus male condom; diaphragm with spermicide plus male condom) OR
  • Hormonal method (oral contraceptives, implants, or injections) or an intrauterine device (e.g., Copper-T)

Exclusion Criteria:

  • Presence of mucinous ascites
  • Evidence of extra-peritoneal metastases
  • Current or expected use of other investigational agents
  • Received systemic chemotherapy or radiotherapy within 3 weeks prior to study enrollment or not recovering from adverse events (e.g., recovery to ≤ Grade 1)
  • Abdominal cavity deemed not accessible by treating surgeon due to prior abdominal surgery
  • History of allergic reactions to paclitaxel, PLG co-polymer, mannitol, or polysorbate 80
  • Uncontrolled intercurrent illness
  • Currently active second malignancy other than non-melanoma skin cancer
  • Pregnancy, nursing, or plans to become pregnant for the duration of study participation including 10 months beyond the last dose of TPM
  • Grade 2 or higher peripheral neuropathy
  • CrCL ≤ 4 mL/min
  • Actively treated for other malignancy
  • Patients with HIV or Hepatitis B/C requiring the use of ART agents

Sites / Locations

  • University of Iowa Hospitals & ClinicsRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intraperitoneal paclitaxel-loaded tumor penetrating microparticles (TPM)

Arm Description

Paclitaxel-loaded tumor penetrating microparticles (TPM), dose escalation starting at 50 mg/m^2 instilled in the peritoneal cavity at study start and again 6-8 weeks after the first TPM treatment.

Outcomes

Primary Outcome Measures

Assess safety of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
The incidence of treatment-emergent adverse events will be summarized by system organ class and/or preferred term, type of adverse event, severity (based on NCI CTCAE v5.0 grades), and relation to study treatment using the safety population.
Determine the maximum tolerated dose (MTD) of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
Dose escalation will proceed using an accelerated titration design (ATD). Subjects will be observed for 4 weeks after the first course of TPM treatment for any potential dose limiting toxicities (DLT). The MTD is defined as the highest dose level for which at most 1 out of 6 patients experience a DLT.

Secondary Outcome Measures

Assess potential therapeutic efficacy of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
Tumor response will be measured by RECIST v1.1 to determine potential effective doses of intraperitoneal Paclitaxel-loaded TPM.
Measure area-under-drug concentration-time curve of Paclitaxel and tumor penetrating microparticles (TPM) in blood and peritoneal fluid
Paclitaxel-loaded TPM pharmacokinetics will be described using summary statistics, such as mean and range, and graphical displays.
Measure maximum drug concentration of Paclitaxel and tumor penetrating microparticles (TPM) in blood and peritoneal fluid
Paclitaxel-loaded TPM pharmacokinetics will be described using summary statistics, such as mean and range, and graphical displays.
Assess whether Paclitaxel-loaded Tumor Penetrating Microparticles (TPM) induce immune response in the peritoneal cavity
The presence or absence of T cell infiltration in peritoneal cavity.
Assess whether intra-abdominal pressure is location-dependent
Intra-abdominal hydrostatic pressures at various intraperitoneal locations will be measured at the time of laparoscopy

Full Information

First Posted
November 8, 2021
Last Updated
June 19, 2023
Sponsor
Carlos Chan
Collaborators
Institute of Quantitative Systems Pharmacology (IQSP)
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1. Study Identification

Unique Protocol Identification Number
NCT05159050
Brief Title
Intraperitoneal Paclitaxel-loaded TPM for Treatment of Peritoneal Carcinomatosis
Official Title
Phase I Trial of Intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM) for Treatment of Peritoneal Carcinomatosis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 26, 2022 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Carlos Chan
Collaborators
Institute of Quantitative Systems Pharmacology (IQSP)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A first-in-human, unblinded, phase I trial of Paclitaxel-loaded tumor penetrating microparticles (TPM) in peritoneal carcinomatosis patients who are not eligible for standard-of-care therapeutic interventions.
Detailed Description
This is a first in human study of Paclitaxel-loaded TPM, suspended in 0.5 L of 0.1% polysorbate 80 in normal saline instilled into the peritoneal cavity. An enrolled patient will (a) undergo laparoscopy during which time the hydrostatic pressures at different locations within the peritoneal cavity are measured, pretreatment tumors are biopsied and peritoneal catheter is placed, (b) receive intraperitoneal TPM during index hospital stay, and (c) followed-up to evaluate treatment-related toxicity and response. The pharmacokinetics of TPM and paclitaxel in peritoneal fluid and systemic blood samples will be measured. Second dose of TPM is given in clinic if no disease progression or significant AEs. This is a dose escalation study. Dose escalation will proceed using an accelerated titration design (ATD) with intra-patient dose escalation. In the event either: 1 patient exhibits DLT during the first course of treatment or 2 patients exhibit grade 2 study drug-related (attribution of probable or definite) toxicity during the first course of treatment. The design switches to a standard 3+3 design at the dose that triggered the switch-two additional patients are accrued at this dose level. Decisions on when and how to escalate if the design switches to a 3+3 are described in the protocol section 6.3

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peritoneal Carcinomatosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intraperitoneal paclitaxel-loaded tumor penetrating microparticles (TPM)
Arm Type
Experimental
Arm Description
Paclitaxel-loaded tumor penetrating microparticles (TPM), dose escalation starting at 50 mg/m^2 instilled in the peritoneal cavity at study start and again 6-8 weeks after the first TPM treatment.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel-loaded tumor penetrating microparticles
Intervention Description
Paclitaxel-loaded TPM, suspended in 0.5 L of 0.1% (w/v) polysorbate 80 in 0.9% sodium chloride is instilled into the peritoneal cavity over 3 to 5 minutes. Mixing of TPM is achieved by putting patient in 5 different positions for about 80 minutes. Dose escalation, the starting dose of TPM is 50 mg/m^2 paclitaxel-equivalents. Dose escalation will follow the Accelerated Titration Design. The dose levels to which patients will be assigned in sequential cohorts are listed below. Dose escalation schedule of TPM, Dose Level 1*: 50 mg/m^2; Dose Level 2: 100 mg/m^2; Dose Level 3: 135 mg/m^2; Dose Level 4: 175 mg/m^2; Dose Level 5: 200 mg/m^2 *Starting Dose
Primary Outcome Measure Information:
Title
Assess safety of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
Description
The incidence of treatment-emergent adverse events will be summarized by system organ class and/or preferred term, type of adverse event, severity (based on NCI CTCAE v5.0 grades), and relation to study treatment using the safety population.
Time Frame
12 Weeks
Title
Determine the maximum tolerated dose (MTD) of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
Description
Dose escalation will proceed using an accelerated titration design (ATD). Subjects will be observed for 4 weeks after the first course of TPM treatment for any potential dose limiting toxicities (DLT). The MTD is defined as the highest dose level for which at most 1 out of 6 patients experience a DLT.
Time Frame
4 Weeks
Secondary Outcome Measure Information:
Title
Assess potential therapeutic efficacy of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
Description
Tumor response will be measured by RECIST v1.1 to determine potential effective doses of intraperitoneal Paclitaxel-loaded TPM.
Time Frame
12 Weeks
Title
Measure area-under-drug concentration-time curve of Paclitaxel and tumor penetrating microparticles (TPM) in blood and peritoneal fluid
Description
Paclitaxel-loaded TPM pharmacokinetics will be described using summary statistics, such as mean and range, and graphical displays.
Time Frame
8 Weeks
Title
Measure maximum drug concentration of Paclitaxel and tumor penetrating microparticles (TPM) in blood and peritoneal fluid
Description
Paclitaxel-loaded TPM pharmacokinetics will be described using summary statistics, such as mean and range, and graphical displays.
Time Frame
8 Weeks
Title
Assess whether Paclitaxel-loaded Tumor Penetrating Microparticles (TPM) induce immune response in the peritoneal cavity
Description
The presence or absence of T cell infiltration in peritoneal cavity.
Time Frame
8 Weeks
Title
Assess whether intra-abdominal pressure is location-dependent
Description
Intra-abdominal hydrostatic pressures at various intraperitoneal locations will be measured at the time of laparoscopy
Time Frame
Day 1 on study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent document Have pathology proven peritoneal carcinomatosis (PC) due to colorectal, ovarian, gastric, pancreatic, appendiceal cancer or mesothelioma, or suspected peritoneal metastasis based on radiological findings. (Patient to come off study if no pathology evidence of peritoneal metastasis at the time of surgery) No other standard treatment options are available Measurable intraperitoneal disease by RECIST v1.1 criteria , or by radiological PCI scoring when RECIST is not feasible, on imaging studies 18 to 75 years of age Have an ECOG performance of 0 to 2 Have adequate organ and bone marrow functions as indicated by: Leukocytes ≥ 3000/mcL Absolute neutrophil count ≥ 1500/mcL Platelets ≥ 100000/mcL Total bilirubin within normal institutional limits AST (SGOT) < 3 x institutional upper limit of normal ALT (SPGT) < 3 x institutional upper limit of normal Medically fit for surgery. Defined as: Patients who are able to undergo general anesthesia for abdominal surgery and have a metabolic equivalent (METs) ≥ 4 Have adequate contraception, as follows: Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 10 months beyond the last dose of TPM. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) c. Men with partners of child bearing potential must use barrier contraceptive d. Men of child-bearing potential must not donate sperm while on this study and for 7 months after the last dose of TPM Acceptable forms of birth control are listed below: One Barrier method (cervical cap with spermicide plus male condom; diaphragm with spermicide plus male condom) OR Hormonal method (oral contraceptives, implants, or injections) or an intrauterine device (e.g., Copper-T) Exclusion Criteria: Presence of mucinous ascites Evidence of extra-peritoneal metastases Current or expected use of other investigational agents Received systemic chemotherapy or radiotherapy within 3 weeks prior to study enrollment or not recovering from adverse events (e.g., recovery to ≤ Grade 1) Abdominal cavity deemed not accessible by treating surgeon due to prior abdominal surgery History of allergic reactions to paclitaxel, PLG co-polymer, mannitol, or polysorbate 80 Uncontrolled intercurrent illness Currently active second malignancy other than non-melanoma skin cancer Pregnancy, nursing, or plans to become pregnant for the duration of study participation including 10 months beyond the last dose of TPM Grade 2 or higher peripheral neuropathy CrCL ≤ 4 mL/min Actively treated for other malignancy Patients with HIV or Hepatitis B/C requiring the use of ART agents
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carlos H.F. Chan, MD, PhD
Phone
(319) 356-1727
Email
carlos-chan@uiowa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Chan, MD, PhD
Organizational Affiliation
University of Iowa
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Iowa Hospitals & Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlos H.F. Chan, MD, PhD
Phone
319-356-1727
Email
carlos-chan@uiowa.edu
First Name & Middle Initial & Last Name & Degree
Amy Kray, MA
Phone
319-356-7747
Email
amy-kray@uiowa.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Intraperitoneal Paclitaxel-loaded TPM for Treatment of Peritoneal Carcinomatosis

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