Intraperitoneal Paclitaxel for Patients With Primary Malignant Peritoneal Mesothelioma

NCT05449366 | Completed Phase 1

• 2 other identifiers: NL78373.078.212021-003637-11
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Patients primary malignant peritoneal mesothelioma (MPM), without extra-abdominal disease, that are not eligible (or willing) to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can be included in this study. Patients will be treated with intraperitoneal (IP) chemotherapy (paclitaxel) in weekly cycles. The primary aim of this study is to determine the maximum tolerable dose (MTD) of IP monotherapy with paclitaxel for patients with MPM. The secondary aims are to assess safety and feasibility of this strategy, and to study the pharmacokinetics of paclitaxel in this setting.

Conditions

Peritoneal Malignant Mesothelioma

Keywords

Intraperitoneal chemotherapy; Paclitaxel; Systemic chemotherapy; Palliative treatment; Dose-escalation study

Outcome Measures

Primary Outcomes (1)

• The maximum tolerable dose (MTD)

  The primary endpoint of the study is to determine the maximum tolerable dose (MTD) of intraperitoneal (IP) paclitaxel monotherapy, for patients with malignant peritoneal mesothelioma (MPM) who are not eligible to undergo CRS-HIPEC.

  Week 3 (after two completed cycles of therapy, each cycle is 1 week)

Secondary Outcomes (5)

• Toxicity assessment

  Week 3 (after two completed cycles of therapy, each cycle is 1 week)

• Feasibility determined by the number of cycles given

  Week 8 (after eight completed cycles of therapy, each cycle is 1 week)

• Area Under the Curve (AUC)

  At cycle 1 and 4 (each cycle is 1 week)

• Maximum concentration (Cmax)

  At cycle 1 and 4 (each cycle is 1 week)

• Elimination half life (t1/2)

  At cycle 1 and 4 (each cycle is 1 week)

Study Arms (1)

Treatment arm

EXPERIMENTAL

According to standard of care work-up for CRS-HIPEC, patients will undergo diagnostic laparoscopy to determine the feasibility of complete cytoreduction with HIPEC. In case CRS-HIPEC is not considered feasible, a peritoneal port-a-cath (PAC) system will be placed. Through this PAC, 8-16 weekly cycles of intraperitoneal chemotherapy will be administered.

Drug: Intraperitoneal Paclitaxel Solution (Ml)

Interventions

Intraperitoneal Paclitaxel Solution (Ml) DRUG

Weekly cycles of intraperitoneal paclitaxel monotherapy

Also known as: Paclitaxel

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmed diagnosis of malignant peritoneal mesothelioma
• Patients that are not eligible (or willing) to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC)
• Age ≥ 18 years old
• Written informed consent according to the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) and national/local regulations
• Patients must be ambulatory, i.e. World Health Organization-Eastern Cooperative Oncology Group (WHO-ECOG) performance status 0 or 1
• Ability to return to the Erasmus Medical Center for adequate follow-up as required by this protocol
• Patients must have normal organ function and adequate bone marrow reserve as assessed by the following laboratory requirements; absolute neutrophil count \>1.5 \* 10\^9/l, platelet count \>100\*10\^9/l and Hemoglobin \>6.0mmol /l. Patients must have a Bilirubin \<1½ x upper limit of normal (ULN), Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 x ULN

You may not qualify if:

• Extra-abdominal disease/metastatic disease established by preoperative CT-scan of thorax-abdomen and/or PET-scan. Imaging not older than two months at time of surgery
• Medical or psychological impediment to probable compliance with the protocol
• Serious concomitant disease or active infections
• History of auto-immune disease or organ allografts, or with active or chronic infection, including HIV and viral hepatitis
• Serious intercurrent chronic or acute illness such as pulmonary (COPD or asthma) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for participation in this study
• Pregnant or lactating women; for all women of child-bearing potential a negative urine pregnancy test will be required as well as the willingness to use adequate contraception during the study until 4 weeks after finishing treatment
• Absence of assurance of compliance with the protocol
• An organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent, and preclude participation in the full protocol and follow-up

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus Medical Center

Rotterdam, South Holland, 3000 CA, Netherlands

Location

MeSH Terms

Interventions

Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator (MD PhD)

Model Details: A prospective, open-label, single-center, phase-1/2 study with a classic three-plus-three dose escalation design.

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: July 8, 2022
• Study Start: February 1, 2022
• Primary Completion: June 1, 2025
• Study Completion: August 1, 2025
• Last Updated: September 2, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)