Metronomic Neoadjuvant Capecitabine and Cyclophosphamide in HUGE Pseudomyxoma Peritonei Patients

NCT06800391 | Recruiting Phase 2 DMC

• 2 other identifiers: INT 135-242024-514329-42-00
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety and efficacy of neoadjuvant capecitabine and cyclophosphamide treatment in patients affected by huge Pseudomyxoma peritonei (PMP) (peritoneal cancer index \>28). Treatment consists of metronomic (low-dose medication for a prolonged time) of capecitabine plus cyclophosphamide for 6 months followed by standard of care cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The main question the trial aims to answer is which is the proportion of patients with complete cytoreduction at CRS/HIPEC after neoadjuvant metronomic approach with oral capecitabine and cyclophosphamide in patients affected by huge PMP.

Conditions

Pseudomyxoma Peritonei

Keywords

Pseudomyxoma peritonei; metronomic regimen; capecitabine; cyclophosphamide; cytoreductive surgery; HIPEC; peritoneal cancer index

Outcome Measures

Primary Outcomes (1)

• The proportion of patients with complete cytoreduction after neoadjuvant metronomic approach with oral capecitabine and cyclophosphamide in patients affected by huge PMP.

  Use of Completeness of Cytoreduction score to evaluate the radicality of Cytoreductive Surgery. Patients with a residual disease \<2.5 mm will be considered completely cytoreduced, otherwise incompletely cytoreduced. "Completeness of Cytoreduction Score" ranging from the best cc-0: no peritoneal nodule was seen, afterwards cc-1,tumor nodules persisting after cytoreduction are less than 2.5 mm in diameter, then cc-2, tumor nodules persisting after cytoreduction are between 2.5 mm and 2.5 cm in diameter to the worst cc-3, tumor nodules persisting after cytoreduction are greater than 2.5 cm

  6-8 months from the start of treatment

Secondary Outcomes (9)

• Radiological objective tumor response rate.

  Performed at baseline and 16 weeks from the start of treatment.

• Conversion rate

  6-8 months from the start of treatment

• Downsizing of the tumor measured by surgical Peritoneal Cancer index (PCI).

  Performed after 16 weeks.

• Safety and tolerability of neoadjuvant metronomic chemotherapy.

  6-8 months.

• Major complications (NCI-CTCAE v5) associated with CRS and HIPEC

  30 days after surgery.

Other Outcomes (1)

• Effect of neoadjuvant metronomic chemotherapy on the immunocompetence of tumor microenvironment

  Through the study completion, an average of 3 years

Study Arms (1)

Capecitabine and Cyclophosphamide

EXPERIMENTAL

Capecitabine (1250 mg/m2 /day) and Cyclophosphamide (50 mg/day) continuous daily dosing. Cycles are to be repeated every 28 days for a total of 6 cycles.

Combination Product: Capecitabine 1250 mg/m2 /day - Cyclophosphamide 50Mg/day

Interventions

Capecitabine 1250 mg/m2 /day - Cyclophosphamide 50Mg/day COMBINATION_PRODUCT

Capecitabine (1250 mg/m2 /day) and Cyclophosphamide (50 mg/day) continuous daily dosing. Cycles are to be repeated every 28 days for a total of 6 cycles.

Capecitabine and Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical/Histological diagnosis of pseudomyxoma peritonei (PMP);
• Peritoneal Cancer Index (PCI \>28) assessed by chest and abdominal CT scan at the staging phase;
• Age \>= 18 years and \<76 years;
• Performance Status (ECOG \<2);
• Adequate organ function including the following:
• Adequate bone marrow reserve: WBC count \>3.0x109/L, absolute neutrophyl count \>1.5x109/L, platelet count \>100x109/L, and hemoglobin \>10 g/dL;
• Hepatic: bilirubin \< 1.5 times the ULN, alkaline phosphatase, aspartate transaminase, and alanine transaminase \< 2.5 x UL;
• Renal: Creatinine clearance \>50 mL/min or serum creatinine \<1.5 x UNL;
• Patients compliance and geographic proximity that allows for adequate follow-up;
• Patients must sign an informed consent document (ICD);
• Male and female patients with reproductive potential must use an approved contraceptive method;

You may not qualify if:

• Peritoneal Cancer Index (PCI ≤28) assessed by chest and abdominal CT scan at the staging phase;
• DPD deficiency;
• Previous systemic chemotherapy and/or biological therapy;
• Administration of other experimental drugs during the study Pregnancy and breast-feeding;
• Serious or uncontrolled medical pathologies or active infections that would jeopardize the possibility of receiving the investigated treatment;
• Disorders that could influence the absorption of capecitabine (e.g. malabsorption), intestinal occlusion, Crohn's disease or ulcerative colitis;
• Psychiatric disorders, neurologic disease or other conditions that would make it impossible to comply with the protocol procedures;
• Positive anamnesis with regard to other neoplastic diseases except for the ones that have been cured for more than 5 years.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

MeSH Terms

Conditions

Pseudomyxoma Peritonei

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Adenocarcinoma, Mucinous; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Alessandra Raimondi, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandra Raimondi, MD

CONTACT

+39 02 2390 2581; alessandra.raimondi@istitutotumori.mi.it

Shigeki Kusamura, MD

CONTACT

+39 02 2390 3441; shigeki.kusamura@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Capecitabine will be taken orally at dose of 1250 mg/m2 /day (625 mg/m2 BID), continuous daily dosing. Cycles are to be repeated every 28 days for a total of 6 cycles. Cyclophosphamide 50 mg/day continuous daily dosing. Cycles are to be repeated every 28 days for a total of 6 cycles.

Study Record Dates

• First Submitted: November 25, 2024
• First Posted: January 30, 2025
• Study Start: November 22, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029
• Last Updated: January 30, 2025

Record last verified: 2024-12

Locations

IT (1)