Metronomic neoadjuvant capecitabine and cyclophosphamide in huge (PCI>28) Pseudomyxoma peritonei (PMP) patients candidates to cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Nov 2024 → ongoing

Decision date (initial)

2024-09-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AIRC (Italian Association for Cancer Research)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

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

Secondary objectives 8

1. Radiological objective tumor response rate
2. Conversion rate
3. Downsizing of the tumor measured by surgical Peritoneal Cancer index (PCI).
4. Safety and tolerability of neoadjuvant metronomic chemotherapy.
5. Major complications (NCI-CTCAE v5) associated with CRS and HIPEC.
6. Quality of life (EORTC-QLQ-30 and EQ-5D-5L).
7. Progression-free and overall survival.
8. Effects of neoadjuvant metronomic chemotherapy on the immunocompetence of tumor microenvironment.

Conditions and MedDRA coding

Pseudomyxoma peritonei patients with high tumor burden.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Clinical/Histological diagnosis of pseudomyxoma peritonei (PMP).
2. Peritoneal Cancer Index (PCI > 28) assessed by chest and abdominal CT scan at the staging phase.
3. Age >= 18 years and <76 years
4. Performance Status (ECOG <2).
5. Adequate organ function.
6. Adequate bone marrow reserve: WBC count >3.0x10^9/L, absolute neutrophyl count >1.5x10^9/L, platelet count >100x10^9/L, and haemoglobin >10 g/d
7. Hepatic: bilirubin < 1.5 times the ULN, alkaline phosphatase, aspartate transaminase, and alanine transaminase < 2.5 xUL.
8. Renal: Creatinine clearance >50 mL/min or serum creatinine <1.5 x UNL.
9. Patients compliance and geographic proximity that allows for adequate follow-up.
10. Patients must sign an informed consent document (ICD).
11. Male and female patients with reproductive potential must use an approved contraceptive method.

Exclusion criteria 9

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. We will use Completeness of Cytoreduction to evaluate the radicality of CRS: patients with a residual disease <2.5 mm will be considered completely cytoreduced, otherwise incompletely cytoreduced,

Secondary endpoints 9

1. Objective tumor response rate will be defined by two independent radiologists by means of CT (computed tomography) scans performed at baseline, and after 16 weeks.
2. Conversion rate will be calculated dividing the number of resectable cases after the neoadjuvant chemotherapy by the number of resectable cases before neoadjuvant chemotherapy. Resectability will be evaluated with CT scans using Bouquot et al. methodology.
3. Downsizing of the tumor will be measured at the time of staging laparoscopy and CRS using Peritoneal Cancer Index (PCI).
4. Safety and tolerability objective will be measured by the incidence of adverse events (AEs), serious adverse events (SAEs), deaths, and laboratory abnormalities.
5. Major complications associated with CRS and HIPEC will be measured using NCI-CTCAE v5.
6. Quality of life will be assessed before/after neoadjuvant metronomic chemotherapy, and 30 days after the surgery with EORTC-QLQ-30 and EQ-5D-5L.
7. Progression-free Survival (PFS) is the time between the date of chemotherapy commencement and the date of Disease-Progression or Death, whichever occurs first.
8. Overall Survival (OS) is the time between the date of chemotherapy commencement and date of Death or last follow up.
9. Conduction of biological studies.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Oncologia Medica

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Public Relation Office

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications