Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in multimodal therapy for patients with oligometastatic peritoneal gastric cancer: a randomized multicenter phase III trial. PIPAC_VEROne

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliera Universitaria Integrata Verona

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

14 Dec 2022 → ongoing

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Independent Research Fund of AOUI Verona

External identifiers

EU CT number

2024-515981-14-00

EudraCT number

2021-000830-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate whether the association of PIPAC with chemotherapy compared to chemotherapy alone increases the
percentage of patients who undergo surgery with radical intent (CRS and HIPEC).
To evaluate whether the association of PIPAC with chemotherapy compared to chemotherapy alone increases the
progression-free survival (PFS).

Secondary objectives 7

1. To compare overall survival (OS) in patients receiving chemotherapy and PIPAC compared to patients treated with first-line chemotherapy alone
2. To compare disease-free survival (DFS) in patients receiving chemotherapy and PIPAC compared to patients treated with first line chemotherapy alone
3. To evaluate the degree of histological regression on peritoneal biopsies in the experimental arm
4. To evaluate the degree of regression on the surgical specimen in patients undergoing surgery with radical intent
5. To evaluate the change in quality of life before and after treatment in both groups
6. To assess safety in terms of incidence, nature and severity of adverse events and values laboratory abnormalities according to CTCAE v5 classification in the two arms
7. Cost-effectiveness evaluation

Conditions and MedDRA coding

Gastric adenocarcinoma with peritoneal metastases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age between 18-75 years
2. Primary gastric adenocarcinoma of first diagnosis not previously treated
3. Laparoscopic finding of positive peritoneal cytology and / or peritoneal localizations of disease (PCI ≤ 6), confirmed by histological examination
4. Signature of informed consent
5. ECOG PS scale 0-1
6. Patients of childbearing potential will be included in the study and monitored by serum pregnancy tests before each chemotherapy cycle and each PIPAC and at the end of treatment. Oral contraceptives will not be used due to the already high thrombotic risk related to the disease, but all other contraceptives will be used according to CTFG indications on contraception.

Exclusion criteria 17

1. Presence of extraperitoneal metastases
2. PCI> 6
3. Localization of the primary site of disease in the gastric esophagus junction of esophageal relevance (Siewert I-II)
4. Previous allergic reactions to cisplatin or doxorubicin
5. Haemorrhagic or occlusive manifestation of disease that candidates the patient for palliative surgery
6. ASA IV
7. Refusal of the patient to sign the consent
8. positive on diagnostic biopsies for EBV, MSI and HER2
9. pregnancy and breastfeeding
10. hypersensitivity to the active substances or to any of the excipients
11. liver failure (AST) / ALT> 3 times normal values, ALT> 3 times normal values, Bilirubin> 1.5 normal values)
12. Creatininemia> 1.25 mg / dL
13. • Ischemic / haemorrhagic stroke within the past 6 months • Acute myocardial infarction within the past 6 months • Moderate / severe heart failure (NYHA III-IV)
14. Leukopenia <2,000 / µl • Thrombocytopenia <100,000 / µl
15. Active hepatitis B or C
16. HIV infection
17. creatinine clearance less than 30ml / min

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Secondary Resectability Rate (%) evaluated as the % of patients in the 2 arms who will go to CRS and HIPEC compared to the total number of participants at the end of 6 or 12 cycles of chemotherapy in the Arm A and at the end of the 6 cycles of chemotherapy and the 3 PIPACs in arm B; PFS at 1 and 3 years measured as time from randomization at the first evidence of progression (peritoneal or extraperitoneal) or death of patient for any cause, whichever comes first.

Secondary endpoints 7

1. overall survival at 1 and 3 years, measured as survival time from randomization until death from any cause; this endpoint will be compared between the two treatment arms
2. DRS at 1 and 3 years measured as survival time from randomization until cancer-related death; this endpoint will be compared between the two treatment arms
3. For each patient in Arm B, starting from second cycle of PIPAC, a PRGS score will be assigned for each of the 4 biopsies performed, associated with an average PRGS score, given by the arithmetic mean of the individuals scores. In Arm A, this evaluation can only be carried out on the first occasion restaging after 3 months of treatment on biopsies performed during laparoscopy restaging or at the end of 6 months in those patients with stable disease who continued treatment chemotherapy
4. Degree of histological regression on the surgical specimen assessed using Tumor Regression Grade (TRG) sec. Mandard and compared between the two treatment arms in patients who will undergo cytoreduction and HIPEC
5. The quality of life QoL assessed using the validated EORTC QLQ C30 questionnaire, administered to the patient at the beginning of recruitment and after each treatment cycle or PIPAC and compared between the two treatment arms
6. Adverse events assessed by CTCAE v.5 after each treatment cycle and after each PIPAC and compared between the two treatment arms
7. Calculation of incremental cost-effectiveness ratios (Incremental Cost-Effectiveness Ratio= ICER) per additional resectable case and per year of life gained

Investigational products

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

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliera Universitaria Integrata Verona

Sponsor organisation

Azienda Ospedaliera Universitaria Integrata Verona

Address

Piazzale Aristide Stefani 1

City

Verona

Postcode

37126

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliera Universitaria Integrata Verona

Contact name

Francesco Casella

Public contact point

Organisation

Azienda Ospedaliera Universitaria Integrata Verona

Contact name

Francesco Casella

Locations

1 EU/EEA country · 6 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 13 files

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

Application history

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