Clinical trial NCT04595929: Oncological Benefits of Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients With T3-4 Gastric Cancer Cyt-
Official title: Single-center Randomized Study Evaluating of Oncological Benifits of Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients With Locally Advanced Gastric Cancer in Patients With Cyt-.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peritoneal Carcinomatosis
Gastric Cancer
Keywords: Gastric cancer
Aerosol Chemotherapy
Regional Chemotherapy
Peritoneal Carcinomatosis
Peritoneal washings
Intraperitoneal chemotherapy
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2020-10-22
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Stomach cancer is recognized as the third leading cause of death of cancer patients worldwide. Despite the radical treatment carried out, the progression of gastric cancer occurs in 30-40% of patients. The most common type of tumor progression of this localization is peritoneal carcinomatosis. When peritoneal carcinomatosis occurs, the median survival of patients does not exceed 3 months, the overall survival is no more than 6 months. Unfortunately, when peritoneal carcinomatosis occurs, palliative chemotherapy remains the only treatment option. The modern strategy for the prevention and treatment of peritoneal carcinomatosis is based on the concept of regional chemotherapy. The main methods of regional chemotherapy are hyperthermic intraperitoneal chemotherapy (HIPEC) and Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC). PIPAC is a new technology for delivering chemotherapy drugs to tumor nodes on the surface of the peritoneum and allows the cytostatic to be evenly distributed over the abdominal cavity, increasing the depth of its penetration into tumor nodes due to the properties of aerosol and gradients of intra-abdominal and interstitial pressure. The method has a number of advantages over the HIPEC method: a large penetration depth of drugs, low trauma, the possibility of repeated use. We offer PIPAC for patients with locally advanced gastric cancer and a high risk of developing peritoneal carcinomatosis in an adjuvant mode in addition to standard treatment to prevent the development of carcinomatosis.

Detailed description: The study is interventional: patients over 18 years of age with an established diagnosis of stomach cancer (c)T3-4N0-3M0 CYT- will be randomized into 2 groups using the envelope method. The control group will receive only neoadjuvant chemotherapy + gastrectomy/ distal subtotal resection with D2 lymph node dissection, the active comparison group - neoadjuvant chemotherapy + gastrectomy with D2 lymph node dissection + PIPAC (Cisplatin (7.5 mg / m²) + Doxirubicin 1.5 mg / m2)). Will be assessed: overall survival, median survival, disease-free survival, quality of life of patients.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed, medically operable, resectable stomach adenocarcinoma (cT3-4, any N category, M0).
* No preceding cytotoxic or targeted therapy.
* No prior partial or complete tumor resection.
* Female and male patient ≥ 18 and ≤ 75 years. Female patient with childbearing potential needs to have a negative pregnancy test within 7 days prior to study start. Males and females of reproductive potential must agree to practice highly effective contraceptive measures\* during the study. Male patients must also agree to refrain from father a child during treatment and additionally to use a condom during treatment period. Their female partner of childbearing potential must also agree to use an adequate contraceptive measure.

  \*highly effective (i.e. failure rate of \<1% per year when used consistently and correctly) methods: intravaginal and transdermal combined (estrogen and progestogen containing) hormonal contraception; injectable and implantable progestogen-only hormonal contraception; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).
* ECOG = 0-2.
* Exclusion of distant metastases by CT or MRI of abdomen, pelvis, and thorax, bone scan or MRI (if bone metastases are suspected due to clinical signs). Exclusion of the infiltration of any adjacent organs or structures by CT or MRI.
* Laparoscopic exclusion of peritoneal carcinomatosis at initial staging, before start of FLOT chemotherapy
* Adequate hematological, hepatic and renal function parameters:

Leukocytes ≥ 3000/mm³, platelets ≥ 100,000/mm³, neutrophil count (ANC) ≥1000/µL Serum creatinine ≤ 1.5 x upper limit of normal Bilirubin ≤ 1.5 x upper limit of normal, AST and ALT ≤ 3.0 x upper limit of normal, alkaline phosphatase ≤ 6 x upper limit of normal For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN; for patients receiving therapeutic anticoagulation: stable anticoagulant regimen.

* Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures.

Exclusion Criteria:

* Patient without neoadjuvant therapy or those who received a neoadjuvant therapy other than FLOT.
* Known hypersensitivity against 5-FU, leucovorin, oxaliplatin, or docetaxel.
* Other known contraindications against, 5-FU, leucovorin, oxaliplatin, or docetaxel.
* Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV.
* Clinically significant valvular defect.
* Criteria of primary unresectability, e.g.:

Radiologically documented evidence of major blood vessel invasion or invasion of adjacent organs (T4b).

Patients with involved retroperitoneal (e.g. para-aortal, paracaval or interaortocaval lymph nodes) or mesenterial lymph nodes (distant metastases!).

* Other severe internal disease or acute infection.
* Peripheral polyneuropathy ≥ NCI Grade II.
* Patient has undergone major surgery within 28 days prior to enrollment except staging laparoscopy.
* Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites.
* On-treatment participation in another interventional clinical study in the period 30 days prior to inclusion and during the study.
* Patient pregnant or breast feeding, or planning to become pregnant.
* Any other concurrent antineoplastic treatment including irradiation.

Primary outcomes:
measure: Comparison of Overall survival (OS) in both arms
timeFrame: from randomization up to 5 years
Secondary outcomes:
measure: Comparison of Overall survival rates at 3 and 5 years in both arms
timeFrame: 3 and 5 years after randomization
measure: Comparison of progression-/disease-free survival (PFS/DFS) between arms
timeFrame: from randomization up to 5 years
measure: Comparison of peritoneal relapse rate in both arms
timeFrame: from randomization up to 5 years
measure: PFS/DFS rates at 2, 3 & 5 years
timeFrame: 2, 3 & 5 years after randomization
measure: Rate of surgical serious adverse events (SAEs)
timeFrame: After randomization of the patient until 30 days after last study-specific treatment
measure: Patient reported outcomes: Quality of life EORTC QLQ C30 questionnaire
timeFrame: From date of screening until the date of first documented progression or last visit before date of death from any cause, whichever came first, assessed 8 weeks +/- 7 days until EOT, afterwards every 3 months up to 2 years after last patient in
measure: Patient reported outcomes: VAS pain assessment form
timeFrame: From date of screening until the date of first documented progression or last visit before date of death from any cause, whichever came first, assessed 8 weeks +/- 7 days until EOT, afterwards every 3 months up to 2 years after last patient in
measure: Rate of post-operative morbidity/mortality at day 30 after surgery acc. to Clavien-Dindo classification
timeFrame: at day 30 after surgery
Other outcomes:
Locations:
city: Saint-Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
affiliation: First Pavlov State Medical University of St. Petersburg
name: Alexander Zakharenko, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: First Pavlov State Medical University of St. Petersburg
name: Ilya Vervekin
role: STUDY_CHAIR
References: