Oncological Benefits of Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients With T3-4 Gastric Cancer Cyt-

NCT04595929 | Recruiting

• 1 other identifier: 1-AbOn-2020
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 1

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.

Conditions

Peritoneal Carcinomatosis; Gastric Cancer

Keywords

Gastric cancer; Aerosol Chemotherapy; Regional Chemotherapy; Peritoneal Carcinomatosis; Peritoneal washings; Intraperitoneal chemotherapy

Outcome Measures

Primary Outcomes (1)

• Comparison of Overall survival (OS) in both arms

  Overall survival (OS) where OS is defined as the time from randomization to death from any cause.

  from randomization up to 5 years

Secondary Outcomes (8)

• Comparison of Overall survival rates at 3 and 5 years in both arms

  3 and 5 years after randomization

• Comparison of progression-/disease-free survival (PFS/DFS) between arms

  from randomization up to 5 years

• Comparison of peritoneal relapse rate in both arms

  from randomization up to 5 years

• PFS/DFS rates at 2, 3 & 5 years

  2, 3 & 5 years after randomization

• Rate of surgical serious adverse events (SAEs)

  After randomization of the patient until 30 days after last study-specific treatment

Study Arms (2)

PIPAC group

EXPERIMENTAL

1. Staging laparoscopy + peritoneal lavage. 2. 4 cycles of neoadjuvant chemotherapy: FLOT = Docetaxel 50 mg/m², Oxaliplatin 85 mg/m², Leucovorin 200 mg/m², 5-FU 2600 mg/m² every 2 weeks. 3. Radical gastrectomy with D2 - lymph node dissection. 4. Intraoperative Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin 7,5 mg/m², doxorubicin 1,5 mg/m². 5. Adjuvant chemotherapy according to indications.

Procedure: Staging laparoscopy; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Procedure: Radical surgery; Procedure: PIPAC; Drug: Adjuvant chemotherapy

Control group

ACTIVE COMPARATOR

1. Staging laparoscopy + peritoneal lavage. 2. 4 cycles of neoadjuvant chemotherapy: FLOT = Docetaxel 50 mg/m², Oxaliplatin 85 mg/m², Leucovorin 200 mg/m², 5-FU 2600 mg/m² every 2 weeks. 3. Radical gastrectomy with D2 - lymph node dissection. 4. Adjuvant chemotherapy according to indications.

Procedure: Staging laparoscopy; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Procedure: Radical surgery; Drug: Adjuvant chemotherapy

Interventions

Staging laparoscopy PROCEDURE

All patients undergo staging laparoscopy and peritoneal lavage.

Control group; PIPAC group

5-Fluorouracil DRUG

Day 1 q2w: 2600 mg/m² IV over 24 hours

Also known as: 5-FU

Control group; PIPAC group

Leucovorin DRUG

Day 1 q2w: 200 mg/m² IV over 30 minutes

Also known as: Calciumfolinat

Control group; PIPAC group

Oxaliplatin DRUG

Day 1 q2w: 85 mg/m² IV over 2 hours

Control group; PIPAC group

Docetaxel DRUG

Day 1 q2w: 50 mg/m² IV over 1 hour

Control group; PIPAC group

Radical surgery PROCEDURE

Radical gastrectomy with D2 - lymph node dissection.

Control group; PIPAC group

PIPAC PROCEDURE

Intraoperative Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin 7,5 mg/m², doxorubicin 1,5 mg/m².

PIPAC group

Adjuvant chemotherapy DRUG

Adjuvant chemotherapy according to indications.

Control group; PIPAC group

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• Patient pregnant or breast feeding, or planning to become pregnant.
• Any other concurrent antineoplastic treatment including irradiation.

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197101, Russia

RECRUITING

MeSH Terms

Conditions

Peritoneal Neoplasms; Stomach Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Docetaxel; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Alexander Zakharenko, PhD

  First Pavlov State Medical University of St. Petersburg

  PRINCIPAL INVESTIGATOR

• Ilya Vervekin

  First Pavlov State Medical University of St. Petersburg

  STUDY CHAIR

Central Study Contacts

Alexander Zakharenko, PhD

CONTACT

9219516183; 9516183@mail.ru

Michael Belyaev, PhD

CONTACT

89218628926; 8628926@mail.ru

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2020
• First Posted: October 22, 2020
• Study Start: February 10, 2020
• Primary Completion: October 10, 2021
• Study Completion (Estimated): January 10, 2029
• Last Updated: November 25, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)