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

Primary Purpose

Peritoneal Carcinomatosis, Gastric Cancer

Status
Recruiting
Phase
Not Applicable
Locations
Russian Federation
Study Type
Interventional
Intervention
Staging laparoscopy
5-Fluorouracil
Leucovorin
Oxaliplatin
Docetaxel
Radical surgery
PIPAC
Adjuvant chemotherapy
Sponsored by
St. Petersburg State Pavlov Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peritoneal Carcinomatosis focused on measuring Gastric cancer, Aerosol Chemotherapy, Regional Chemotherapy, Peritoneal Carcinomatosis, Peritoneal washings, Intraperitoneal chemotherapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • First Pavlov State Medical University of St. PetersburgRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

PIPAC group

Control group

Arm Description

Staging laparoscopy + peritoneal lavage. 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. Radical gastrectomy with D2 - lymph node dissection. Intraoperative Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin 7,5 mg/m², doxorubicin 1,5 mg/m². Adjuvant chemotherapy according to indications.

Staging laparoscopy + peritoneal lavage. 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. Radical gastrectomy with D2 - lymph node dissection. Adjuvant chemotherapy according to indications.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Comparison of Overall survival rates at 3 and 5 years in both arms
Overall survival rates at 3 & 5 years defined as the percentage patients known to be alive after 3 and 5 years referring to the total number of patients randomized into the respective treatment arm
Comparison of progression-/disease-free survival (PFS/DFS) between arms
PFS/DFS is defined as the time from randomization to disease progression or relapse after surgery or death from any cause.
Comparison of peritoneal relapse rate in both arms
Peritoneal relapse rate defined as the percentage of patients with peritoneal relapse referring to the total number of patients randomized into the respective treatment arm
PFS/DFS rates at 2, 3 & 5 years
PFS/DFS rates at 2, 3 & 5 years defined as the percentage of patients without disease progression or relapse after surgery or death from any cause after 2, 3 and 5 years referring to the total number of patients randomized into the respective treatment arm
Rate of surgical serious adverse events (SAEs)
Rate of surgical serious adverse events, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0) grade ≥ 3 adverse events and grade ≥ 3 laboratory toxicities.
Patient reported outcomes: Quality of life EORTC QLQ C30 questionnaire
The QoL analyses will include QoL mean values, QoL response and time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment. Questionnaires given to the patients (validated quality of life questionnaires EORTC QLQ C30). EORTC QLQ C30 contains 30 questions: 28 questions regarding body fitness, daily routines, restrictions at work and hobby, appetite, fatigue, cough, breathlessness, pain, tiredness, and body conditions from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much). 2 questions regarding state of health and Quality of life with a horizontal rating from 1 to 7; 1 (very bad), 7 (excellent).
Patient reported outcomes: VAS pain assessment form
The patient´s assessment of their current level of pain on a 100-mm horizontal VAS. The left-hand extreme of the line should be described as "no pain" and the right-hand as "unbearable pain".
Rate of post-operative morbidity/mortality at day 30 after surgery acc. to Clavien-Dindo classification
Rate of post-operative morbidity/mortality will be assessed at day 30 after surgery acc. to Clavien-Dindo classification.

Full Information

First Posted
October 15, 2020
Last Updated
November 23, 2020
Sponsor
St. Petersburg State Pavlov Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT04595929
Brief Title
Oncological Benefits of Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients With T3-4 Gastric Cancer Cyt-
Acronym
GASPACCO
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

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2020 (Actual)
Primary Completion Date
October 10, 2021 (Anticipated)
Study Completion Date
January 10, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Petersburg State Pavlov Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peritoneal Carcinomatosis, Gastric Cancer
Keywords
Gastric cancer, Aerosol Chemotherapy, Regional Chemotherapy, Peritoneal Carcinomatosis, Peritoneal washings, Intraperitoneal chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
304 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PIPAC group
Arm Type
Experimental
Arm Description
Staging laparoscopy + peritoneal lavage. 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. Radical gastrectomy with D2 - lymph node dissection. Intraoperative Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin 7,5 mg/m², doxorubicin 1,5 mg/m². Adjuvant chemotherapy according to indications.
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
Staging laparoscopy + peritoneal lavage. 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. Radical gastrectomy with D2 - lymph node dissection. Adjuvant chemotherapy according to indications.
Intervention Type
Procedure
Intervention Name(s)
Staging laparoscopy
Intervention Description
All patients undergo staging laparoscopy and peritoneal lavage.
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Other Intervention Name(s)
5-FU
Intervention Description
Day 1 q2w: 2600 mg/m² IV over 24 hours
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Calciumfolinat
Intervention Description
Day 1 q2w: 200 mg/m² IV over 30 minutes
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Day 1 q2w: 85 mg/m² IV over 2 hours
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Day 1 q2w: 50 mg/m² IV over 1 hour
Intervention Type
Procedure
Intervention Name(s)
Radical surgery
Intervention Description
Radical gastrectomy with D2 - lymph node dissection.
Intervention Type
Procedure
Intervention Name(s)
PIPAC
Intervention Description
Intraoperative Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin 7,5 mg/m², doxorubicin 1,5 mg/m².
Intervention Type
Drug
Intervention Name(s)
Adjuvant chemotherapy
Intervention Description
Adjuvant chemotherapy according to indications.
Primary Outcome Measure Information:
Title
Comparison of Overall survival (OS) in both arms
Description
Overall survival (OS) where OS is defined as the time from randomization to death from any cause.
Time Frame
from randomization up to 5 years
Secondary Outcome Measure Information:
Title
Comparison of Overall survival rates at 3 and 5 years in both arms
Description
Overall survival rates at 3 & 5 years defined as the percentage patients known to be alive after 3 and 5 years referring to the total number of patients randomized into the respective treatment arm
Time Frame
3 and 5 years after randomization
Title
Comparison of progression-/disease-free survival (PFS/DFS) between arms
Description
PFS/DFS is defined as the time from randomization to disease progression or relapse after surgery or death from any cause.
Time Frame
from randomization up to 5 years
Title
Comparison of peritoneal relapse rate in both arms
Description
Peritoneal relapse rate defined as the percentage of patients with peritoneal relapse referring to the total number of patients randomized into the respective treatment arm
Time Frame
from randomization up to 5 years
Title
PFS/DFS rates at 2, 3 & 5 years
Description
PFS/DFS rates at 2, 3 & 5 years defined as the percentage of patients without disease progression or relapse after surgery or death from any cause after 2, 3 and 5 years referring to the total number of patients randomized into the respective treatment arm
Time Frame
2, 3 & 5 years after randomization
Title
Rate of surgical serious adverse events (SAEs)
Description
Rate of surgical serious adverse events, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0) grade ≥ 3 adverse events and grade ≥ 3 laboratory toxicities.
Time Frame
After randomization of the patient until 30 days after last study-specific treatment
Title
Patient reported outcomes: Quality of life EORTC QLQ C30 questionnaire
Description
The QoL analyses will include QoL mean values, QoL response and time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment. Questionnaires given to the patients (validated quality of life questionnaires EORTC QLQ C30). EORTC QLQ C30 contains 30 questions: 28 questions regarding body fitness, daily routines, restrictions at work and hobby, appetite, fatigue, cough, breathlessness, pain, tiredness, and body conditions from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much). 2 questions regarding state of health and Quality of life with a horizontal rating from 1 to 7; 1 (very bad), 7 (excellent).
Time Frame
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
Title
Patient reported outcomes: VAS pain assessment form
Description
The patient´s assessment of their current level of pain on a 100-mm horizontal VAS. The left-hand extreme of the line should be described as "no pain" and the right-hand as "unbearable pain".
Time Frame
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
Title
Rate of post-operative morbidity/mortality at day 30 after surgery acc. to Clavien-Dindo classification
Description
Rate of post-operative morbidity/mortality will be assessed at day 30 after surgery acc. to Clavien-Dindo classification.
Time Frame
at day 30 after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexander Zakharenko, PhD
Phone
9219516183
Ext
+7
Email
9516183@mail.ru
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Belyaev, PhD
Phone
89218628926
Ext
+7
Email
8628926@mail.ru
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander Zakharenko, PhD
Organizational Affiliation
First Pavlov State Medical University of St. Petersburg
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ilya Vervekin
Organizational Affiliation
First Pavlov State Medical University of St. Petersburg
Official's Role
Study Chair
Facility Information:
Facility Name
First Pavlov State Medical University of St. Petersburg
City
Saint-Petersburg
ZIP/Postal Code
197101
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ilya Vervekin
Phone
89119695285
Email
iivervekin@yandex.ru
First Name & Middle Initial & Last Name & Degree
Michael Belyaev, PhD
First Name & Middle Initial & Last Name & Degree
Alexander Zakharenko, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
No IPD will be shared.

Learn more about this trial

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

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