Clinical trial NCT06313801: Comparing the Safety and Efficacy of First-line Polychemotherapy and Polychemotherapy in Combination With PIPAC Sessions
Official title: The Single-center Randomized Study "Comparison of Safety and Effectiveness of the First Line of Polychemotherapy and Polychemotherapy in Combination With PIPAC Sessions in Primary Gastric Cancer With Isolated Peritoneal Carcinomatosis.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: FLOT
mFLOT
dPIPAC
PIPAC
Lead sponsor: Nizhny Novgorod Regional Clinical Oncology Center
Sponsor class: OTHER_GOV
First posted: 2024-03-15
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In the control group, after diagnostic laparoscopy, 6 courses of PCT FLOT are carried out, examination every 3 courses with the performance of control diagnostic laparoscopy after 6 courses of PCT. In the study group, after diagnostic laparoscopy, FLOT PCT courses (1st, 3rd, 5th courses), mFLOT (2nd, 4th, 6th courses) are conducted, examination every 3 courses with dPIPAC sessions with docetaxel (excluding it from systemic administration) on the 2nd, 4th, 6th courses of PCT. In group 2, the function of control laparoscopy is performed by revision at the dPIPAC session of the 6th course of PCT. In both groups, with complete regression of foci along the peritoneum and Cy- in peritoneal lavage - dynamic observation or cytoreductive surgery, with incomplete response - dynamic observation before progression, with progression - the 2nd line of CT or optimal palliative care options.
Primary purpose: TREATMENT

Brief summary: After the initial diagnostic laparoscopy the Control group patients undergo 6 courses of polychemotherapy according to the FLOT scheme; the examination is carried out every 3 courses (after the 3rd and the 6th courses) with the control diagnostic laparoscopy after 6 courses of polychemotherapy. In the event of the complete regression of foci along the peritoneum and receiving Cy- in the peritoneal lavage, the dynamic observation or cytoreductive surgery is considered (optionally); in case of the incomplete response the dynamic observation is carried out until progression; in case of progression the 2nd line of chemotherapy or the optimal palliative care options depending on the clinical situation is considered.

After the initial diagnostic laparoscopy the Study group patients undergo courses of polychemotherapy according to the scheme FLOT (the 1st, the 3rd, the 5th courses) and mFLOT (the 2nd , the 4th, the 6th courses) in the amount of 6 (six, 3+3); the examination is carried out every 3 courses (after the 3rd and the 6th courses) with dPIPAC sessions using docetaxel (thus excluding it from the system administration) in the 2nd , the 4th, the 6th courses of polychemotherapy. Control diagnostic laparoscopy is not performed in the group No 2, its function is performed by the revision at the PIPAC session of the 6th course of polychemotherapy, which corresponds to the time interval of the Control group. In the event of the complete regression of foci along the peritoneum and receiving Cy- in the peritoneal lavage, the dynamic observation or cytoreductive surgery is considered (optionally); in case of the incomplete response the dynamic observation is carried out until progression; in case of progression the 2nd line of chemotherapy or the optimal palliative care options depending on the clinical situation is considered.

Detailed description: Signing the informed consent to participate in the study. All the patients with suspected peritoneal carcinomatosis (according to the results of radiation diagnostics, as well as confirmed peritoneal carcinomatosis by puncture biopsy or by taking ascitic fluid) undergo diagnostic laparoscopy at the first stage. In addition, screening will include all the patients with locally advanced gastric cancer undergoing laparoscopy prior to planning combination treatment. If they have foci of carcinomatosis in the peritoneum PCI up to 15 inclusive and/or Cy+ (as the only manifestation of M1), the patients of this group can be included in the study. The methodology for performing diagnostic laparoscopy is described below (excluding dPIPAC components). Note - the examination of the omental bursa as part of diagnostic laparoscopy is optional, depending on the clinical situation. Screening and examination of patients according to current clinical guidelines for nosology stomach cancer taking into account the examination criteria specified in this protocol. Performing initial diagnostic laparoscopy at the stationary stage according to the standard procedure (described above). If carcinomatosis is detected the evaluation of PCI is carried out by Sugarbaker. The patient randomization based on positive (Cy+) abdominal flushing and/or peritoneal dissemination with PCI index \<16. The randomization will be carried out using an Internet resource https://www.sealedenvelope.com. Taking into account the planned set and heterogeneity of the groups, the patients will be stratified before randomization according to the following factors: microscopic carcinomatosis of Cy+ only, macroscopic carcinomatosis PCI up to 7 inclusive, macroscopic carcinomatosis PCI from 8 to 15 inclusive; accordingly, the patients within the strata will be randomized separately.

The Control group (the group No 1). Within 1-4 weeks after the initial diagnostic laparoscopy the group No 1 patients start polychemotherapy courses according to the FLOT scheme in the amount of 6 (six); the examination is carried out every 3 courses (after the 3rd and the 6th courses) with the control diagnostic laparoscopy after 6 courses of polychemotherapy for no more than 2 weeks with no obvious signs of progression (in this case, the patient switches to the 2nd line of chemotherapy). The evaluation of the therapeutic pathomorphosis of foci in the peritoneum is carried out according to the PRGS system (Peritoneal Regression Grading Score). As the result of the treatment: in the event of the complete regression of foci along the peritoneum and receiving Cy- in the peritoneal lavage, after the completion of the planned treatment, the patients switch to the dynamic observation or cytoreductive surgery is considered within 1 month after the completion of polychemotherapy (optionally, by decision of the local council); in case of the incomplete response (due to the immeasurable characteristics of the tumor and the impossibility of evaluation by RECIST), the dynamic observation is carried out until progression; in case of progression the 2nd line of chemotherapy (the scheme at the discretion of the attending physician) or the optimal palliative care options depending on the clinical situation is considered; accordingly the patient completes the therapy proposed by the study. The response criteria are specified separately. Shifting the timing of chemotherapy up to 10 days and the timing of control examinations up to 10 days due to objective circumstances is considered acceptable within the study.

The Study group (the group No 2). Within 1-4 weeks after the initial diagnostic laparoscopy the group No 2 patients start polychemotherapy courses according to the scheme FLOT (the 1st , the 3rd, the 5th courses) and mFLOT (the 2nd, the 4th, the 6th courses) in the amount of 6 (six, 3+3); the examination is carried out every 3 courses (after the 3rd and the 6th courses) with with dPIPAC sessions using docetaxel the examination is carried out every 3 courses (after the 3rd and 6th) with the performance of dPIPAC sessions using docetaxel (thus excluding it from the system administration) in the 2nd , the 4th, the 6th courses of polychemotherapy (all the procedures are performed according to the method described in the protocol; the evaluation of the therapeutic pathomorphosis of lesions in the peritoneum is carried out according to the PRGS system (Peritoneal Regression Grading Score)). Control diagnostic laparoscopy is not performed in the group No 2, its function is performed by the revision at the PIPAC session of the 6th course of polychemotherapy, which corresponds to the time interval of the group No 1. As the result of the treatment: in the event of the complete regression of foci along the peritoneum and receiving Cy- in the peritoneal lavage, after the completion of the planned treatment, the patients switch to the dynamic observation or cytoreductive surgery is considered after the completion of polychemotherapy (optionally, by decision of the local council); in case of the incomplete response (due to the immeasurable characteristics of the tumor and the impossibility of evaluation by RECIST), the dynamic observation is carried out until progression; in case of progression the 2nd line of chemotherapy (the scheme at the discretion of the attending physician) or the optimal palliative care options depending on the clinical situation is considered; accordingly the patient completes the therapy proposed by the study. The method of performing the surgical manual is specified separately. The response criteria are specified separately. Shifting the timing of chemotherapy with dPIPAC sessions up to 10 days and the timing of control examinations up to 10 days due to objective circumstances is considered acceptable within the study.

Eligibility criteria: Inclusion Criteria:

1. Availability of signed informed voluntary consent of the patient
2. Age ≥18 years and ≤75 years
3. ECOG ≤1
4. Histological verification of gastric cancer and esophageal-gastric junction Siewert III (adenocarcinoma, ring-cell carcinoma)
5. Her2-neu negative tumor status
6. The presence of a preserved informative block of the primary tumor in the histological archive of the NOCOD (performing a biopsy and/or providing archival material - with the consent of the patient)
7. Verified gastric cancer (adenocarcinoma, ring-cell carcinoma) with the presence of M1 (with the only manifestation of M1 in the form of - Cy+ in initial peritoneal lavage and/or peritoneal dissemination PCI \<16)
8. Peritoneal adhesion index PAI \<16
9. Absence of active infectious, mental diseases, pronounced allergic conditions, as well as other concomitant pathology that may interfere with the implementation of the therapeutic and diagnostic measures provided for in the protocol
10. Adequate organ function (evaluation by laboratory parameters at screening - evaluation of hemoglobin, neutrophils, platelets, AST, ALT, total bilirubin, urea, creatinine)
11. Consent of men and women with preserved childbearing potential to use highly effective methods of contraception.

Exclusion Criteria:

1. Lack of informed voluntary consent of the patient
2. Age \<18 years and \>75 years
3. ECOG ≥2
4. Histological forms other than adenocarcinoma and ring-cell carcinoma of the stomach and esophageal-gastric junction Siewert III
5. Her2-neu positive tumor status
6. The absence of a preserved informative block of the primary tumor in the histological archive of the NOCOD
7. M1 with the exception of Cy+ in initial peritoneal lavage and/or peritoneal dissemination PCI \<16 (Distant metastases, including mts in supraclavicular, mediastinal, paraaortic (16 collector), ovarian metastases. Note - MTS in peripheral lymph nodes require a fine needle puncture with cytological examination for verification. In case of mts lesions of intracorporeal lymph nodes, the criteria of mts will be - dimensions of more than 15 mm along the short axis or mts-altered structure of the lymph node, regardless of size; PCI ≥16)
8. Peritoneal adhesion index PAI ≥16
9. Contraindications to performing diagnostic laparoscopy
10. Complicated primary tumor (bleeding, decompensated stenosis, dysphagia III-IV) if not corrected.
11. Decompensated concomitant pathology
12. Primary multiple tumors (except basal cell skin cancer and cervical cancer in situ - provided there are no signs of relapse of the disease)
13. Any specific antitumor treatment for stomach cancer and /or other malignant tumor in the anamnesis (except basal cell skin cancer and cervical cancer in situ - provided there are no signs of relapse of the disease)
14. Previous specialized treatment for stomach cancer
15. Known individual intolerance to drugs included in the protocol
16. Pregnancy, breast-feeding

Primary outcomes:
measure: The progression-free survival.
timeFrame: 3 years
measure: Complications from polychemotherapy.
timeFrame: 3 years
Secondary outcomes:
measure: The overall survival.
timeFrame: 3 years
measure: The completeness of the planned therapy.
timeFrame: 3 years
measure: Percentage of patient conversions to Су- and PCI- rate.
timeFrame: 3 years
measure: Surgical complications of operated patients
timeFrame: 3 years
measure: Аssessment of the quality of life
timeFrame: 3 years
Other outcomes:
Locations:
city: Nizhny Novgorod
country: Russian Federation
facility: Research Institute of Clinical Oncology "Nizhny Novgorod Regional Clinical Oncological Dispensary"
Study officials:
affiliation: Chief oncology specialist in the region
name: Sergey Gamayunov, DMS
role: STUDY_DIRECTOR
References: