Trial Title:
Comparing the Safety and Efficacy of First-line Polychemotherapy and Polychemotherapy in Combination With PIPAC Sessions
NCT ID:
NCT06313801
Condition:
Gastric Cancer
Conditions: Official terms:
Stomach Neoplasms
Leucovorin
Docetaxel
Oxaliplatin
Fluorouracil
Calcium
Levoleucovorin
Conditions: Keywords:
FLOT
mFLOT
dPIPAC
PIPAC
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
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
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Docetaxel 50 mg/m2 intravenously on day 1
Arm group label:
Control group
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Oxaliplatin 85 mg/m2 on Day 1
Arm group label:
Control group
Arm group label:
Study group
Intervention type:
Drug
Intervention name:
Calcium folinate
Description:
200 mg/m2 2-hour intravenous infusion on day 1
Arm group label:
Control group
Arm group label:
Study group
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
2600 mg/m2 x intravenous infusion 24-hours (infusion of the samee of the total dose of
fluorouracil for 48 hours) on day 1.
Arm group label:
Control group
Arm group label:
Study group
Intervention type:
Procedure
Intervention name:
Diagnostic laparoscopy
Description:
Access to the abdominal cavity by Hassen (3 trocars). Carboxyperitoneum - 12 mm of water
column - stable pressure maintenance throughout the operation. Revision. Photo recording
of 4 quadrants of the abdominal cavity from the paraumbilical port. The evaluation of the
PCI index. The evaluation of other distant dissemination. Standard peritoneal lavage of
300 ml Sol. NaCl 0.9 % (37 ºС), with the exposure of 3-5 minutes (with Trendelenburg and
Fowler position alternately) and the lavage aspiration, the transfer of the lavage for
the cytological examination. Biopsy of perioneal lessions if needed.The operation is
completed as standard with the extraction of laparoports and suturing of laparoport
wounds.
Arm group label:
Control group
Arm group label:
Study group
Intervention type:
Combination Product
Intervention name:
dPIPAC ( The description of the standard diagnostic laparoscopy procedure and the session of PIPAC (dPIPAC)).
Description:
Diagnostic laparoscopy described earlier and PIPAC session. The drugs for PIPAC -
Docetaxel 50 mg/ m2 diluted with saline sodium chloride to a total volume of 200 ml. The
rate of administration is 30 ml per minute. The maximum pressure in the injector system
is 250 PSI. After the spray stage, the exposure is 30 minutes while maintaining the
declared intraperitoneal pressure. After the exposure stage, only gas is removed from the
abdominal cavity. The operation is completed as standard with the extraction of
laparoports and suturing of laparoport wounds.
Arm group label:
Study group
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.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Research Institute of Clinical Oncology "Nizhny Novgorod Regional Clinical Oncological Dispensary"
Address:
City:
Nizhny Novgorod
Zip:
603126
Country:
Russian Federation
Status:
Recruiting
Contact:
Last name:
Sergey Klimin
Phone:
+79875403280
Email:
kliminsergey7@gmail.com
Start date:
January 19, 2023
Completion date:
January 19, 2026
Lead sponsor:
Agency:
Nizhny Novgorod Regional Clinical Oncology Center
Agency class:
Other
Source:
Nizhny Novgorod Regional Clinical Oncology Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06313801