Testing the Addition of Paclitaxel Administered Into the Abdominal Cavity Combined With Chemotherapy for Patients With Gastric Cancer Spread to the Abdominal Cavity (NCT07001748) — Mexico Trial Details

Condition(s) studied

Gastric AdenocarcinomaGastroesophageal Junction AdenocarcinomaPeritoneal Carcinomatosis

Investigational drug(s) / intervention(s)

Standard of Care ChemotherapyBiospecimen CollectionComputed TomographyDiagnostic LaparoscopyIntraperitoneal Port PlacementMagnetic Resonance ImagingIntraperitoneal Paclitaxel →

Standard of Care Chemotherapy: The most common regimens are FOLFOX, CAPOX, FLOT, CF, and CX. Other local institutional standard of care regimens as well as targeted agents for gastric/GEJ adenocarcinoma are allowed.

Biospecimen Collection: Plasma is to be submitted at baseline and every three months for the first year or until progression, whichever comes first. For patients who have progression, their last plasma sample should be at time of progression.

Computed Tomography: Restaging imaging with CT and/or diffusion weighted MRI with contrast will be obtained after completion of 12 weeks (+/- 2 weeks) of assigned treatment (restaging will occur at this timepoint, regardless of if the patient completed all 4 cycles or not). At this point, patients with stable disease or a response will continue assigned treatment. In the absence of radiological or clinical progression, if clinically indicated by treatment team, patients may undergo diagnostic laparoscopy to assess surgical candidacy at which time a PCI assessment and biopsies of peritoneal nodules, peritoneal lavage could be performed. Cytoreduction can be offered to patients with a PCI \< 7 and if complete cytoreduction is feasible based on treating surgeon's discretion. If deemed a candidate for surgical cytoreduction, surgery should be performed within 6 weeks of the last study treatment in both arms.

Diagnostic Laparoscopy: After induction of general anesthesia, administration of preoperative antibiotics and placement of appropriate laparoscopic ports, peritoneal lavage will be performed by instillation of 200 ml of normal saline in the left upper quadrant and allowed to dwell for 5 minutes after which it will be aspirated for cytology. Extent of peritoneal disease burden will be ascertained as per the Peritoneal Cancer Index (PCI) scoring system as outlined in Appendix V.

Intraperitoneal Port Placement: Patients assigned to Arm B will undergo placement of indwelling tunneled intraperitoneal port with Teflon cuff following Step 1 randomization and during the diagnostic laparoscopy procedure.

Magnetic Resonance Imaging: Restaging imaging with CT and/or diffusion weighted MRI with contrast will be obtained after completion of 12 weeks (+/- 2 weeks) of assigned treatment (restaging will occur at this timepoint, regardless of if the patient completed all 4 cycles or not). At this point, patients with stable disease or a response will continue assigned treatment. In the absence of radiological or clinical progression, if clinically indicated by treatment team, patients may undergo diagnostic laparoscopy to assess surgical candidacy at which time a PCI assessment and biopsies of peritoneal nodules, peritoneal lavage could be performed. Cytoreduction can be offered to patients with a PCI \< 7 and if complete cytoreduction is feasible based on treating surgeon's discretion. If deemed a candidate for surgical cytoreduction, surgery should be performed within 6 weeks of the last study treatment in both arms.

Intraperitoneal Paclitaxel: Patients on Arm B will start systemic therapy + intraperitoneal paclitaxel as early as the day after Step 1 randomization and must start within 30 calendar days (including holidays) after Step 1 randomization as per the schedule shown in the table below. Therapy will be administered on Days 1 and 8 of a 21-day cycle for 4 cycles.

Study summary

This study is being done to answer the following questions:

Can we lower the chance of your gastric cancer from growing or spreading by administering paclitaxel chemotherapy directly into your abdominal cavity in addition to chemotherapy given through a vein in your arm? Will administering paclitaxel chemotherapy directly into your abdominal cavity, in addition to chemotherapy given through a vein in your arm help you live longer? We are doing this study because we want to find out if this approach is better or worse than the usual approach for your gastric cancer. The usual approach is defined as care most people get for gastric cancer.

If you decide to take part in this study, you will first receive a surgical procedure called a diagnostic laparoscopy. This will help the study doctors learn more about your gastric cancer. Laparoscopy is a minimally invasive surgery for which you will be placed under general anesthesia. Then the surgeon will make small incisions (5mm) on your belly through which a camera and thin instruments are introduced to evaluate the abdomen. This procedure takes about 1 hour to complete. Your study group will be assigned during the surgery. The study groups are described further in the 'What are the study groups?' section below.

If you are placed into the study group 1, you will not have an intraperitoneal port (a small device which is placed under the skin and fat of your upper abdomen and a tube that is placed into the abdomen).

If you are placed into the study group 2, you will have an intraperitoneal port placed. The reason is that in addition to standard chemotherapy, which is given through a vein in your arm, this port will be used to deliver the medication paclitaxel directly inside your abdomen when you are ready to start study treatment.

It is important to know that you will not know your study group until after the surgery is over. This is because information that is learned during the surgery will help determine which study group you are put in.

Once you have fully healed from this surgery, you will start study treatment. Depending on which study group you are assigned, you will either receive a standard chemotherapy regimen (the regimen will be chosen by you and your doctor) if you are in study group 1, or paclitaxel through a tube in your belly plus chemotherapy given through a vein in your arm if you are in study group 2. All participants will get treatment for three (3) months after which you will undergo reevaluation. If the disease is under control or responding to treatment, you may continue the assigned treatment until your disease gets worse, the side effects become too severe, or you may be offered a surgical procedure to remove the cancer if the amount of disease is low and can be completely removed as determined by a surgeon.

There is a very small chance that during the laparoscopy surgical procedure, the doctor might find something called "intra-abdominal adhesions". These are areas where the stomach has healed previously and created scar tissue. If this scar tissue prevents the surgeon from being able to place a port in the correct area, you would be ineligible to receive the study treatment. If this happens, you may still receive standard of care therapy after your surgery, but you will not be able to continue on the study. If you have more questions about this, you can ask your surgeon or the study team to help.

After you finish your study treatment, your doctor or study team will watch you for side effects. They will continue to follow your condition every three (3) months during the first two (2) years, then every six (6) months until year 5. You may be reevaluated with Chest/Abdomen/Pelvis scans every three-six (3-6) months for up to five (5) years if decided by your doctor.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

STEP 0 REGISTRATION: * Patient must be at least 18 years of age * Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Patient must have histologically or cytologically confirmed microsatellite stable (MSS) or mismatch repair (MMR) protein expression proficient primary gastric or gastroesophageal adenocarcinoma (Siewert 3) with synchronous cytology positive disease (cyt+) OR peritoneal carcinomatosis detected by imaging, laparoscopy or laparotomy. Patients with microsatellite instability-high (MSI-H/dMMR) mismatch repair deficient disease are not eligible * Patient must have received a minimum of 3 months and a maximum of 6 months of first line systemic treatment * Patient must be registered to Step 0 within 4 weeks of the last dose of first line systemic therapy. Patient must not have any ongoing significant adverse events that would prohibit them from undergoing a diagnostic laparoscopy procedure followed by further systemic and intraperitoneal therapy * Patient must have no evidence of small or large bowel obstruction other than gastric outlet obstruction due to primary malignancy * Patient must have no evidence of solid organ metastases except for ovarian metastases. Baseline imaging must be done within 30 days prior to Step 0 registration * Patient must have no evidence of clinically significant radiologic peritoneal disease progression during first line systemic therapy * Patient must have no evidence of extensive retroperitoneal lymph node metastases not amenable to resection during gastrectomy * Patient must have no history of prior surgery that would preclude safe diagnostic laparoscopy and port placement * Patient must have no evidence of massive ascites on imaging or history of two therapeutic paracentesis with drainage of more than 1.0 liter of ascites each time in 30 days prior to Step 0 registration * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better * Patient must not have any uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous * Patient must not have any known contraindications or drug allergies to the protocol treatment agents: paclitaxel, 5-fluorouracil, or leucovorin * Leukocytes ≥ 2,000/uL (≤ 30 days prior to Step 0 registration) * Absolute neutrophil count (ANC) ≥ 1,500/uL (≤ 30 days prior to Step 0 registration) * Platelets ≥ 75,000/uL (≤ 30 days prior to Step 0 registration) * Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). If patient has Gilbert's syndrome, total bilirubin must be \< 2.0 mg/dL (≤ 30 days prior to Step 0 registration) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 x institutional ULN (≤ 30 days prior to Step 0 registration) * Creatinine clearance ≥ 30 mL/min (estimated using Cockcroft and Gault formula or measured) (≤ 30 days prior to Step 0 registration) * Hemoglobin ≥ 8 g/dL (≤ 30 days prior to Step 0 registration) * Serum albumin ≥ 2.5 g/dL (≤ 30 days prior to Step 0 registration) * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 0 registration are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used * All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 0 registration to rule out pregnancy * A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) * Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception (or by abstaining from sexual intercourse) for the duration of their participation in the study. Arm A patients must adhere to the contraceptive requirements outlined in the product specific package inserts while on protocol treatment. Arm B patients must continue contraceptive measures for at least 3 months after the last dose of protocol treatment. In addition, both Arm A and Arm B patients who continue with targeted agents must adhere to the contraceptive requirements outlined in the product specific package inserts while on protocol treatment * Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible STEP 1 RANDOMIZATION: * Patient must have undergone a diagnostic laparoscopy with peritoneal lavage performed and aspiration for cytology obtained * The extent of peritoneal disease burden must have been assessed during the diagnostic laparoscopy with the Peritoneal Cancer Index (PCI) available * Patient must not have extensive intraabdominal adhesions that preclude safe placement of the intraperitoneal port

Primary outcome measure(s)

Progression free survival (Phase II) — From randomization to progression or death without documentation of progression, assessed up to 5 years.
For the Phase II portion, full information is expected to occur 12 months after accrual or 38 months after study activation. This power calculation is based on a stratified log rank test and accounts for a planned interim analysis at 50% information time. At 50% information time, futility test using Wieand rule would be conducted. If the study results show promising results for the investigational arm and reject the null hypothesis at interim efficacy analysis, the study will proceed to investigate Phase III portion without having a pause in accrual before starting Phase III. Otherwise, if the study is not futile at 50% information time (HR\>1), then the study will proceed and wait for the data to reach 100% information, meaning that the study will wait until the data is mature for Phase II analysis (projected to wait 12 months after end of the accrual to collect 58 PFS events).
Overall survival (Phase III) — From randomization to the date of death, of any cause, assessed up to 5 years
For the Phase III portion, a futility interim analysis is planned at 50% information time, projected to occur 4.3 years after study activation. However, because of the potential one year pause before starting Phase III portion, the futility interim analysis may occur early. Similar to the Phase II portion, the interim analysis for futility would use the Wieand rule to make sure the investigational arm is not doing worse than the control arm. For efficacy, interim analysis would start at 30% information time and be conducted every 6 months subsequently accordingly with the DSMC monitoring schedule. Approximately 1.5 additional years after completion of accrual, the OS analysis will reach 100% information time with 105 OS events.

Trial sites (78)

Facility	City	Region	Status
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care	Irvine	California	Recruiting
Cedars-Sinai Medical Center	Los Angeles	California	Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	Recruiting
Stanford Cancer Institute Palo Alto	Palo Alto	California	Recruiting
UCHealth University of Colorado Hospital	Aurora	Colorado	Recruiting
Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut	Recruiting
Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut	Recruiting
Smilow Cancer Hospital Care Center at Greenwich	Greenwich	Connecticut	Recruiting
Smilow Cancer Hospital Care Center - Guilford	Guilford	Connecticut	Recruiting
Yale University	New Haven	Connecticut	Recruiting
Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut	Recruiting
Smilow Cancer Hospital Care Center at Long Ridge	Stamford	Connecticut	Recruiting
Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut	Recruiting
Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut	Recruiting
Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut	Recruiting
Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut	Recruiting
UF Health Cancer Institute - Gainesville	Gainesville	Florida	Recruiting
Emory University Hospital Midtown	Atlanta	Georgia	Recruiting
Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	Recruiting
Emory Saint Joseph's Hospital	Atlanta	Georgia	Recruiting
Northwestern University	Chicago	Illinois	Recruiting
University of Chicago Comprehensive Cancer Center	Chicago	Illinois	Recruiting
Northwestern Medicine Cancer Center Old Irving Park	Chicago	Illinois	Recruiting
Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois	Recruiting
Northwestern Medicine Cancer Center Delnor	Geneva	Illinois	Recruiting
Northwestern Medicine Oak Brook	Oak Brook	Illinois	Recruiting
Memorial Hospital East	Shiloh	Illinois	Recruiting
Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	Recruiting
University of Kentucky/Markey Cancer Center	Lexington	Kentucky	Recruiting
University Medical Center New Orleans	New Orleans	Louisiana	Recruiting
University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	Recruiting
University of Michigan Rogel Cancer Center	Ann Arbor	Michigan	Recruiting
Henry Ford Hospital	Detroit	Michigan	Recruiting
Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan	Recruiting
West Michigan Cancer Center	Kalamazoo	Michigan	Recruiting
Mayo Clinic in Rochester	Rochester	Minnesota	Recruiting
Siteman Cancer Center at Saint Peters Hospital	City of Saint Peters	Missouri	Recruiting
Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri	Recruiting
Washington University School of Medicine	St Louis	Missouri	Recruiting
Siteman Cancer Center-South County	St Louis	Missouri	Recruiting

+ 38 more sites — see the full list on the official registry below.

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