A Randomized Phase II/III Trial of Intraperitoneal Paclitaxel Plus Systemic Treatment vs Systemic Treatment Alone in Gastric Carcinomatosis (STOPGAP II)
Study Description
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
-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
-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
