Testing the Addition of Paclitaxel Administered Into the Abdominal Cavity Combined With Chemotherapy for Patients With Gastric Cancer Spread to the Abdominal Cavity
Purpose
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.
Conditions
- Gastric Adenocarcinoma
- Gastroesophageal Junction Adenocarcinoma
- Peritoneal Carcinomatosis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
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
Study Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Step 1, Arm A (standard systemic therapy) |
Patients on Arm A will start systemic therapy with physician's choice of any standard-of-care systemic regimen for gastric/GEJ adenocarcinoma. Patients on Arm A will start systemic therapy as early as the day after Step 1 randomization and must start within 30 calendar days (including holidays) after Step 1 randomization. After 12 weeks (+/- 2 weeks) of standard of care treatment, patients will undergo a restaging assessment as outlined in Section 5.2 (restaging will occur at this timepoint, regardless of if the patient completed all 4 cycles or not). Patients who are found to have stable disease or a response may continue assigned standard of care treatment and will undergo restaging every 12 weeks (+/- 2 weeks) as outlined in Section 5.2. Treatment will continue until progression (radiographic progression or clinical progression as defined in Section 6), intolerance (unacceptable toxicity), or cytoreduction. |
|
|
Experimental Step 1, Arm B (Systemic Therapy + 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. Therapy will be administered on Days 1 and 8 of a 21-day cycle for 4 cycles. After 12 weeks (+/- 2 weeks) of study treatment, patients will undergo restaging assessments as outlined in Section 5.2 (restaging will occur at this timepoint, regardless of if the patient completed all 4 cycles or not). Patients who are found to have stable disease or a response may continue assigned protocol treatment and will undergo restaging every 12 weeks (+/- 2 weeks) as outlined in Section 5.2. Treatment will continue until progression (radiographic progression or clinical progression as defined in Section 6), intolerance (unacceptable toxicity), or cytoreduction. |
|
Recruiting Locations
Nashville, Tennessee 37232
Site Public Contact
800-811-8480
More Details
- Status
- Recruiting
- Sponsor
- ECOG-ACRIN Cancer Research Group
Study Contact
Detailed Description
PRIMARY OBJECTIVES: I. In the phase II portion, to determine the progression free survival (PFS) from randomization. II. In the phase III portion, to determine overall survival (OS) from randomization. SECONDARY OBJECTIVE: I. To compare the safety and tolerability of the intraperitoneal chemotherapy + systemic therapy regimen vs the systemic therapy alone regimen. OUTLINE: STEP 0: Patients undergo diagnostic laparoscopy within 4 weeks of study registration. STEP 1: Patients are randomized to 1 of 2 arms at the time of Step 0 diagnostic laparoscopy. ARM A: Patients receive standard of care systemic therapy per physician's choice. Patients with stable disease or a response after 12 weeks may continue to receive standard of care treatment in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study and may undergo additional diagnostic laparoscopies as clinically indicated. ARM B: Patients undergo placement of an intraperitoneal port. Patients receive leucovorin calcium intravenously (IV) over 15-30 minutes, fluorouracil IV push, paclitaxel IV over 1-2 hours and paclitaxel intraperitoneally (IP) on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease or a response after 12 weeks may continue to receive treatment in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and CT and/or MRI throughout the study and may undergo additional diagnostic laparoscopies as clinically indicated. After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for up to 5 years after Step 1 randomization.