Intraperitoneal and Intravenous Paclitaxel Chemotherapy With Oral Capecitabine for Gastric Adenocarcinoma With Peritoneal Carcinomatosis
Condition: Gastric Adenocarcinoma; Gastric Cancer; Esophagogastric Junction; Peritoneal Carcinomatosis
MeSH terms: Adenocarcinoma; Carcinoma; Peritoneal Neoplasms
Intervention: Paclitaxel; Capecitabine; BardPort Titanium Implanted Port with Peritoneal Catheter
Intervention description: Paclitaxel (intraperitoneal (IP) and intravenous (IV), Day 1 of each 3-week cycle: Paclitaxel IP - Intraperitoneal paclitaxel (60 mg/m^2) will be diluted in 500 mL of 0.9% normal saline (NS), to be infused as rapidly as tolerated once per 3-week cycle on Day 1. Paclitaxel IV - Intravenous paclitaxel (80 mg/m^2) will be administered concomitantly over 3 hours, diluted in 100 to 250 ml of 0.9% NS once per 3-week cycle on Day 1.; Day 1-15 of each 3-week cycle: oral capecitabine (825 mg/m^2) to be taken twice a day starting the evening of Day 1 of each cycle until the morning of Day 15, followed by a 7-day rest period during each 3-week cycle.; After peritoneal chemo infusion port is placed (Days 1-3, as dictated by clinical status), patients will begin intraperitoneal paclitaxel and intravenous paclitaxel (Day 1) followed by oral capecitabine on the evening of Day 1 to the morning of Day 15.
Intervention MeSH terms: Paclitaxel; Capecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastroesophageal Junction (Siewert III) Adenocarcinoma; Intravenous Chemotherapy; Progression Free Survival; Peritoneal Metastasis; Intraperitoneal Chemotherapy

Summary:

      Background:

      Three-fourths of people diagnosed with gastric cancer will die from it. Researchers want to
      see if giving cancer drugs in a new way can help people live longer and delay the time it
      takes for the cancer to grow.

      Objective:

      To find a better way to treat advanced stomach cancer.

      Eligibility:

      People ages 18 and older with stomach cancer that has spread throughout their belly.

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood, urine, and heart tests

      Scans

      Cancer sample: If they do not have one, they will have a biopsy.

      Tests of performance of normal activities

      Dietary assessment

      Participants will have a laparoscopy. Small cuts are made into their abdomen. A thin camera
      with a light is inserted. Small instruments are used to take biopsies. This will be repeated
      during the study to monitor the cancer. During the first laparoscopy, a port with a catheter
      attached will be put into the abdomen.

      Participants may also have an endoscopy: A thin tube with a camera is inserted through the
      mouth and into the stomach. The tube collects samples to monitor the cancer.

      Participants will get paclitaxel every 3 weeks through the abdominal port and through a small
      plastic tube in an arm vein. They will also take capecitabine by mouth twice daily for the
      first 15 days of a 21-day cycle.

      After participants finish 3 cycles, they will have scans to see how they are doing. They may
      get another course of therapy.

      Participants will have visits every 3 weeks during treatment. Then they will have follow-up
      visits for 5 years. Then they will keep in touch with researchers for the rest of their life.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Patients must have histologically or cytologically confirmed gastric adenocarcinoma,
             including Siewert III gastroesophageal junction adenocarcinoma, confirmed by the
             National Cancer Institute (NCI) Laboratory of Pathology, and have provided a block or
             unstained slides of primary or

             metastatic tumor tissue or newly obtained fresh biopsy of a tumor lesion in case
             archival tissue sample is not available.

          2. Patients may be treatment naive or have received systemic chemotherapy prior to
             enrollment:

               -  Trastuzumab allowed as prior treatment for human epidermal growth factor receptor
                  2 (HER2)/neu over-expressing cancers as clinically indicated.

               -  Last dose of chemotherapy at least 2 weeks prior to enrollment with recovery to
                  Grade 1 from chemotherapy-related toxicities.

          3. Radiographic evidence of peritoneal carcinomatosis and/or sub-radiographic evidence of
             peritoneal carcinomatosis found at staging laparoscopy.

          4. Age >=18 years. Children under the age of 18 will not participate in this study as
             gastric cancer is rare in this population.

          5. Eastern Cooperative Oncology Group (ECOG) performance status <=1

          6. Patients must have normal organ and marrow function as defined below:

             hemoglobin >=8.0 g/dL

             absolute neutrophil count >=1,000/mcL

             platelets >=100,000/mcL

             total bilirubin <=1.5 X institutional upper limit of normal

             Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase
             (SGOT)/alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) <=2.5
             X institutional upper limit of normal

             creatinine <1.5 mg/dl

             OR

             creatinine clearance >=60 mL/min/1.73 m^2 for patients with creatinine levels above
             institutional normal.

          7. Physiologically able to undergo laparoscopy and systemic chemotherapy.

          8. Ability of subject to understand and the willingness to sign a written informed
             consent document.

          9. Previous exploratory laparotomy or laparoscopy with tissue biopsy or peritoneal lavage
             is permitted.

         10. Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study treatment. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately.

         11. Patients must be co-enrolled in protocol 13C0176 (NCT01915225) and 17C0044
             (NCT03027427) for sample collection.

         12. Human immunodeficiency virus (HIV)-positive patients may be considered for this study
             only after consultation with a National Institute of Allergy and Infectious Diseases
             (NIAID) physician.

        EXCLUSION CRITERIA:

          1. Patients who are receiving any other investigational agents.

          2. Previous cytoreductive surgery or intraperitoneal chemotherapy.

          3. Disseminated extra-peritoneal or solid organ metastases:

               -  Excludes greater omentum and ovarian metastases.

               -  Radiographic signs or clinical symptoms consistent with malignant bowel
                  obstruction.

          4. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Paclitaxel or Capecitabine or other agents used in study.

          5. Previous treatment with paclitaxel or nab-paclitaxel resulting in progression of
             disease.

          6. Existing peripheral neuropathy, Grade 3 or greater.

          7. Past medical history of dihydropyrimidine dehydrogenase deficiency.

          8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          9. Pregnant women are excluded because paclitaxel and capecitabine can cause fetal harm
             when administered to pregnant women. Because there is an unknown but potential risk
             for adverse events in nursing infants secondary to treatment of the mother with
             paclitaxel and capecitabine, breastfeeding should be discontinued if the mother is
             treated with paclitaxel and capecitabine.