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Intraperitoneal and Intravenous Paclitaxel Chemotherapy With Oral Capecitabine for Gastric Adenocarcinoma With Peritoneal Carcinomatosis

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ClinicalTrials.gov Identifier: NCT04034251
Recruitment Status : Not yet recruiting
First Posted : July 26, 2019
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief 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.


Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma Gastric Cancer Esophagogastric Junction Peritoneal Carcinomatosis Drug: Paclitaxel Drug: Capecitabine Device: BardPort Titanium Implanted Port withPeritoneal Catheter Phase 2

Detailed Description:

Background:

  • An estimated 28,000 cases of gastric adenocarcinoma are diagnosed annually in the U.S.
  • Peritoneal metastasis is a common finding at diagnosis, making curative surgical resection possible in an estimated 25% of patients.
  • Systemic chemotherapy is the recommended treatment for patients with metastatic gastric cancer to the peritoneal cavity, however selective use of cytoreductive surgery and intraperitoneal chemotherapy has been associated with improved overall survival.
  • Multiple chemotherapeutic agents and delivery systems have been described for intraperitoneal therapy, but no standard regimen exists.

Objective:

-Determine the progression free survival (PFS) in patients with peritoneal metastases from gastric cancer after repeated intraperitoneal chemotherapeutic infusion (IPC) and systemic paclitaxel administration with concomitant capecitabine therapy.

Eligibility:

  • Histologically confirmed adenocarcinoma of the stomach.
  • Radiographic evidence of peritoneal carcinomatosis and/or sub-radiographic evidence of peritoneal carcinomatosis found at staging laparoscopy.
  • Medically fit for systemic chemotherapy and intraperitoneal chemotherapy.
  • Men and women agegreater than or equal to 18 years.

Design:

  • Phase II, nonrandomized, open label study.
  • Patients will enroll in two cohorts: those with prior systemic chemotherapy and those who are treatment naive.
  • Patients will undergo staging laparoscopy and placement of peritoneal access port.
  • Intraperitoneal paclitaxel (20 mg/m2 weekly), intravenous paclitaxel (80 mg/m2 weekly), and capecitabine (825 mg/m2 twice daily for 14 days of each cycle) for 12 weeks.
  • Treatment response will be assessed with imaging and laparoscopy.
  • It is expected that 16-20 patients per year for total 4 years will be enrolled. The accrual ceiling is set at 70 patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Intraperitoneal and Intravenous Paclitaxel Chemotherapy With Oral Capecitabine for Gastric Adenocarcinoma With Peritoneal Carcinomatosis
Estimated Study Start Date : September 25, 2019
Estimated Primary Completion Date : May 30, 2023
Estimated Study Completion Date : January 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1/Arm 1
IP and IV paclitaxel administration with concomitant oral capecitabine
Drug: Paclitaxel
Paclitaxel (IP and IV), Day 1 of each 3-week cycle: Paclitaxel IP -Intraperitoneal paclitaxel (20 mg /m2) will be diluted in 500 mL of 0.9% NS, to be infused as rapidly as tolerated once per 3-week cycle on Day 1. Paclitaxel IV -Intravenous paclitaxel (80 mg/m2) 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.

Drug: Capecitabine
Day 1-15 of each 3-week cycle: oral capecitabine (825 mg /m2) 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.

Device: BardPort Titanium Implanted Port withPeritoneal Catheter
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.




Primary Outcome Measures :
  1. to determine progression free survival (PFS) in patients with peritoneal metastases from gastric cancer after repeated intraperitoneal chemotherapeutic infusion (IPC) and systemic paclitaxel administration with concomitant capecitabine therapy [ Time Frame: after 1 course (3 treatment cycles; 9 weeks) ]
    to determine if the response rate (median amount of time) is better than that of the response rate based on historical controls


Secondary Outcome Measures :
  1. intra-peritoneal progression free survival (iPFS) [ Time Frame: at intra-peritoneal progression ]
    median amount of time subject survives without intraperitonealdisease progression

  2. frequency of objective histopathologic response to therapy [ Time Frame: at end of each course (3 treatment cycles; 9 weeks) ]
    graded tumor biopsy

  3. distant (extra-peritoneal) disease free survival [ Time Frame: at extra-peritoneal progression ]
    median amount of time subject survives without extraperitonealdisease progression

  4. morbidity of this treatment strategy [ Time Frame: 4 years ]
    frequency of complications and adverse events

  5. overall survival [ Time Frame: death ]
    median amount of time subject survives



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  1. Patients must have histologically or cytologically confirmed gastric adenocarcinoma, including Siewert III gastroesophageal junction adenocarcinoma, confirmed by the 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 na(SqrRoot) ve or have received systemic chemotherapy prior to enrollment:

    • Trastuzumab allowed as prior treatment for HER2/neu over-expressing cancers as clinically indicated.
    • Last dose of chemotherapy at least 4 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. 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

    AST(SGOT)/ALT(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. HIV-positive patients may be considered for this study only after consultation with a 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. Patients on therapeutic anticoagulation; Note: Prophylactic anticoagulation (i.e. intralumenal heparin) for venous or arterial access devices is allowed.
  10. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04034251


Contacts
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Contact: Maureen F Connolly (240) 858-3734 maureen.connolly@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Not yet recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jeremy L Davis, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04034251     History of Changes
Other Study ID Numbers: 190129
19-C-0129
First Posted: July 26, 2019    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: August 1, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Gastroesophageal Junction (Siewert III) Adenocarcinoma
Intravenous Chemotherapy
Progression Free Survival
Peritoneal Metastasis
Intraperitoneal Chemotherapy
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Peritoneal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Abdominal Neoplasms
Peritoneal Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Capecitabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites