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

Phase 2
Completed
Conditions
Esophagogastric Junction
Gastric Adenocarcinoma
Gastric Cancer
Peritoneal Carcinomatosis
Interventions
Device: BardPort Titanium Implanted Port with Peritoneal Catheter
Registration Number
NCT04034251
Lead Sponsor
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.

Detailed Description

Background:

* An estimated 28,000 cases of gastric adenocarcinoma are diagnosed annually in the United States (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 intraperitoneal progression free survival (iPFS) 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 age greater 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 undergo staging laparoscopy and placement of peritoneal access port.

* Intraperitoneal paclitaxel (60 mg/m\^2 weekly), intravenous paclitaxel (80 mg/m\^2 weekly), and capecitabine (825 mg/m\^2 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 74 patients.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Paclitaxel Intraperitoneal 20mg & Intravenous 80mg Every 3Weeks & Capecitabine 825mg/m^2 Twice DailyBardPort Titanium Implanted Port with Peritoneal CatheterIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Paclitaxel Intraperitoneal 60mg & Intravenous 80mg Every 3Weeks &Capecitabine 825mg/m^2 Twice DailyBardPort Titanium Implanted Port with Peritoneal CatheterIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Paclitaxel Intraperitoneal & Intravenous Every 3 Weeks & Capecitabine Twice DailyBardPort Titanium Implanted Port with Peritoneal CatheterIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Paclitaxel Intraperitoneal 20mg & Intravenous 80mg Every 3Weeks & Capecitabine 825mg/m^2 Twice DailyCapecitabineIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Paclitaxel Intraperitoneal 20mg & Intravenous 80mg Every 3Weeks & Capecitabine 825mg/m^2 Twice DailyPaclitaxelIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Paclitaxel Intraperitoneal 60mg & Intravenous 80mg Every 3Weeks &Capecitabine 825mg/m^2 Twice DailyCapecitabineIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Paclitaxel Intraperitoneal 60mg & Intravenous 80mg Every 3Weeks &Capecitabine 825mg/m^2 Twice DailyPaclitaxelIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Paclitaxel Intraperitoneal & Intravenous Every 3 Weeks & Capecitabine Twice DailyPaclitaxelIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Paclitaxel Intraperitoneal & Intravenous Every 3 Weeks & Capecitabine Twice DailyCapecitabineIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) in Participants With Peritoneal Metastases From Gastric Cancer After Repeated Intraperitoneal Chemotherapeutic Infusion (IPC) and Systemic Paclitaxel Administration With Concomitant Capecitabine TherapyFrom the first treatment to progression of disease, up to 2 years and 1 month

PFS is the amount of time a participant survives without progression of disease after treatment with peritoneal metastases from gastric cancer after repeated intraperitoneal chemotherapeutic infusion (IPC) and systemic paclitaxel administration with concomitant capecitabine therapy. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression is defined as an increase in peritoneal cancer index (PCI) score of greater than 4 points from baseline PCI, new ascites requiring repeat (more than 1) therapeutic paracentesis, malignant bowel obstruction, new intraperitoneal nodules or masses concerning for peritoneal metastasis, and decline in performance status not attributable to other medical causes.

Secondary Outcome Measures
NameTimeMethod
Intra-peritoneal Progression Free Survival (iPFS) Reported With an 80% Confidence IntervalFrom the first treatment to progression of disease, up to 2 years and 1 month

iPFS is the median amount of time a participant survives without intra-peritoneal disease progression reported with an 80% confidence interval. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression is defined as an increase in peritoneal cancer index (PCI) score of greater than 4 points from baseline PCI. New ascites requiring repeat (more than 1) therapeutic paracentesis, malignant bowel obstruction, new intraperitoneal nodules or masses concerning for peritoneal metastasis, and decline in performance status not attributable to other medical causes.

Overall Survival (OS)From first treatment until death, an average of 1.5 years

OS is the median amount of time a participant survives after treatment.

Number of Grades 3-5 Serious and/or Non-serious Adverse Events Related to the Research InterventionsDate treatment consent signed to date off study, 18 months and 8 days; and 25 months and 10 days for the first and second group, respectively.

Serious and/or non-serious adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death.

Intra-peritoneal Progression Free Survival (iPFS) Reported With an 95% Confidence IntervalFrom the first treatment to progression of disease, up to 2 years and 1 month

Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression is defined as an increase in peritoneal cancer index (PCI) score of greater than 4 points from baseline PCI. New ascites requiring repeat (more than 1) therapeutic paracentesis, malignant bowel obstruction, new intraperitoneal nodules or masses concerning for peritoneal metastasis, and decline in performance status not attributable to other medical causes.

Frequency of Objective Histopathologic Response to TherapyAt end of each course (3 treatment cycles; 9 weeks)

Participants metastatic tumors are biopsied at the end of a course of therapy and graded according to standard pathologic technique.

Number of Participants With Distant Extra-peritoneal Disease-free SurvivalFrom start of treatment to until time of extra-peritoneal progression, an average of 1 year

dDFS was determined based on identification of only distant sites of disease progression, such as lungs or intra-parenchymal liver. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression is defined as an increase in peritoneal cancer index (PCI) score of greater than 4 points from baseline PCI. New ascites requiring repeat (more than 1) therapeutic paracentesis, malignant bowel obstruction, new intraperitoneal nodules or masses concerning for peritoneal metastasis, and decline in performance status not attributable to other medical causes.

Number of Participants With Intra-peritoneal Progression Free Survival (iPFS)At extra-peritoneal progression, an average of 1 year

iPFS was determined based on identification of only intraperitoneal sites such as new, malignant ascites, peritoneal nodules, or ovarian metastases. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression is defined as an increase in peritoneal cancer index (PCI) score of greater than 4 points from baseline PCI. New ascites requiring repeat (more than 1) therapeutic paracentesis, malignant bowel obstruction, new intraperitoneal nodules or masses concerning for peritoneal metastasis, and decline in performance status not attributable to other medical causes.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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