Clinical trial NCT04762953: Study of Sequential Systemic Therapy + Intraperitoneal Paclitaxel in Gastric/GEJ Peritoneal Carcinomatosis
Official title: Phase II Trial of Sequential Systemic Therapy Plus Intraperitoneal Paclitaxel in Gastric/GEJ Cancer Peritoneal Carcinomatosis (STOPGAP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Peritoneal Carcinomatosis
Gastroesophageal Junction Adenocarcinoma
Keywords: Gastric Cancer
Peritoneal Carcinomatosis
Gastroesophageal Junction (GEJ) Adenocarinoma
Paclitaxel
5-FU
Fluorouracil
Leucovorin
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
First posted: 2021-02-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This clinical trial is a non-randomized, open label, single arm clinical trial.
Primary purpose: TREATMENT

Brief summary: This is a phase II clinical trial assessing the safety and efficacy of sequential systemic and intraperitoneal (IP) chemotherapy in patients with primary gastric/gastroesophageal junction cancer with cytology positive peritoneal lavage and/or peritoneal carcinomatosis.

Detailed description: Patients with histologically proven primary gastric or gastroesophageal junction (Siewert 3) adenocarcinoma with positive peritoneal cytology or peritoneal carcinomatosis detected by laparoscopy, laparotomy or imaging and without evidence of distant organ metastasis will be eligible for this study. Patients will undergo systemic therapy for 3-4 months at the discretion of the medical oncologist based on molecular makers (PD-L1, HER -2 neu, MSI). Patients without distant organ metastatic progression after completion of systemic chemotherapy, will undergo diagnostic laparoscopy and IP port placement. IP regimen will consist of IV Paclitaxel, 5- FU and Leucovorin and IP Paclitaxel. Paclitaxel 40 mg/m2 will be instilled into the peritoneal cavity through the IP port on days 1 and 8, repeated every 21 days for 3 months (3-4 cycles). Restaging imaging with CT and /or diffusion weighted MRI with contrast will be obtained 4-6 weeks after completion of IP chemotherapy. Based on response and extent of disease, patients will be triaged to one of the following treatment plans: stable disease or response and PCI \>10 - continue IP chemotherapy regimen, progression - switch to second line regimen, response with PCI ≤ 10 and complete cytoreduction is feasible - consider cytoreduction surgery (CRS) with intraperitoneal chemotherapy (IPEC).

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed primary gastric or gastroesophageal adenocarcinoma and have received a minimum of three months of first line systemic treatment without visceral metastatic progression
* Must have peritoneal cytology positive disease or peritoneal carcinomatosis detected by imaging, laparoscopy or laparotomy
* Age ≥ 18 -75 years
* Performance status: ECOG performance status ≤ 2 (Appendix A) . ECOG 2 allowed is attributed to malignancy (rather than comorbidities)
* Life expectancy of greater than 6 months
* Adequate organ and marrow function as defined below:

  1. Leukocytes: ≥ 2,000/mcL
  2. Absolute Neutrophil Count: ≥ 1,500/mcL
  3. Platelets: ≥ 80,000/mcL
  4. Total Bilirubin: within normal institutional limits
  5. AST(SGOT)/ALT(SPGT): ≤5 X institutional upper limit of normal
  6. Creatinine: \< 1.5 X institutional upper limit of normal
  7. Hemoglobin: \> 8.0 g/dL (may be transfused)
  8. Serum albumin: ≥ g/dL
* Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

* Systemic treatment for unresectable or metastatic disease for more than three months prior to enrollment
* Any evidence of distant, solid organ metastases (visceral (liver, lung, brain), bone, extra-abdominal)
* Any evidence of extensive retroperitoneal lymph node metastases not amenable to resection during gastrectomy
* Any evidence of small or large bowel obstruction with the exception of gastric outlet obstruction due to primary malignancy
* Uncontrolled intercurrent illness including, but not limited to, the following conditions:

  1. Ongoing or active infection
  2. Symptomatic congestive heart failure
  3. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event,) within 3 months before initiation of treatment
  4. Unstable angina pectoris
  5. Cardiac arrhythmia
* History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ and not treated with systemic therapy.
* Inability to comply with study and follow-up procedures as judged by the Investigator
* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.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, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Has an active infection requiring systemic therapy.
* Prior surgery that would preclude safe diagnostic laparoscopy and port placement
* Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

Primary outcomes:
measure: Participants with Progression Free Survival at 1-Year
timeFrame: 1 year
measure: Incidence of Treatment-Emergent Adverse Events [Safety]
timeFrame: From date of study treatment initiation to first date of disease progression, toxicity, delay of treatment, or withdrawal of treatment, assessed up to 12 months after the last patient is enrolled.
Secondary outcomes:
measure: Overall Survival of Participants
timeFrame: From initiation of systemic treatment to up to 12 months after last patient is enrolled or until death from any cause.
measure: Patient Reported Quality of Life Outcomes
timeFrame: From initiation of study treatment until patient is off study, assessed up to 12 months after the last patient has started treatment.
Other outcomes:
measure: Expression of Plasma and Ascites Exosomal Gene Signature (EXOSIG)
timeFrame: From date of registration to up to 12 months after last patient is enrolled.
measure: Correlation of Plasma and Ascite Exosomal Gene Signature (EXOSIG) to Treatment Response
timeFrame: From date of registration to up to 12 months after last patient is enrolled.
Locations:
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center, University of California, Irvine
state: California
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: Maheswari Senthil, MD
role: PRINCIPAL_INVESTIGATOR
References: