Antibiotic Treatment and Long-term Outcomes of Patients With Pseudomyxoma Peritonei of Appendiceal Origin

Clinical Trial to Define the Effect of Perioperative H. Pylori Eradication With Antibiotic Treatment on Long Term Outcomes of Patients With Pseudomyxoma Peritonei of Appendiceal Origin Undergoing Cytoreductive Surgery/Hyperthermic Intraperitoneal Chemotherapy

The purpose of this study is to determine the impact of antibiotic therapy on the disease progression and overall survival of patients with Pseudomyxoma Peritonei (PMP).

Study Overview

• Status: Active, not recruiting
• Conditions: Pseudomyxoma Peritonei; Appendiceal Neoplasms
• Intervention / Treatment: Drug: PrevPac (Prevacid, Amoxicillin, Clarithromycin)

Detailed Description

Single center, open label, historical controlled, phase II study that proposes two courses of standard H. Pylori eradication antibiotic therapy can suppress carcinogenesis and improve the long-term outcomes of patients with PMP. The first course of antibiotics (PrevPac) will be administered before cytoreductive surgery and HIPEC and the second course afterwards. The historical control group will consist of all PMP patients from Mercy Medical Center's Tumor Registry who did not receive perioperative antibiotic treatment. Long-term statistical outcomes will be calculated using the Kaplan-Meier method and Cox proportional hazard ratio to compare pertinent variable. 80 subjects to be enrolled over 2 years, with a 5 year follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients must have measurable pseudomyxoma peritonei from appendiceal origin, confirmed by histology, cytology, or radiographical evidence -
• Age ≥ 21 years
• Eastern Cooperative Oncology Group (ECOG) performance status score≤2/Karnofsky performance status of (KPS) ≥ 70% (see Appendix B)
• Patients must have normal organ and marrow function as defined below:

Absolute neutrophil count (ANC) ≥1,000/mm3 Platelets ≥100,000/mm3 Hemoglobin ≥ 8.5 g/dL

Renal function:

Creatinine ≤1.5 times the upper limit of normal (ULN) or calculated creatinine clearance ≥60ml/min

Hepatic function:

Bilirubin ≤1.5 times ULN Alanine aminotransferase (ALT) ≤3 times ULN Aspartate aminotransferase (AST) ≤3 times ULN

• Ability of subject or Legally Authorized Representative (LAR) to understand and willingness to sign a written informed consent, approved by Mercy Medical Center Institutional Review Board (IRB)
• A negative pregnancy test for women of childbearing age with all reproductive organs intact

Exclusion Criteria:

• Patients receiving any other investigational agents
• Presence of other invasive malignancies or evidence of another cancer present within the last 3 years, excluding skin cancer
• history of, or known allergic reaction/hypersensitivity to PREVPAC or any component of similar chemical or biologic composition to PREVPAC
• Patients < 21 of age
• Pregnancy or lactation at the time of proposed assignment. Pregnant women are excluded from this study because PREVPAC is based on the pregnancy category for clarithromycin which is Category C agent with the potential for teratogenic or abortifacient effects. These potential risks may also apply to CRS/HIPEC.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol (e.g., unable to swallow pills)
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or giving informed consent
• Known active acute hepatitis and confirmed diagnosis of Human Immunodeficiency Virus (HIV) infection. HIV-positive patients on combination antiretroviral therapy are ineligible. These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Active systemic infection that requires use of parenteral antibiotics
• Renal insufficiency with serum creatinine level ≥1.5 times the upper limit of normal or calculated -
• Patients with concurrent severe medical problems unrelated to malignancy that will preclude compliance with the study or places at an unacceptable risk for participation in the study determinate by study investigators
• Patients to be maintained on any medication having severe interactions with PREVPAC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PrevPac; Study intervention: PrevPac (Prevacid, Amoxicillin, Clarithromycin)twice daily x 14 days for 2 courses (preoperative and post-operative). All eligible patients with a PMP diagnosis, undergoing CRS/HIPEC treatment, who consent to study participation will have a urea breath test prior to the first course of PrevPac. After surgery, when tolerated, each patient will take a second course of PrevPac. Patients will be seen for follow-up as clinically indicated until year 5.	Drug: PrevPac (Prevacid, Amoxicillin, Clarithromycin); 30mg Prevacid, 1g amoxicillin, 500mg clarithromycin administered together for oral use, twice daily for 14 days preoperatively and twice daily for 14 days at least 4 weeks postoperatively; Other Names: PREVPAC, U.S. Patent No. 5,013,743
No Intervention: PMP Historical Control; The historical control group will consist of all PMP patients who did not receive perioperative antibiotic treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Kaplan-Meier survival estimates	5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival measured by no evidence of disease progression, i.e. tumor markers within normal limits, no radiographical evidence of disease	Kaplan-Meier survival estimates	5 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance and safety of PrevPac administration	Rate of morbidity and mortality	Through 14 day treatment therapy
Analyze number of live bacteria in PMP tumor and mucin	In situ hybridization [ISH], either bright light or fluorescence in situ hybridization [FISH]	through study completion, an average of 5 years

Collaborators and Investigators

• Sponsor: Mercy Medical Center
• Investigators: Principal Investigator: Armando Sardi, M.D., Mercy Medical Center; Principal Investigator: Scott Merrell, PhD, Uniformed Sciences University, Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: March 6, 2015
• First Posted (Estimated): March 12, 2015

Study Record Updates

• Last Update Posted (Actual): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Pseudomyxoma Peritonei; Appendiceal cancer; CRS/HIPEC; PMP
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Neoplasms, Cystic, Mucinous, and Serous; Cecal Neoplasms; Cecal Diseases; Adenocarcinoma, Mucinous; Appendiceal Neoplasms; Pseudomyxoma Peritonei; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Amoxicillin; Clarithromycin; Lansoprazole
• Other Study ID Numbers: MMC-2014-53