Pressure Enabled Drug Delivery By Pancreatic Retrograde Venous Infusion For Advanced Pancreatic Carcinoma (PANC-001)

• ClinicalTrials.gov Identifier: NCT04270929
• Recruitment Status: Recruiting
• First Posted: February 17, 2020
• Last Update Posted: May 27, 2020
• Sponsor: Roger Williams Medical Center
• Collaborator: TriSalus Life Sciences
• Information provided by (Responsible Party): Ritesh Rathore, MD, Roger Williams Medical Center

Study Description

Brief Summary:

This is an open label, single institution, dose-escalation phase 1 study designed to assess the feasibility, safety, and efficacy of oxaliplatin administered via Pancreatic Retrograde Venous Infusion (PRVI) using Pressure Enabled Drug Delivery (PEDD) technology. Oxaliplatin PEDD-PRVI is administered with systemic FOLFIRI followed by FOLFIRINOX therapy for the treatment of patients with unresectable or metastatic pancreatic adenocarcinoma.

Condition or disease	Intervention/treatment	Phase
Pancreatic Adenocarcinoma	Drug: FOLFIRI; Drug: FOLFIRINOX; Device: TriSalus Infusion System	Phase 1

Detailed Description:

The treatment period consists of 6 cycles. Cycles 1 and 2 involve the regional administration of oxaliplatin via PEDD-PRVI with systemic FOLFIRI. During cycles 1 and 2, patients are evaluated on days 1, 2, 4, and 8. Cycles 3 through 6 include the systemic administration of standard of care FOLFIRINOX. During cycles 3 through 6, patients are evaluated on days 1 and 8.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is an open label, single institution, single-arm, dose-escalation phase 1 study, designed to assess the feasibility, safety, and efficacy of oxaliplatin PEDD-PRVI with systemic FOLFIRI followed by FOLFIRINOX therapy for the treatment of patients with unresectable or metastatic pancreatic adenocarcinoma
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pressure Enabled Drug Delivery By Pancreatic Retrograde Venous Infusion For Advanced Pancreatic Carcinoma
• Actual Study Start Date: December 23, 2019
• Estimated Primary Completion Date: January 1, 2021
• Estimated Study Completion Date: January 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Oxaliplatin PEDD-PRVI; Two infusions of oxaliplatin (dose escalation: 20-40 mg) over the course of 4 weeks by Pancreatic Retrograde Venous Infusion (PRVI) utilizing Pressure Enabled Drug Delivery (PEDD) technology.	Drug: FOLFIRI; During Cycles 1 and 2, standard of care systemic FOLFIRI will be delivered on Days 2-4 following oxaliplatin PEDD-PRVI.; Drug: FOLFIRINOX; During Cycles 3-6, standard of care systemic FOLFIRINOX will be administered on Days 1-3.; Device: TriSalus Infusion System; The TriSalus Infusion System administers therapeutics using PEDD technology.

Outcome Measures

Primary Outcome Measures :

1. Completion Rate of oxaliplatin PEDD-PRVI [ Time Frame: 3 months ]
   To determine the completion rate of oxaliplatin delivery by PEDD-PRVI as measured by the percentage of successful placements of the TriSalus Infusion System and delivery of the assigned dose of oxaliplatin regionally into the pancreas via RVI per each patient, at each dose-level, and across all enrolled patients in the study. Successful delivery of oxaliplatin by PEDD-PRVI will be confirmed using real-time fluoroscopic guidance. The success rate of completion of PEDD-RVI per patient and acroos all-patients will be calculated
2. Safety of oxaliplatin PEDD-PRVI: maximum tolerable dose (MTD) [ Time Frame: 3 months ]
   To determine the safety of oxaliplatin PEDD-PRVI by identifying the maximum tolerable dose (MTD).

Secondary Outcome Measures :

1. To determine local progression free survival [ Time Frame: 3 months ]
   Assess the time frame of pancreatic tumor stability prior to progression by radiographic imaging
2. To determine systemic progression free survival. [ Time Frame: 3 months ]
   Assess the time frame of metastatic tumor stability prior to progression by radiographic imaging
3. To determine overall survival [ Time Frame: 3 months ]
   As a measure of activity, overall survival will be assessed. The events for the assessment of overall survival are death events.
4. Radiographic response rates by PET [ Time Frame: 3 months ]
   Changes in tumor metabolic activity
5. Radiographic response rate by perfusion MRI [ Time Frame: 3 months ]
   Changes in tumor size
6. Serologic response rates (CA 19-9) [ Time Frame: 3 months ]
   Serial measurement of serum CA 19-9 levels

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient with histologically confirmed diagnosis of adenocarcinoma of the pancreas. Patient must have either histologic confirmation of the primary tumor or metastasis.
• Patients must have locally advanced, unresectable or metastatic pancreatic adenocarcinoma.
• Patient must be between 18 - 80 years of age.
• Patient able to understand and sign informed consent.
• Patient may be chemotherapy naïve or may have failed one line of conventional therapy

• Prior FOLFIRINOX therapy:

  • Patients who have previously received FOLFIRINOX chemotherapy for locally advanced unresectable pancreatic cancer are eligible for enrollment upon this study if they meet the following criteria-

    1. FOLFIRINOX chemotherapy was completed more than six months ago,
    2. Patients who are currently candidates for re-challenge with FOLFIRINOX chemotherapy for their recurrent cancer, and
    3. Patients have no persistent non-hematologic toxicity greater than grade 1 (due to prior FOLFIRINOX therapy)

  • Patients with metastatic cancer who are currently receiving FOLFIRINOX chemotherapy are eligible for enrollment upon this study if they meet the following criteria-

    1. Patients have received no more than six cycles of FOLFIRINOX chemotherapy,
    2. Patients have at least stable disease on imaging, and
    3. Patients have no persistent non-hematologic toxicity greater than grade 1 (due to ongoing FOLFIRINOX therapy)
• Patient with a life expectancy of greater than six months.
• Patient with performance status of 0 to 1 (ECOG).

• All patients must have adequate organ function as defined by:

  • ANC greater than or equal to 1500/mm3, platelets ≥ 100,000/mm3, Hgb ≥ to 8 g/dL; patient may be transfused to achieve Hgb ≥ 8 g/dL to satisfy enrollment criteria, or as otherwise indicated by symptoms for Hgb > 8 g/dL.
  • Creatinine ≤ 1.5mg/dl or creatinine clearance ≤ 60cc/min.
  • Direct bilirubin <1.5X ULN, alkaline phosphatase <5X ULN, and ALT/AST <5X ULN (ULN = upper limit of normal).
  • No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias, including uncontrolled atrial fibrillation/atrial flutter, evidence of prior myocardial infarction by history or EKG.
  • No serious, symptomatic obstructive or emphysematous lung disease, or asthma requiring intravenous medications within the past 12 months; no serious lung disease associated with dyspnea at normal activity levels (grade III) or at rest (grade IV), due to any cause (including cancer metastases and pleural effusions).
• Acceptable vascular anatomy as determined by CT, MR, or conventional venography.

Exclusion Criteria:

• Female patients of childbearing age will be tested for pregnancy. Pregnant and breastfeeding patients will be excluded from the study. Males who are actively seeking to have children will be made aware of the unknown risks of this study protocol on human sperm and the need to practice birth control.
• Patients with serious or unstable renal, hepatic, pulmonary, cardiovascular, endocrine, rheumatologic, or allergic disease based on history, physical exam and laboratory tests will be excluded.
• Patients with uncontrolled diabetes mellitus or a history of pancreatitis.
• Patients with cholelithiasis and a history of choledocholithiasis.
• Patients with concurrent malignancies, except for cutaneous carcinomas.
• Patients with unsuitable vascular anatomy.
• Portal vein occlusion/thrombosis, history of portal hypertension, cirrhosis, hepatitis, or with radiographic evidence of cirrhosis.

Contacts and Locations

Contacts

Contact: Enos; 4014566472; kimberly.enos@chartercare.org

Contact: Moody; 4014562268; alarkin@chartercare.org

Locations

United States, Rhode Island

Roger Williams Medical Center; Recruiting

Providence, Rhode Island, United States, 02908

Contact: Enos 401-456-6472 kimberly.enos@chartercare.org

Contact: Moody 4014562268 alarkin@chartercare.org

Principal Investigator: Rathore

Sponsors and Collaborators

Roger Williams Medical Center

TriSalus Life Sciences

Investigators

• Principal Investigator: Rathore; Roger Williams Medical Center

More Information

• Responsible Party: Ritesh Rathore, MD, Director, Division of Hematology/Oncology, Roger Williams Medical Center
• ClinicalTrials.gov Identifier: NCT04270929
• Other Study ID Numbers: 342-30
• First Posted: February 17, 2020
• Last Update Posted: May 27, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ritesh Rathore, MD, Roger Williams Medical Center:

Unresectable Pancreatic Cancer; Metastatic Pancreatic Cancer; Oxaliplatin; Pancreatic Cancer

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Folfirinox; Antineoplastic Agents