Intra-arterial Gemcitabine Vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC
- Conditions
- Locally Advanced Pancreatic Cancer
- Interventions
- Registration Number
- NCT03257033
- Lead Sponsor
- RenovoRx
- Brief Summary
The study is a multi-center, open-label, randomized active controlled study of subjects with locally advanced pancreatic adenocarcinoma which is unresectable.
- Detailed Description
All subjects will receive induction therapy of IV gemcitabine plus nab-paclitaxel, as well as SBRT radiation therapy for approximately a total of four months. Subjects who remain eligible will then be randomized to receive either intra-arterial chemotherapy with gemcitabine; or to continue gemcitabine plus nab-paclitaxel. Subjects will receive the randomized treatments for up to 16 weeks or until progression. Both groups will receive either IV gemcitabine and nab-paclitaxel or oral capecitabine following the 16-week treatment course until disease progression at the discretion of the Investigator and then followed for survival for five years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 190
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Histologically or Cytopathology confirmed pancreatic adenocarcinoma with initial diagnosis within 6 weeks of consent for patients who enroll at cycle 1, and from the start of cycle 1 of gemcitabine + nab-paclitaxel chemotherapy for patients who enroll at cycle 2
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Locally advanced, unresectable disease at screening and prior to randomization, as defined by NCCN criteria determined by an on-site, experienced, multidisciplinary team (as confirmed by CT or MRI within 30 days of the start of cycle 1)
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Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
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Age ≥ 18 years
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Adequate laboratory values prior to receiving the first dose of nab-paclitaxel and gemcitabine: (criterion must be met prior to cycle 2.) For a subject with elevated bilirubin, AST or ALT, who has had a biliary stent placed, if the subject's lab values have returned to within the required range for eligibility noted below in sub-criteria e and f [(AST) ALT ≤ 3.0 X the upper normal limit, and total bilirubin ≤ 1.5 X the upper normal limit] after placement of stent and prior to cycle 2, he/she is eligible for the study. Additional detail regarding eligibility for subjects who have had biliary stents recently placed is outlined in sub-criteria f and h below.
- Absolute neutrophil count (ANC) ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 9.0 g/dL
- Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine >1.5 mg/dL
- *Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 X the upper normal limit of institution's normal range
- *Total bilirubin ≤ 1.5 X the upper normal limit of institution's normal range -OR- If biliary stent is placed or planned to be placed within 6 weeks of Cycle 1 Day 1 (C1D1), total bilirubin ≤ 2.0 X the upper normal limit of institution's normal range (see section 9.1.4 for dose modification due to elevated bilirubin)
- Prothrombin time (PT) and partial thromboplastin time (PTT) must be ≤ 1.5 X upper normal limit of institution's normal range. Subjects who are currently taking anti-coagulant therapy are eligible if not meeting this criterion
- International normalized ration (INR) ≤ 1.5 X upper normal limit of institution's normal range. Subjects who are currently taking anti-coagulant therapy are eligible if not meeting this criterion *For elevated AST, ALT, and total bilirubin at screening, subject must have a normalized result prior to initiation of Cycle 2 if abnormal labs are considered related to bile duct obstruction and a biliary stent has been placed
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Life expectancy > 12 weeks
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Negative pregnancy test for women of childbearing potential (either serum or urine) within one day prior to administration of the first dose of chemotherapy. Women of childbearing potential should use highly effective methods of contraception during treatment and for up to 6 months following treatment cessation
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Provide written informed consent
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Subjects willing to participate in the study for at least 8 months if randomized to IA gemcitabine OR IV gemcitabine + nab-paclitaxel
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Any prior treatment for pancreatic cancer OR more than one cycle of gemcitabine and nab-paclitaxel treatment. For subjects who have started on their first cycle of gemcitabine and nab-paclitaxel treatment prior to consent, Inclusion Criterion #1 only applies to the first gemcitabine and nab-paclitaxel dose and must be within 6 weeks of confirmed diagnosis
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Any evidence of metastatic disease or another active malignancy within the past one year except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
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Subjects unable or unwilling to have their first randomized treatment within 3 weeks of the post induction imaging and within 5 weeks of their last induction treatment
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Subjects without baseline tumor imaging
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As determined by the Sponsor:
Arterial anatomy unsuitable for IA delivery of gemcitabine to the intended tumor site, determined by CT or MRI, as determined and approved by the Sponsor Imaging Advisor, which includes the following:
- Stenosis or occlusion in the intended artery for treatment
- Inability to exclude major side branches in the area of the intended RenovoCath® catheter occlusion
- No suitable artery with a diameter greater than 3 mm in proximity of at least one side of the tumor
- Superior mesenteric vein (SMV) occlusion or stenosis that cannot be resolved with medication or intervention prior to randomization, if the superior mesenteric artery (SMA) is the only viable treatment artery Note: Arterial Anatomy will be reviewed by the Sponsor, RenovoRx Imaging Advisor, and RenovoRx Medical Monitor for approval
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Contraindications for SBRT planning which includes the following:
- Gastrointestinal mucosal infiltration evident at the time of diagnostic endoscopy
- Prior abdominal radiotherapy judged to have clinically significant degree of overlap with planned SBRT dose distribution Note: Primary tumors with a diameter greater than 7 cm must be assessed on a case-by-case basis with the RenovoRx Imaging Advisor prior to excluding the subject from the trial.
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Subjects with known HIV infection or active viral hepatitis
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Severe infections requiring hospitalization within 4 weeks prior to the first study treatment, including but not limited to complications of infection, bacteremia or severe pneumonia
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Signs or symptoms of infection within 2 weeks prior to the first study treatment, as assessed by the Investigator
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Received antibiotics for treatment of an infection within 48 hours prior to initiation of study treatment. Subjects receiving prophylactic antibiotics are eligible
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History of severe allergic, anaphylactic, or other hypersensitivity reactions to gemcitabine or nab-paclitaxel
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Any anti-cancer therapy including chemotherapy, hormonal therapy for prostate cancer, or radiotherapy within 2 weeks prior to initiation of study treatment; or herbal therapy intended as anti-cancer therapy within 1 week prior to initiation of study treatment
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Subjects with uncontrolled seizures
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Cardiovascular disease including unstable angina or life-threatening cardiac arrhythmia, myocardial infarction, stroke; or New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) within the last 3 months prior to the first study treatment. Subjects with prior history of Myocardial Infarction (MI), congestive heart failure (CHF), coronary artery bypass grafting, or prior valve surgery need to have assessment of ejection fraction (EF) to ensure EF is not ≤ 40% (as determined by MRI, ECHO, or Nuclear Scan), within the last 3 months prior to the initiation of study treatment
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Other severe concurrent disease or comorbidities which make it difficult to participate in this study, as assessed by Investigator
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Any of the following procedures prior to initiation of study treatment:
- Catheterization, endoscopy, stent or drain placement within 48 hours. (Diagnostic laparoscopy without surgical intervention and/or port placement do not require any wait time prior to study treatment)
- Minor surgery requiring light sedation (such as surgical laparoscopy) within 2 weeks
- Major surgery within 4 weeks
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Women who are breastfeeding
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Male or female subjects of reproductive potential who do not agree to either remain abstinent or employ highly effective and acceptable forms of contraception throughout their participation in the study and for 6 months after the last study treatment
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Subjects receiving any other investigational agents within 2 weeks prior to the initiation of treatment
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Any social situations or psychiatric illness that would limit compliance with study requirements
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Subjects unable or unwilling to have standard catheterization procedure
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IA Therapy Gemcitabine IA Treatments with 1,000 mg/m2 gemcitabine administered through RenovoCath every other week for a maximum of 8 treatments for approximately 16 weeks. IA Therapy RenovoCath IA Treatments with 1,000 mg/m2 gemcitabine administered through RenovoCath every other week for a maximum of 8 treatments for approximately 16 weeks. IV Therapy nab-paclitaxel IV gemcitabine and nab-paclitaxel will be administered for 16 weeks on days 1, 8, and 15 of a 28 day cycle. Nab-paclitaxel will be administered intravenously following pre-medication at a dose of 125 mg/m2 over 30 minutes followed by an infusion of gemcitabine at a dose of 1000 mg/m2 over 30 minutes. IV Therapy Gemcitabine IV gemcitabine and nab-paclitaxel will be administered for 16 weeks on days 1, 8, and 15 of a 28 day cycle. Nab-paclitaxel will be administered intravenously following pre-medication at a dose of 125 mg/m2 over 30 minutes followed by an infusion of gemcitabine at a dose of 1000 mg/m2 over 30 minutes.
- Primary Outcome Measures
Name Time Method Overall Survival Up to Five Years OS from time of randomization will be calculated using the Kaplan-Meier method and compared between the test and control groups using the stratified Log-Rank Test
- Secondary Outcome Measures
Name Time Method Progression Free Survival Up to Five Years To compare the Progression Free Survival of intra-arterial delivery of gemcitabine using the RenovoCath™ device vs. continuation of IV gemcitabine and nab-paclitaxel following induction therapy with gemcitabine and nab-paclitaxel and radiation treatment for locally advanced pancreatic adenocarcinoma. Disease response and progression will be assessed according to RECIST 1.1.
Safety, defined as adverse event rate, and tolerability, defined as occurrence of treatment discontinuation Up to Five Years Safety and tolerability will be assessed by the occurrence of treatment discontinuation and the presence of adverse events
Overall Survival for treatment received and unresected populations Up to Five Years The primary endpoint analysis will be repeated for the Treatment Received and Unresected Subject populations.
Objective response rate and duration of response Up to Five Years Objective response is defined as a complete response, CR, or partial response, PR, determined by Investigator assessment and confirmed by repeat assessment ≥ 4 weeks after initial documentation.
Frequency of neutropenia 1 Year Neutropenia with onset after randomization requiring the use of filgrastim or other medications for white blood cell stimulation will be compared between the test and control groups through progression of disease.
Health Related Quality of Life Up to Five Years The EORTC questionnaire will be used to assess health related quality of life. The summary scores for the EORTC questionnaire will be calculated at baseline and follow-up.
Neuropathy Assessment 1 Year The degree of neuropathy will be measured by the FACT/GOG-NTX-4 (version 4). The results will be cross tabulated by randomized treatment group for each study visit.
Patient reported symptoms Up to Five Years Symptoms reported by subjects using the PRO-CTCAE questionnaire will be compared between the test and control groups through progression of disease.
Trial Locations
- Locations (41)
Feinstein Institutes for Medical Research - Northwell Health
🇺🇸Manhasset, New York, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
VA Loma Linda Healthcare System
🇺🇸Loma Linda, California, United States
Sutter Cancer Center Sacramento
🇺🇸Sacramento, California, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Comprehensive Cancer Care and Research Institute of Colorado, CCCRIC
🇺🇸Englewood, Colorado, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
21st Century Oncology
🇺🇸Fort Myers, Florida, United States
Miami Cancer Center
🇺🇸Miami, Florida, United States
Sarasota Memorial Health Care System
🇺🇸Sarasota, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
ASCLEPES Research Centers
🇺🇸Weeki Wachee, Florida, United States
Piedmont-Columbus Regional - John B. Amos Cancer Center
🇺🇸Columbus, Georgia, United States
University of Iowa Hospitals and Clinics - Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
LSU Health Shreveport
🇺🇸Shreveport, Louisiana, United States
Medstar Franklin Square
🇺🇸Baltimore, Maryland, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
MD Anderson Cancer Center at Cooper Hospital
🇺🇸Camden, New Jersey, United States
Atlantic Health System - Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Albany Stratton VA Medical Center
🇺🇸Albany, New York, United States
Montefiore Hospital
🇺🇸Bronx, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Levine Cancer Institute - Atrium Health
🇺🇸Charlotte, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Wake Forest Baptist Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Oklahoma University - Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina - Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Prisma Health (formerly Greenville Health System)
🇺🇸Greenville, South Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
VA Puget Sound Health Care System
🇺🇸Seattle, Washington, United States
West Virginia University Medicine
🇺🇸Morgantown, West Virginia, United States
AZ Sint-Lucas
🇧🇪Brugge, Belgium
UZ Antwerp
🇧🇪Edegem, Belgium
AZ Maria Middelares
🇧🇪Gent, Belgium
UZ Gent
🇧🇪Gent, Belgium
Jolimont Hospital
🇧🇪La Louvière, Belgium
AZ Delta
🇧🇪Roeselare, Belgium