Locally Advanced Pancreatic CancerPhase 3TIGeR-PaCNCT03257033
Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC
A Phase 3 study testing Gemcitabine, nab-paclitaxel and RenovoCath in people with Locally Advanced Pancreatic Cancer, run by RenovoRx at 31 sites in 2 countries.
Trial summary
The study is a multi-center, open-label, randomized active controlled study of subjects with locally advanced pancreatic adenocarcinoma which is unresectable. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Pancreatic Cancer
- What is being tested?
- Gemcitabine, nab-paclitaxel and RenovoCath
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 31 sitesin 2 countries
- Study dates
- 12 Mar 2018to Sep 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or Cytopathology confirmed pancreatic adenocarcinoma with initial diagnosis within 8 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
- 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)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- Age ≥ 18 years
- 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 details regarding eligibility for subjects who have had biliary stents recently placed are outlined in sub-criteria f and h below.
- Absolute neutrophil count (ANC) ≥ 1,500/μL
Show all 17Show fewer
- 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
- Life expectancy > 12 weeks
- 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
- Provide written informed consent
- Subjects willing to participate in the study for at least 8 months if randomized to IA gemcitabine OR IV gemcitabine + nab-paclitaxel
Who cannot join
- 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
- 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.
- 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
- Subjects without baseline tumor imaging
- 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:
Show all 31Show fewer
- 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
- 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.
- Subjects with known HIV infection or active viral hepatitis
- 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
- Signs or symptoms of infection within 2 weeks prior to the first study treatment, as assessed by the Investigator
- Received antibiotics for treatment of an infection within 48 hours prior to initiation of study treatment. Subjects receiving prophylactic antibiotics are eligible
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to gemcitabine or nab-paclitaxel
- 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
- Subjects with uncontrolled seizures
- 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
- Other severe concurrent disease or comorbidities which make it difficult to participate in this study, as assessed by Investigator
- 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
- Women who are breastfeeding
- 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
- Subjects receiving any other investigational agents within 2 weeks prior to the initiation of treatment
- Any social situations or psychiatric illness that would limit compliance with study requirements
- Subjects unable or unwilling to have standard catheterization procedure
Trial locations and contacts
31 sites in 2 countries.
31 sites in 2 countries
United States26 sites
Medstar Franklin Square
Baltimore, Maryland, 21237
MD Anderson Cancer Center at Cooper Hospital
Camden, New Jersey, 08103
Medical University of South Carolina - Hollings Cancer Center
Charleston, South Carolina, 29425
Levine Cancer Institute - Atrium Health
Charlotte, North Carolina, 28204
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
21st Century Oncology
Fort Myers, Florida, 33907
East Carolina University
Greenville, North Carolina, 27834
Prisma Health (formerly Greenville Health System)
Greenville, South Carolina, 29605
University of Iowa Hospitals and Clinics - Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766
VA Loma Linda Healthcare System
Loma Linda, California, 92357
Feinstein Institutes for Medical Research - Northwell Health
Manhasset, New York, 11030
Miami Cancer Center
Miami, Florida, 33167
West Virginia University Medicine
Morgantown, West Virginia, 26506
Columbia University Medical Center
New York, New York, 10032
Oklahoma University - Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center
Omaha, Nebraska, 68198
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
Oregon Health & Science University
Portland, Oregon, 97239
Sutter Cancer Center Sacramento
Sacramento, California, 95816
Sarasota Memorial Health Care System
Sarasota, Florida, 34329
Moffitt Cancer Center
Tampa, Florida, 33612
Montefiore Hospital
The Bronx, New York, 10461
Sibley Memorial Hospital - a member of Johns Hopkins medicine
Washington D.C., District of Columbia, 20016
ASCLEPES Research Centers
Weeki Wachee, Florida, 34607
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
Belgium5 sites
AZ Sint-Lucas
Bruges, 8310
UZ Antwerp
Edegem, 2650
AZ Maria Middelares
Ghent, 9000
Jolimont Hospital
La Louvière, 7100
AZ Delta
Roeselare, 8800
About this study
Official title: Targeted Intra-arterial Gemcitabine vs. Continuation of IV Gemcitabine Plus Nab-Paclitaxel Following Induction With Sequential IV Gemcitabine Plus Nab-Paclitaxel and Radiotherapy for Locally Advanced Pancreatic Cancer
The study is a multi-center, open-label, randomized active controlled study of subjects with locally advanced pancreatic adenocarcinoma which is unresectable.
Read the 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.
- Conditions
- Locally Advanced Pancreatic Cancer
- Being tested
- Gemcitabine, nab-paclitaxel, RenovoCath
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemzar
Chemotherapy
nab-paclitaxelDrug
Also called Abraxane
Chemotherapy
RenovoCathDevice
Intra-arterial catheter
| Study group | Role | What they receive |
|---|---|---|
| IA Therapy | Experimental | IA Treatments with 1,000 mg/m2 gemcitabine administered through RenovoCath every other week for a maximum of 8 treatments for approximately 16 weeks. Receives: Drug: Gemcitabine; Device: RenovoCath |
| IV Therapy | Active comparator | 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. Receives: Drug: Gemcitabine; Drug: nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
OS from time of randomization will be calculated using the Kaplan-Meier method and compared between the test and control groups using the stratified Wilcoxin Test
Measured: Up to Five Years
Secondary outcomes (8)
Overall Survival for treatment received and unresected populations
The primary endpoint analysis will be repeated for the Treatment Received and Unresected Subject populations.
Measured: Up to Five Years
Progression Free Survival
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.
Measured: Up to Five Years
Objective response rate and duration of response
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.
Measured: Up to Five Years
Health Related Quality of Life
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.
Measured: Up to Five Years
Neuropathy Assessment
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.
Measured: 1 Year
Frequency of neutropenia
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.
Measured: 30 Days Post-Randomized Treatment
Frequency of Myelosuppression
Frequency of myelosuppression requiring medication for blood products to overcome anemia, neutropenia, and thrombocytopenia
Measured: 30 Days Post-Randomized Treatment
Safety, defined as adverse event rate, and tolerability, defined as occurrence of treatment discontinuation
Safety and tolerability of the drug/device combination will be assessed by the occurrence of treatment discontinuation and the presence of adverse events
Measured: Up to Five Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start12 Mar 2018
- Primary completionJun 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects with stable or responding disease after approximately four months of induction therapy, and who are not surgical candidates will then be randomized to be in either the test group or control group. Crossovers are not allowed.
- Masking
- None (open label)
- Enrolment
- 190 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenovoRx
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael J Pishvaian, Study chair, Johns Hopkins Kimmel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03257033
- Sponsor's protocol ID
- RR3 [CP-03-001]
- Acronym
- TIGeR-PaC
- Status last verified
- Sep 2026
- First submitted
- 17 Aug 2017
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
Novelli PM, Zervos EE, Zureikat AH, Pishvaian MJ, Meredith K, Hatoum H, Nazemzadeh R, Laroia S, Kasi P, Bingham J, Agah R. Pharmacokinetic and pharmacodynamic sub-study of trans-arterial vs. intravenous gemcitabine in the TIGeR-PaC phase 3 clinical trial. Cancer Chemother Pharmacol. 2026 Aug 17;96(1):91. doi: 10.1007/s00280-026-04939-0.
PubMed 42604879Farsad K, Novelli PM, Laing C, Gandhi RT, Cynamon J, Lopez CS, Stempinski ES, Strasser R, Agah R. Double-Balloon Catheter-Mediated Transarterial Chemotherapy Delivery in a Swine Model: A Mechanism Recruiting the Vasa Vasorum for Localized Therapies. J Vasc Interv Radiol. 2024 Jul;35(7):1043-1048.e3. doi: 10.1016/j.jvir.2024.03.016. Epub 2024 Mar 18.
PubMed 38508449