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Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC (TIGeR-PaC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03257033
Recruitment Status : Unknown
Verified February 2022 by RenovoRx.
Recruitment status was:  Recruiting
First Posted : August 22, 2017
Last Update Posted : February 25, 2022
Sponsor:
Information provided by (Responsible Party):
RenovoRx

Tracking Information
First Submitted Date  ICMJE August 17, 2017
First Posted Date  ICMJE August 22, 2017
Last Update Posted Date February 25, 2022
Actual Study Start Date  ICMJE March 12, 2018
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
Overall Survival [ Time Frame: 3 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
Original Primary Outcome Measures  ICMJE
 (submitted: August 17, 2017)
Progression Free Survival [ Time Frame: 3 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
  • Overall Survival for treatment received and unresected populations [ Time Frame: 3 Years ]
    The primary endpoint analysis will be repeated for the Treatment Received and Unresected Subject populations.
  • Progression Free Survival [ Time Frame: 3 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.
  • Objective response rate and duration of response [ Time Frame: 3 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.
  • Health Related Quality of Life [ Time Frame: 3 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 [ Time Frame: 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.
  • Frequency of neutropenia [ Time Frame: 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.
  • Patient reported symptoms [ Time Frame: 3 years ]
    Symptoms reported by subjects using the PRO-CTCAE questionnaire will be compared between the test and control groups through progression of disease.
  • Safety, defined as adverse event rate, and tolerability, defined as occurrence of treatment discontinuation [ Time Frame: 3 years ]
    Safety and tolerability will be assessed by the occurrence of treatment discontinuation and the presence of adverse events
Original Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2017)
  • Disease Free Survival [ Time Frame: 3 Years ]
    The primary endpoint analysis will be repeated for the Treatment Received and Unresected Subject populations.
  • Overall Survival [ Time Frame: 3 Years ]
    OS from time of diagnosis will be calculated using the Kaplan-Meier method and compared between the test and control groups using the stratified Log-Rank Test and Cox Proportional Hazard model. Surviving subjects will be censored at the latest time that survival was confirmed. Survival time will be calculated from time of histology confirmed diagnosis to death.
  • Objective response rate and duration of response [ Time Frame: 3 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.
  • Health Related Quality of Life [ Time Frame: 3 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.
  • Degree of peripheral neuropathy [ Time Frame: 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.
  • Frequency of neutropenia [ Time Frame: 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.
  • Tolerability and safety of the control and test groups [ Time Frame: 3 years ]
    Safety and tolerability will be assessed by the occurrence of treatment discontinuation and the presence of adverse events
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC
Official Title  ICMJE 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
Brief Summary The study is a multi-center, un-blinded, randomized control 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 radiation therapy for approximately 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced Pancreatic Cancer
Intervention  ICMJE
  • Drug: Gemcitabine
    Chemotherapy
    Other Name: Gemzar
  • Drug: nab-paclitaxel
    Chemotherapy
    Other Name: Abraxane
  • Device: RenovoCath
    Intra-arterial catheter
    Other Name: RenovoCath RC120
Study Arms  ICMJE
  • Experimental: IA Therapy
    IA Treatments with 1,000 mg/m2 gemcitabine administered through RenovoCath every other week for a maximum of 8 treatments for approximately 16 weeks.
    Interventions:
    • Drug: Gemcitabine
    • Device: RenovoCath
  • Active Comparator: IV Therapy
    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.
    Interventions:
    • Drug: Gemcitabine
    • Drug: nab-paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 16, 2019)
320
Original Estimated Enrollment  ICMJE
 (submitted: August 17, 2017)
200
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically or Cytopathology confirmed pancreatic adenocarcinoma with initial diagnosis within 6 weeks of consent.
  2. Locally advanced, unresectable disease at screening and prior to randomization, as defined by NCCN criteria determined by an on-site, experienced, multidisciplinary team
  3. ECOG performance status 0-1
  4. Age ≥ 18 years
  5. Adequate laboratory values prior to starting the first dose of nab-paclitaxel and gemcitabine:

    1. Absolute neutrophil count ≥ 1,500/μL
    2. Platelet count ≥ 100,000/μL
    3. Hemoglobin ≥ 9.0 g/dL
    4. Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine >1.5 mg/dL
    5. AST and ALT ≤ 3.0 X the upper normal limit of institution's normal range
    6. Total bilirubin ≤ 1.5 X the upper normal limit of institution's normal range -OR- If biliary stent placed or planned to be placed within 6 weeks of Cycle 1 Day 1, total bilirubin ≤ 2.0 X the upper normal limit of institution's normal range
    7. PT and PTT must be ≤ 1.5 X upper normal limit of institution's normal range
    8. INR ≤ 1.5
  6. Life expectancy > 12 weeks
  7. Negative pregnancy test for women of childbearing potential (either serum or urine) within 1 day prior to administration of the first dose of chemotherapy. Women of childbearing potential should only use highly effective methods of contraception during treatment and for up to 6 months following treatment cessation.
  8. Provide written informed consent
  9. Subjects willing to participate in the study for at least 8 months

Exclusion Criteria:

  1. Any prior treatment for pancreatic cancer OR more than one cycle of gemcitabine and nab-paclitaxel treatment. For subjects who have started on first cycle of gemcitabine and nab-paclitaxel treatment prior to consent, Inclusion Criterion #1 only applies in that the first gemcitabine and nab-paclitaxel dose must be within 6 weeks of confirmed diagnosis.
  2. 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.
  3. 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
  4. Subjects without baseline tumor imaging
  5. To be determined by the sponsor and not by the site:

    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, which includes the following:

    1. Stenosis or occlusion in intended artery for treatment
    2. Inability to exclude major side branches in the area of the intended RenovoCath® catheter occlusion
    3. No suitable artery with a diameter greater than 3mm in proximity of at least one side of the tumor
    4. Superior mesenteric vein occlusion or stenosis that cannot be resolved with medication or intervention prior to randomization, if the superior mesenteric artery is the only viable treatment artery Note: Arterial Anatomy will be reviewed by the core imaging lab, RenovoRx Imaging Advisor, and RenovoRx Medical Monitor for approval
  6. Contraindications for SBRT planning which includes the following:

    1. Gastrointestinal mucosal infiltration evident at the time of diagnostic endoscopy
    2. Prior abdominal radiotherapy judged to have clinically significant degree of overlap with planned SBRT dose distribution Note: Primary tumors with a diameter greater than 7cm must be assessed on a case-by-case basis with the Central Radiation Reviewer prior to excluding patient from trial.
  7. Subjects with known HIV or active viral hepatitis
  8. Severe infections within 4 weeks prior to the first study treatment, including but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia
  9. Signs or symptoms of infection within 2 weeks prior to the first study treatment
  10. Received oral or IV antibiotics for an infection within 2 weeks prior to the first study treatment. Subjects receiving prophylactic antibiotics are eligible
  11. History of severe allergic, anaphylactic, or other hypersensitivity reactions to gemcitabine or nab-paclitaxel
  12. Any anti-cancer therapy including chemotherapy, hormonal therapy, 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
  13. Subjects with uncontrolled seizures
  14. Cardiovascular disease including unstable angina or life-threatening cardiac arrhythmia, myocardial infarction, stroke; or NYHA Class III or IV congestive heart failure within the last 3 months prior to the first study treatment. Subjects with prior history of Myocardial Infarction, congestive heart failure, coronary artery bypass grafting, or prior valve surgery need to have assessment of ejection fraction to ensure EF is not ≤ 40% (based upon MRI, ECHO, or Nuclear Scan), within last 3 months prior to the first study treatment
  15. Other severe concurrent disease, or comorbidities which make it difficult to participate in this study.
  16. Any of the following procedures prior to initiation of study treatment:

    1. 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.)
    2. Minor surgery requiring light sedation (such as surgical laparoscopy) within 2 weeks
    3. Major surgery within 4 weeks
  17. Women who are breastfeeding
  18. 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
  19. Subjects receiving any other investigational agents within 2 weeks prior to the first study treatment
  20. Any social situations or psychiatric illness that would limit compliance with study requirements
  21. Subjects unable or unwilling to have standard catherization procedure
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03257033
Other Study ID Numbers  ICMJE RR3 [CP-03-001]
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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.: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party RenovoRx
Original Responsible Party Same as current
Current Study Sponsor  ICMJE RenovoRx
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Michael J Pishvaian Johns Hopkins Kimmel Cancer Center
PRS Account RenovoRx
Verification Date February 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP