Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC

Locally Advanced Pancreatic Cancer Clinical Trial

— TIGeR-PaC  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03257033
• Other study ID #: RR3 [CP-03-001]
• Status: Recruiting
• Phase: Phase 3
• Start date: March 12, 2018
• Est. completion date: September 2023

Study information

• Verified date: February 2022
• Source: RenovoRx
• Contact: Carter Hultman
• Phone: 6502844433
• Email: chultman[@]renovorx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a multi-center, un-blinded, randomized control study of subjects with locally advanced pancreatic adenocarcinoma which is unresectable.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: September 2023
• Est. primary completion date: September 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Locally Advanced Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Gemcitabine
Chemotherapy
• nab-paclitaxel
Chemotherapy

Device:
• RenovoCath
Intra-arterial catheter

Locations

Country	Name	City	State
Belgium	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
United States	Albany Stratton VA Medical Center	Albany	New York
United States	Medstar Franklin Square	Baltimore	Maryland
United States	Montefiore Hospital	Bronx	New York
United States	MD Anderson Cancer Center at Cooper Hospital	Camden	New Jersey
United States	Medical University of South Carolina - Hollings Cancer Center	Charleston	South Carolina
United States	Levine Cancer Institute - Atrium Health	Charlotte	North Carolina
United States	Piedmont-Columbus Regional - John B. Amos Cancer Center	Columbus	Georgia
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Comprehensive Cancer Care and Research Institute of Colorado, CCCRIC	Englewood	Colorado
United States	21st Century Oncology	Fort Myers	Florida
United States	East Carolina University	Greenville	North Carolina
United States	Prisma Health (formerly Greenville Health System)	Greenville	South Carolina
United States	University of Iowa Hospitals and Clinics - Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	VA Loma Linda Healthcare System	Loma Linda	California
United States	Miami Cancer Institute	Miami	Florida
United States	West Virginia University Medicine	Morgantown	West Virginia
United States	Atlantic Health System - Morristown Medical Center	Morristown	New Jersey
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Oklahoma University - Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Sutter Cancer Center Sacramento	Sacramento	California
United States	Sarasota Memorial Health Care System	Sarasota	Florida
United States	VA Puget Sound Health Care System	Seattle	Washington
United States	LSU Health Shreveport	Shreveport	Louisiana
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University	Washington	District of Columbia
United States	ASCLEPES Research Centers	Weeki Wachee	Florida
United States	Wake Forest Baptist Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
RenovoRx

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 Log-Rank Test	3 Years
Secondary	Overall Survival for treatment received and unresected populations	The primary endpoint analysis will be repeated for the Treatment Received and Unresected Subject populations.	3 Years
Secondary	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.	3 Years
Secondary	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.	3 Years
Secondary	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.	3 Years
Secondary	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.	1 Year
Secondary	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.	1 Year
Secondary	Patient reported symptoms	Symptoms reported by subjects using the PRO-CTCAE questionnaire will be compared between the test and control groups through progression of disease.	3 years
Secondary	Safety, defined as adverse event rate, and tolerability, defined as occurrence of treatment discontinuation	Safety and tolerability will be assessed by the occurrence of treatment discontinuation and the presence of adverse events	3 years