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

• Status: Recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: RenovoRx
• Treatments: Albumin-Bound Paclitaxel; Gemcitabine; Paclitaxel

Criteria

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 (as confirmed by CT or MRI within 30 days of the first on study treatment).

3. ECOG performance status 0-1

4. Age ≥ 18 years

5. Absolute neutrophil count ≥ 1,500/μL

6. Platelet count ≥ 100,000/μL

7. Hemoglobin ≥ 9.0 g/dL

8. Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine >1.5 mg/dL

9. AST and ALT ≤ 3.0 X the upper normal limit of institution's normal range

10. Prior to the initiation of the first on study treatment (Cycle 1/Day 1):

1. Total bilirubin ≤ 1.5 X the upper normal limit of institution's normal range, or

2. Total bilirubin ≤ 2.0 X the upper normal limit of institution's normal range if biliary stent placed or planned to be placed within 6 weeks of Cycle 1/Day 1

11. PT and PTT must be ≤ 1.5 X upper normal limit of institution's normal range

12. INR ≤ 1.5

13. Life expectancy > 12 weeks

14. Women of childbearing potential must have a negative serum or urine pregnancy test 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.

15. Provide written informed consent

16. Subjects willing to participate in the study for at least 8 months

Exclusion Criteria:

1. Any prior treatment for pancreatic cancer. If all other inclusion/exclusion criteria are met, and with prior written approval from sponsor, an exception may be granted for subjects who have had up to one prior treatment cycle with gemcitabine/nab-paclitaxel as this regimen is standard of care and part of the initial induction treatment on the protocol. 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/nab-paclitaxel dose must be within six weeks of 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 three weeks of the post induction imaging and within 5 weeks of their last induction treatment

4. Subjects without baseline tumor imaging

5. Anatomy suitable for IA delivery of gemcitabine to the intended tumor site, determined by CT or MRI, as determined by the sponsor, which precludes the following:

1. Stenosis or occlusion in intended artery for treatment

2. Tortuosity preventing the delivery of the guide sheath and or RenovoCath® catheter to intended site

3. Inability to exclude major side branches in the area of the intended RenovoCath® occlusion

4. No suitable artery with a diameter greater than 3mm in proximity of at least one side of the tumor Note: Suitable anatomy will be reviewed by RenovoRx Imaging Advisor after receipt of initial CT or MRI.

6. Subjects with known HIV or active viral hepatitis

7. 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

8. Signs or symptoms of infection within 2 weeks prior to the first study treatment

9. Received oral or IV antibiotics for an infection within 2 weeks prior to the first study treatment. Subjects receiving prophylactic antibiotics are eligible.

10. History of severe allergic, anaphylactic, or other hypersensitivity reactions to gemcitabine or nab-paclitaxel

11. 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

12. Subjects with uncontrolled seizures

13. 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 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%, within last 3 months prior to the first study treatment.

14. Life-threatening visceral disease, other severe concurrent disease, or comorbidities which make it difficult to participate in the study

15. Any of the following procedures prior to initiation of study treatment:

1. Catheterization, endoscopy, stent or drain placement, within 48 hours, and laparoscopy without surgical intervention can be in less than 48 hours

2. Minor surgery requiring light sedation, (such as surgical laparoscopy) within 2 weeks

3. Major surgery within 4 weeks

16. Women who are breastfeeding

17. Male or female subjects of reproductive potential who do not agree to employ two highly effective and acceptable forms of contraception throughout their participation in the study and for 6 months after last study treatment

18. Subjects receiving any other investigational agents within 2 weeks prior to the first study treatment

19. Any psychiatric illness or social situations that would limit compliance with study requirements

20. Subjects unable or unwilling to have standard catheterization procedure.