Intra-arterial vs. IV Chemotherapy for Pancreatic Cancer

(TIGeR-PaC Trial)

Recruiting at 19 trial locations

Overseen By Leesa Gentry

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: RenovoRx

Must be taking: Gemcitabine, Nab-paclitaxel

Must not be taking: Antibiotics, Anticancer therapy

Disqualifiers: Metastatic disease, Active malignancy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two methods of delivering chemotherapy for pancreatic cancer that cannot be surgically removed. One group will receive gemcitabine and nab-paclitaxel through an IV, while the other group will receive gemcitabine directly into the artery near the tumor. The trial aims to determine which method is more effective for advanced pancreatic cancer. Individuals diagnosed with this type of cancer within the last six weeks who have not yet received major treatments may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have had any anti-cancer therapy, including chemotherapy or radiotherapy, within 2 weeks before starting the study treatment. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that using the RenovoCath device to deliver gemcitabine may offer safety benefits. This method targets the drug directly to the pancreas, potentially reducing side effects elsewhere in the body.

In a previous study, patients handled this targeted delivery well. Some research even suggests it might lower the risk of serious side effects. Additionally, the FDA has already approved gemcitabine for other uses, indicating its general safety for humans.

For intravenous (IV) treatment, gemcitabine is often combined with nab-paclitaxel for pancreatic cancer. Past patients have generally tolerated these drugs well, although they can still cause side effects like tiredness or nausea.

Overall, both treatments have safety records suggesting they are well-tolerated by most patients. However, as with any treatment, individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the new approaches to delivering chemotherapy for pancreatic cancer because they offer innovative ways to attack the disease. Unlike the standard intravenous (IV) chemotherapy, which is administered through a vein, the investigational intra-arterial (IA) method delivers chemotherapy directly to the pancreas through the arteries. This targeted delivery could mean higher concentrations of the drug reach the tumor, potentially increasing its effectiveness while minimizing side effects elsewhere in the body. The IA approach uses a device called RenovoCath, which allows for precise delivery of gemcitabine, making it a promising alternative to traditional methods.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

This trial will compare two treatment approaches for advanced pancreatic cancer. One arm delivers the drug gemcitabine directly into the arteries using a device called RenovoCath. Research has shown this method to be promising, with nearly 60% of patients surviving for 12 months, a significant improvement over past methods. This approach appears to deliver the drug to the tumor more effectively, potentially enhancing its efficacy and resulting in fewer side effects, making it a more comfortable option.

The other arm administers gemcitabine through an IV along with nab-paclitaxel, a common treatment. This combination has proven effective in shrinking tumors and extending patients' lives. Both treatments in this trial offer hope for better results in fighting this challenging disease. ^{1 2 4 6 7}

Who Is on the Research Team?

Michael J Pishvaian

Principal Investigator

Johns Hopkins Kimmel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, locally advanced pancreatic cancer that can't be surgically removed. They should have a life expectancy over 12 weeks, good physical function, and proper organ function. Women must not be pregnant and agree to contraception use. People are excluded if they've had certain treatments or surgeries recently, have metastatic disease or other cancers within the last year, severe infections or heart conditions in recent months, HIV/hepatitis, or allergies to the drugs being tested.

Inclusion Criteria

Histologically or Cytopathology confirmed pancreatic adenocarcinoma with initial diagnosis within 6 weeks of consent

You are expected to live for at least 12 more weeks.

ECOG performance status 0-1

Exclusion Criteria

- Contraindications for SBRT planning which includes the following:

-- Gastrointestinal mucosal infiltration evident at the time of diagnostic endoscopy

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive IV gemcitabine plus nab-paclitaxel and SBRT radiation therapy

16 weeks

Randomized Treatment

Participants receive either intra-arterial chemotherapy with gemcitabine or continue with IV gemcitabine plus nab-paclitaxel

16 weeks

Continuation Therapy

Participants receive either IV gemcitabine and nab-paclitaxel or oral capecitabine until disease progression

Follow-up

Participants are monitored for survival and other outcomes

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• nab-paclitaxel
• RenovoCath

Trial Overview

The study compares two ways of delivering chemotherapy for pancreatic cancer: directly into the artery feeding the tumor (intra-arterial) using RenovoCath versus standard IV infusion. Both groups will receive Gemcitabine and nab-Paclitaxel following radiotherapy to see which method is more effective.

How Is the Trial Designed?

Group I: IA Therapy Experimental Treatment 2 Interventions

IA Treatments with 1,000 mg/m2 gemcitabine administered through RenovoCath every other week for a maximum of 8 treatments for approximately 16 weeks.

Group II: IV Therapy Active Control 2 Interventions

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.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

RenovoRx

Lead Sponsor

Trials

4

Recruited

1,200+

Published Research Related to This Trial

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

In a study of patients with resected pancreatic ductal adenocarcinoma (PDAC), adjuvant chemotherapy with nab-paclitaxel plus gemcitabine (AG) significantly improved median disease-free survival (15.8 months) and overall survival (28.3 months) compared to gemcitabine alone (12.2 months and 20.6 months, respectively).

While AG showed better survival outcomes, it also led to a higher incidence of sensory neuropathy (53.3% in AG vs. 23.3% in GEM), indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. Yin, ZZ., Zhao, ZM., Tang, WB., et al.[2020]

Pancreatic intra-arterial infusion chemotherapy (PAIC) with nab-paclitaxel was found to be safe and well-tolerated in 15 patients with advanced pancreatic carcinoma, with no procedure-related complications reported.

The treatment resulted in significant clinical benefits, including an 86.67% clinical benefit response rate and a median overall survival of 8.97 months, indicating its potential effectiveness in improving patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic intra-arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma: A pilot study. Wang, N., Xu, J., Wang, G., et al.[2023]

Nabpaclitaxel plus S-1 (AS) significantly improved median time to progression (7.1 months) and overall survival (10.2 months) compared to gemcitabine plus S-1 (GS), indicating AS may be a more effective first-line treatment for metastatic pancreatic cancer based on a study of 38 patients.

While both treatments had similar rates of hematological adverse events, AS was associated with a higher risk of sensory neuropathy, suggesting that while AS is effective, it requires careful monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety comparison of nabpaclitaxel plus S-1 and gemcitabine plus S-1 as first-line chemotherapy for metastatic pancreatic cancer. Xu, Y., Guo, X., Fan, Y., et al.[2022]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a large Phase III clinical trial, the combination of nab-paclitaxel and gemcitabine significantly improved treatment outcomes for advanced pancreatic adenocarcinoma, increasing the response rate from 7% to 23%.

Patients receiving the combination therapy also experienced longer progression-free survival (5.5 months compared to 3.7 months) and overall survival (8.5 months compared to 6.7 months) compared to those treated with gemcitabine alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel: potential for the treatment of advanced pancreatic cancer. Al-Hajeili, M., Azmi, AS., Choi, M.[2021]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

Targeted intra-arterial (IA) delivery of gemcitabine directly into the pancreas significantly reduces tumor growth in a mouse model of pancreatic cancer compared to low-dose systemic intravenous (IV) delivery.

To achieve similar tumor reduction effects as IA delivery, a much higher IV dose (over 300 times) is required, which can lead to increased toxicity, highlighting the efficacy and safety benefits of the IA approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Study Comparing the Effects of Targeted Intra-Arterial and Systemic Chemotherapy in an Orthotopic Mouse Model of Pancreatic Cancer. Rezaee, M., Wang, J., Razavi, M., et al.[2022]

A retrospective analysis of 59 patients with advanced refractory pancreatic cancer showed that the combination of nab-paclitaxel and gemcitabine (AG) is active as a second-line or beyond treatment, with 10% achieving a partial response and 47% having stable disease.

The median overall survival was 3.9 months and progression-free survival was 3 months, with toxicity levels similar to those reported in the earlier MPACT trial, indicating that AG has manageable side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. Palacio, S., Hosein, PJ., Reis, I., et al.[2020]

The NEONAX trial is a large, phase II study involving 166 patients with resectable pancreatic ductal adenocarcinoma, comparing the efficacy of perioperative chemotherapy (nab-paclitaxel and gemcitabine) against standard adjuvant therapy to improve disease-free survival (DFS) at 18 months.

Preliminary evidence suggests that nab-paclitaxel/gemcitabine has a favorable toxicity profile compared to FOLFIRINOX, making it a promising option for patients undergoing surgery for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group. Ettrich, TJ., Berger, AW., Perkhofer, L., et al.[2022]

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