Intra-arterial vs. IV Chemotherapy for Pancreatic Cancer

(TIGeR-PaC Trial)

Recruiting in Palo Alto (17 mi)

+21 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests different ways to treat advanced pancreatic cancer that can't be removed by surgery. It uses a combination of chemotherapy drugs and radiation, then compares direct artery chemotherapy to other treatments.

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.

What data supports the effectiveness of this treatment for pancreatic cancer?

Research shows that delivering gemcitabine directly into the pancreas through intra-arterial (IA) injection significantly reduces tumor growth more effectively than the same dose given through standard intravenous (IV) injection. Additionally, combining nab-paclitaxel with gemcitabine has been shown to improve tumor response and survival rates in advanced pancreatic cancer compared to gemcitabine alone. ^{1 2 3 4 5}

Is the combination of nab-paclitaxel and gemcitabine safe for treating pancreatic cancer?

The combination of nab-paclitaxel (Abraxane) and gemcitabine has been studied in several trials for pancreatic cancer, showing manageable side effects similar to those reported in the MPACT trial, which suggests it is generally safe for use in humans. ^{6 7 8 9 10}

What makes the intra-arterial delivery of gemcitabine and nab-paclitaxel unique for pancreatic cancer treatment?

The intra-arterial delivery of gemcitabine directly into the pancreas allows for a higher concentration of the drug to reach the tumor with less systemic exposure, potentially leading to better tumor reduction compared to traditional intravenous methods, which require much higher doses to achieve similar effects. ^{1 3 4 7 11}

Research Team

Michael J Pishvaian

Principal Investigator

Johns Hopkins Kimmel Cancer Center

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Gemcitabine (Anti-metabolites)
• nab-paclitaxel (Other)
• RenovoCath (Other)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. England 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. [2022]

2. India pubmed.ncbi.nlm.nih.gov

Pancreatic intra-arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma: A pilot study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

5. England 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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

9. England 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. [2022]

10. China pubmed.ncbi.nlm.nih.gov

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. [2020]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel: potential for the treatment of advanced pancreatic cancer. [2021]