Lonsurf + Chemotherapy for Pancreatic Cancer

Overseen By John Spittler, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Patrick Joseph Loehrer Sr.

Must not be taking: Taxanes

Disqualifiers: Active malignancy, Brain metastases, others

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

Compensation: Varies

Number of Visits: 1

Duration: up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of three drugs—Lonsurf, gemcitabine, and nab-paclitaxel—to determine the optimal dose for treating pancreatic cancer. It targets individuals with untreated pancreatic ductal adenocarcinoma, whether locally advanced or metastatic. Participants should have manageable gastrointestinal symptoms and must not have received certain prior cancer treatments. The study aims to advance treatment for this challenging cancer by testing the effectiveness of this drug combination. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that using nab-paclitaxel and gemcitabine together is generally safe for treating pancreatic cancer. Common side effects include low blood cell counts and tiredness, but these can usually be managed. Evidence also suggests that this drug combination can help patients live longer.

Lonsurf is currently being tested with these two drugs. In this Phase 1 trial, researchers are primarily assessing the safety of the new combination and determining the optimal dose. While detailed safety information for this specific mix is not yet available, nab-paclitaxel and gemcitabine have been used together before, and their side effects are well-documented.

In summary, while the safety of the new combination with Lonsurf is still under investigation, the existing treatments it is paired with are known to be generally safe for pancreatic cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about the combination of Lonsurf with gemcitabine and nab-paclitaxel for pancreatic cancer because it introduces a new way to tackle the disease. Unlike the standard treatments, which often rely on gemcitabine alone or in combination with nab-paclitaxel, this approach adds Lonsurf, which works by interfering with the cancer cells' ability to make DNA, potentially making it more effective. This cocktail of drugs might target the cancer more comprehensively, possibly leading to better outcomes for patients. Additionally, this combination could offer hope for those who have limited response to existing therapies.

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

Research has shown that using nab-paclitaxel with gemcitabine can extend the lives of adults with advanced pancreatic cancer. On average, patients receiving this combination lived 8.5 months, compared to 6.7 months with gemcitabine alone. Nab-paclitaxel shrinks tumors, enhancing treatment effectiveness. In this trial, researchers are examining whether adding Lonsurf to these drugs can further improve outcomes. This combination targets pancreatic ductal adenocarcinoma, a type of pancreatic cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Patrick J Loehrer, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for adults with confirmed pancreatic ductal adenocarcinoma (PDAC) who have adequate organ function and can consent to treatment. Women must not be pregnant and participants must agree to use contraception. Exclusions include recent major surgery, bowel obstruction, uncontrolled illnesses or infections, certain heart conditions, known hypersensitivity to study drugs, neuropathy greater than Grade 1, untreated brain metastases, or prior chemotherapy for other cancers within the last three years.

Inclusion Criteria

You have been diagnosed with pancreatic cancer through a tissue or cell sample.

Ability to provide written informed consent and HIPAA authorization

Adequate organ function as defined by:

Exclusion Criteria

You have had a blockage in your intestines or stomach in the past 3 months, including blockages related to pancreatic cancer.

You have a large amount of fluid in your abdomen that needs to be drained regularly.

Major surgery, other than diagnostic or laparoscopic surgery, within 4 weeks prior to first dose. (Port placement would not be considered a surgery.)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of lonsurf, gemcitabine, and nab-paclitaxel to determine the recommended phase 2 dose (RP2D)

up to 2 years

Day 1 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after treatment discontinuation

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Lonsurf
• Nab-Paclitaxel

Trial Overview The trial is testing the combination of Lonsurf with Gemcitabine and Nab-Paclitaxel in patients with advanced PDAC. The goal is to determine the safest and most effective dose level for this drug combination.

How Is the Trial Designed?

Group I: Combination of lonsurf + gemcitabine + nab-paclitaxel Experimental Treatment 3 Interventions

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?

Patrick Joseph Loehrer Sr.

Lead Sponsor

Trials

5

Recruited

60+

Taiho Oncology, Inc.

Industry Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Indiana University

Collaborator

Trials

1,063

Recruited

1,182,000+

Published Research Related to This Trial

Nab-paclitaxel, when combined with gemcitabine, significantly improves overall survival in adults with metastatic pancreatic cancer, reducing the risk of death by 28% compared to gemcitabine alone, based on a multinational phase III study.

The treatment has a manageable safety profile, with most adverse events being grade 3 or lower, and common side effects like neutropenia and peripheral neuropathy are generally reversible with dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel: a review of its use for the first-line combination treatment of metastatic pancreatic cancer. Hoy, SM.[2021]

In a study of 11 patients with metastatic or recurrent pancreatic cancer, the combination of nab-paclitaxel and gemcitabine showed promising efficacy, with a 6-month overall survival rate of 66.7% and a disease control rate of 90.9%.

The treatment was well tolerated, with no treatment-related deaths and manageable side effects, making nab-paclitaxel plus gemcitabine a potential standard treatment for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. Takeda, Y., Katsura, Y., Ohmura, Y., et al.[2022]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

In a phase II trial involving 61 patients with borderline resectable pancreatic cancer, the neoadjuvant therapy of nab-paclitaxel plus gemcitabine resulted in a median overall survival of 25.2 months and a median recurrence-free survival of 12.3 months, indicating promising efficacy.

The treatment had a high resection rate of 73.8% and an R0 resection rate of 63.9%, but it also presented significant safety concerns, with 73.8% of patients experiencing grade 3/4 adverse events, highlighting the need for careful patient selection, especially for those with prior lung issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial). Okada, KI., Kimura, K., Yamashita, YI., et al.[2023]

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 retrospective study of 29 patients with advanced pancreatic carcinoma and elevated bilirubin levels, treatment with nanoparticle albumin-bound paclitaxel and gemcitabine (nab-P/G) was found to be safe, showing no unexpected toxicities.

The median overall survival for patients treated with nab-P/G was 11.7 months, with no significant differences in survival based on bilirubin levels, indicating that nab-P/G is a feasible treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. Pelzer, U., Wislocka, L., Jühling, A., et al.[2022]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-1-adenocarcinoma-7-2019-124af

Lonsurf + Chemotherapy for Pancreatic Cancer Nab-paclitaxel, when combined with gemcitabine, significantly improves overall survival in adults with metastatic pancreatic cancer, reducing the risk of death ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04046887

Study of Lonsurf in Combination With Gemcitabine and ... This is a single-institution, prospective, phase I dose escalation trial of lonsurf combined with gemcitabine and nab-paclitaxel using the 3+3 design.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4631139/

Increased Survival in Pancreatic Cancer with nab-Paclitaxel ... Among patients with metastatic disease, the 5-year survival rate is only 2%, and 1-year survival rates of 17 to 23% have been reported with gemcitabine.

4. cancer.gov cancer.gov/types/pancreatic/research/nab-paclitaxel-gemcitabine

Nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic ... Patients who received the drug combination had a median overall survival of 8.5 months, compared with 6.7 months for patients treated with gemcitabine alone.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10915801/

Efficacy of nab‑paclitaxel vs. Gemcitabine in combination with ... Efficacy of nab‐paclitaxel vs. Gemcitabine in combination with S‐1 for advanced pancreatic cancer: A multicenter phase II randomized trial

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04046887/study-of-lonsurf-in-combination-with-gemcitabine-and-nab-paclitaxel-in-patients-with-advanced-pdac

Study of Lonsurf in Combination With Gemcitabine and ... The purpose of this study is to determine the recommended phase 2 dose (RP2D) of the combination of lonsurf, gemcitabine and nab-paclitaxel ...