Lonsurf + Chemotherapy for Pancreatic Cancer

Overseen By John Spittler, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Patrick Joseph Loehrer Sr.

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

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of three drugs to treat pancreatic cancer. It aims to find the best dose and see how safe and effective the treatment is for patients with this type of cancer. Gemcitabine has been a mainstay treatment for metastatic pancreatic cancer, often used in combination therapies to improve outcomes.

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.

What data supports the effectiveness of the drug combination Lonsurf, Gemcitabine, and Nab-Paclitaxel for pancreatic cancer?

Research shows that combining nab-paclitaxel (a form of paclitaxel) with gemcitabine significantly improves survival rates in patients with metastatic pancreatic cancer. This combination has been shown to prolong overall survival and progression-free survival compared to gemcitabine alone, making it a valuable treatment option for this type of cancer. ^{1 2 3 4 5}

Is the combination of Lonsurf and chemotherapy safe for treating pancreatic cancer?

The combination of nab-paclitaxel (Abraxane) and gemcitabine has been shown to be generally safe for treating pancreatic cancer, with common side effects like neutropenia (low white blood cell count) and peripheral neuropathy (nerve damage causing numbness or tingling). These side effects were usually manageable and reversible with dose adjustments. ^{1 2 4 5 6}

What makes the drug Lonsurf combined with chemotherapy unique for pancreatic cancer?

The combination of Lonsurf with chemotherapy drugs like gemcitabine and nab-paclitaxel is unique because it includes Lonsurf, which is not typically part of standard pancreatic cancer treatments. This combination may offer a new approach by potentially enhancing the effectiveness of existing chemotherapy regimens. ^{1 4 5 7 8}

Research Team

Patrick J Loehrer, MD

Principal Investigator

Indiana University

Eligibility Criteria

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.

≥ 18 years old at the time of informed consent

Ability to provide written informed consent and HIPAA authorization

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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 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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

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

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel: novel clinical and experimental evidence in pancreatic cancer. [2015]

4. Japan pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. [2022]

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

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

6. France 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. [2022]

7. England 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. [2022]

8. Japan 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). [2023]