Nab-Paclitaxel + Gemcitabine +/- SBP-101 for Pancreatic Cancer

(ASPIRE Trial)

Recruiting at 101 trial locations

Overseen By Rachel Bragg, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Panbela Therapeutics, Inc.

Must be taking: Nab-paclitaxel, Gemcitabine

Must not be taking: Metformin, Hydroxychloroquine

Disqualifiers: BRCA mutations, Retinopathy, CNS metastasis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 100 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with metastatic pancreatic ductal adenocarcinoma, a type of pancreatic cancer that has spread. The researchers aim to determine if adding SBP-101, an experimental drug, to the standard treatment drugs nab-paclitaxel and gemcitabine (also known as Gemzar) improves outcomes. Eligible participants must have received a diagnosis of this cancer within the last three months and not yet undergone treatment for its spread. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking metformin (a diabetes medication) at least 5 days before starting the study and not use it during the trial. Other diabetic medications are allowed, but the protocol does not specify about other medications.

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

Research shows that SBP-101, when combined with nab-paclitaxel and gemcitabine, may help treat pancreatic cancer. A previous study found SBP-101 to be safe and tolerable for patients with advanced pancreatic cancer. Another study combining SBP-101 with nab-paclitaxel and gemcitabine also confirmed its safety.

Gemcitabine and nab-paclitaxel are well-known cancer treatments. They are generally well-tolerated, but like many treatments, they can cause side effects. These might include tiredness or low blood counts, but they are usually manageable.

In summary, current evidence suggests that using these treatments together is safe for people. However, always consult a doctor about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of SBP-101 with nab-paclitaxel and gemcitabine for pancreatic cancer because it introduces a novel component, SBP-101, which may enhance treatment effectiveness. Unlike the standard of care, which typically involves chemotherapy with drugs like gemcitabine and nab-paclitaxel, SBP-101 is believed to target the cancer cells more specifically. This could potentially improve outcomes by increasing the treatment's ability to attack cancer cells while minimizing damage to healthy cells. By adding SBP-101 to the existing regimen, researchers hope to increase survival rates and improve the quality of life for patients with this challenging condition.

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

Research shows that combining nab-paclitaxel and gemcitabine is a common treatment for pancreatic cancer. In this trial, participants in the experimental arm will receive SBP-101 in addition to nab-paclitaxel and gemcitabine. Studies suggest that adding SBP-101 might enhance the treatment's effectiveness. SBP-101 is designed to block certain processes in cancer cells, potentially stopping their growth. In early trials, adding SBP-101 to nab-paclitaxel and gemcitabine resulted in cancer shrinking or disappearing in 62% of patients. This promising outcome suggests that this combination could be more effective than the standard treatment alone for pancreatic cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Michael J Walker, MD

Principal Investigator

Panbela Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed metastatic pancreatic ductal adenocarcinoma who haven't been treated for it yet. They should be able to perform daily activities with ease or have only slight limitations (ECOG 0-1), and their major organs must function well. Pregnant women, those with certain genetic mutations (BRCA positive), severe diseases, recent major surgery, or a history of specific drug use are excluded.

Inclusion Criteria

My cancer can be measured on a scan.

I am fully active or can carry out light work.

I am not pregnant, can use birth control during the study, and if male, will also use contraception.

Exclusion Criteria

Participation in any other clinical investigation within 4 weeks of receiving the first dose of study drug.

I have taken hydroxychloroquine (Plaquenil) before.

I have a lung condition like interstitial lung disease or pulmonary fibrosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nab-paclitaxel and gemcitabine with or without SBP-101

Up to 100 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Nab-paclitaxel
• SBP-101

Trial Overview The study tests the effectiveness of SBP-101 added to standard chemotherapy drugs Nab-Paclitaxel and Gemcitabine in treating metastatic pancreatic cancer. Participants will either receive this combination or a placebo alongside the standard treatment in a randomized and double-blind setup.

How Is the Trial Designed?

Group I: Experimental Arm Experimental Treatment 3 Interventions

SBP-101 + Nab-paclitaxel and Gemcitabine

Group II: Control Arm Placebo Group 3 Interventions

Placebo + Nab-Paclitaxel and Gemcitabine

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?

Panbela Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

680+

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 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

Nab-paclitaxel, a new formulation of paclitaxel, has shown a good safety and efficacy profile for treating metastatic breast cancer (MBC), although there is limited data on its impact on overall survival.

In combination with gemcitabine, nab-paclitaxel significantly improves survival in advanced pancreatic cancer (PC) and demonstrates better results in non-small-cell lung cancer (NSCLC) patients with squamous histology, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. Cecco, S., Aliberti, M., Baldo, P., et al.[2015]

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]

Gemcitabine-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully developed and showed a favorable controlled release, with an encapsulation rate of approximately 83% and a particle size of about 150 nm.

In vivo studies demonstrated that Gem-HSA-NPs significantly inhibited tumor growth in pancreatic cancer while exhibiting lower toxicity compared to other treatment groups, indicating their potential as a safer and more effective delivery method for gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line. Yu, X., Di, Y., Xie, C., 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 study involving 221 patients with metastatic pancreatic ductal adenocarcinoma and poor performance status, the combination of NAB-paclitaxel and gemcitabine was found to be well tolerated, with manageable side effects such as anemia and neutropenia.

Both dosing regimens of NAB-paclitaxel (100 mg/m2 and 125 mg/m2) showed similar efficacy, with comparable response rates and median progression-free survival, indicating that this treatment is effective for fragile patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. Macarulla, T., Pazo-Cid, R., Guillén-Ponce, C., 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02657330

NCT02657330 | Study of SBP-101 in Pancreatic Cancer This first-in-human study of SBP-101 will be conducted in two phases: dose escalation and expansion. The dose escalation phase of the study is to evaluate the ...

2. clin.larvol.com clin.larvol.com/trial-detail/NCT03412799

Study of SBP-101 Combined With Nab-Paclitaxel and ... "Based on interim data from our Phase I trial, SBP-101 demonstrated a 62% objective response rate in combination with gemcitabine & abraxane (G&A); more than ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT282965

Efficacy of SBP-101, in combination with gemcitabine and ... Background: SBP-101, a polyamine metabolic inhibitor, inhibited growth in 6 human pancreatic ductal adenocarcinoma (PDA) cell lines and 3 murine xenograft ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.575

Efficacy of SBP-101, a polyamine metabolic inhibitor ... SBP-101 monotherapy in heavily pre-treated PDA patients (> 2 prior regimens) showed a median survival of 5.9 months at the optimal dose level.

5. targetedonc.com targetedonc.com/view/fda-lifts-partial-clinical-hold-from-study-of-sbp-101

FDA Lifts Partial Clinical Hold from Study of SBP-101 in ... Treatment with SBP-101 led to stable disease (SD) in 4 patients, 2 of whom were from cohort 3 and 2 from cohort 4. Four patents from cohort 5 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03412799

Study of SBP-101 Combined With Nab-Paclitaxel and ... This is an open-label phase 1A/1B study to assess the safety, tolerability and pharmacokinetics of SBP-101 when combined with nab-paclitaxel and gemcitabine.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12484532/

Efficacy and safety of the S-1, nab-paclitaxel, and gemcitabine ... The S-1/nab-paclitaxel/gemcitabine triplet regimen appears to improve survival outcomes while demonstrating potentially favorable tolerability ...