Combination Therapy for Pancreatic Cancer

Recruiting at 2 trial locations

Overseen By Study Listserv

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NYU Langone Health

Must not be taking: Immunotherapy, IL-1 inhibitors

Disqualifiers: Neuroendocrine carcinoma, Metastatic disease, Autoimmune disease, Cardiac disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to determine their safety and effectiveness for individuals with pancreatic cancer confined to the pancreas. The study evaluates how well two immunotherapy drugs, canakinumab (Ilaris) and tislelizumab, work with standard chemotherapy—gemcitabine (Gemzar) and nab-paclitaxel (Abraxane)—to shrink tumors before surgery. It aims to identify the optimal dose and assess whether the treatment facilitates or increases the likelihood of surgery. Individuals diagnosed with pancreatic cancer that remains localized and who have not undergone other treatments may be suitable candidates for this trial. Participants will undergo regular check-ups, scans, and receive the treatment over four months. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications for active autoimmune diseases or have received certain immunotherapies, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of nab-paclitaxel and gemcitabine is generally well-tolerated by patients with advanced pancreatic cancer. Previous studies indicate that most people can handle this chemotherapy duo without severe side effects.

The addition of canakinumab and tislelizumab to this treatment is still under investigation. These drugs aim to enhance the immune system's ability to fight cancer. As this is a Phase 1 trial, researchers are closely monitoring the safety of these combinations. Early trials like this help identify potential side effects and their frequency.

For those considering joining a trial, it's important to know that while the drugs have shown promise, researchers are still confirming their safety. Always discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination therapy for pancreatic cancer because it brings together a mix of innovative approaches that differ from the standard treatments like FOLFIRINOX or gemcitabine with nab-paclitaxel. This treatment combines canakinumab, an anti-inflammatory drug, and tislelizumab, an immune checkpoint inhibitor, which potentially enhances the body's own immune response against cancer. By adding these to the traditional chemotherapy duo of nab-paclitaxel and gemcitabine, this regimen aims to attack the cancer on multiple fronts. This combination could lead to improved outcomes by both directly targeting the cancer cells and empowering the immune system to recognize and destroy them more effectively.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

This trial will evaluate a combination therapy for pancreatic cancer, consisting of canakinumab, tislelizumab, nab-paclitaxel, and gemcitabine. Research has shown that combining these drugs might improve treatment outcomes for pancreatic cancer patients. Tislelizumab enhances the immune system's ability to attack cancer cells, while canakinumab reduces inflammation, potentially boosting the overall effectiveness of this treatment mix. Previous studies found that using tislelizumab with nab-paclitaxel and gemcitabine effectively treats recurrent pancreatic cancer. This combination aims to make the tumor more manageable and increase the chances of successful surgery. ^{1 4 5 6 7}

Who Is on the Research Team?

Paul Oberstein, MD

Principal Investigator

Perlmutter New York University Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed pancreatic ductal adenocarcinoma who haven't had cancer treatment before. They should be in good health overall, able to follow the study schedule, and willing to use contraception. It's not for those with certain other cancers, advanced or metastatic disease, previous immunotherapy for pancreatic cancer, immune system issues, significant medical risks, known allergies to study drugs or their ingredients.

Inclusion Criteria

I have not had any cancer treatment for pancreatic cancer.

My cancer is confirmed to be pancreatic ductal adenocarcinoma.

I am using two birth control methods or am not having sex to avoid pregnancy during and 9 months after the study.

Exclusion Criteria

History of known hypersensitivity to any of the drugs used in this study or any of their excipients

I have never taken canakinumab or similar drugs.

I have an autoimmune disease treated with medication in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Canakinumab and Tislelizumab in combination with Nab-Paclitaxel and Gemcitabine for up to 4 cycles

16 weeks

Regular visits for labs and CT scans

Surgical Evaluation

Assessment of eligibility for surgical resection based on treatment response

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 months post treatment

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab
• Gemcitabine
• Nab-Paclitaxel
• Tislelizumab

Trial Overview The trial tests a combination of Canakinumab and Tislelizumab with Nab-Paclitaxel and Gemcitabine as pre-surgery (neo-adjuvant) treatment for pancreatic cancer. The aim is to find safe doses of this four-drug regimen and see if it helps patients proceed to surgery while assessing its preliminary effects on tumors.

How Is the Trial Designed?

Group I: Quadruplet regimen prior to resection for pancreatic cancer Experimental Treatment 4 Interventions

Treatment of Canakinumab and Tislelizumab in Combination with Nab-Paclitaxel and Gemcitabine up to 4 cycles (4 months)

Canakinumab is already approved in European Union, United States for the following indications:

Approved in European Union as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Approved in United States as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

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]

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., 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]

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]

The recent phase III MPACT trial demonstrated that nab-paclitaxel, when added to gemcitabine, significantly improved survival rates in patients with metastatic pancreatic cancer, indicating its efficacy in a previously challenging area.

The success of nab-paclitaxel highlights the importance of innovative drug delivery technologies, such as albumin nanoparticle formulations, in enhancing the effectiveness of anticancer therapies while minimizing toxicities associated with traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The winning formulation: the development of paclitaxel in pancreatic cancer. Ma, WW., Hidalgo, M.[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]

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 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/NCT05984602

NCT05984602 | A Phase IB Study to Determine the Safety ... Determine the safety and tolerability of canakimumab in combination with tislelizumab, nab-paclitaxel and gemcitabine; Assess the preliminary clinical anti ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05651

Canakinumab and Tislelizumab in Combination with Nab ... Giving canakinumab and tislelizumab in combination with nab-paclitaxel and gemcitabine may work better in treating patients with resectable pancreatic cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04902261

Tislelizumab Combined With Nab-paclitaxel and ... To evaluate the efficacy of Tislelizumab combined with Nab-paclitaxel and Gemcitabine in the treatment of recurrent pancreatic cancer.

4. withpower.com withpower.com/trial/phase-1-pancreatic-neoplasms-6-2023-0b3a3

Combination Therapy for Pancreatic Cancer Canakinumab is an anti-inflammatory drug, and Tislelizumab is an immune checkpoint inhibitor, both of which may enhance the effectiveness of the chemotherapy ...

5. clinconnect.io clinconnect.io/trials/NCT04902261

Tislelizumab Combined With Nab-paclitaxel and - ClinConnect To evaluate the efficacy of Tislelizumab combined with Nab-paclitaxel and Gemcitabine in the treatment of recurrent pancreatic cancer.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/417077

A Phase IB Study to Determine the Safety and Tolerability ... A Phase IB Study to Determine the Safety and Tolerability of Canakinumab and Tislelizumab in Combination With Nab-Paclitaxel and Gemcitabine in ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT05984602

A Phase IB Study to Determine the Safety and Tolerability ... The surgical team will review whether there are any delays in outcome in surgery that is attributed to study drug. At surgery post treatment (up until 6 months).