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

Trial Summary

What is the purpose of this trial?

The goal of this Single Arm Phase Ib clinical trial is to test standard of care chemotherapy and anti PD1 and IL1b to evaluate the safety and preliminary toxicity of this quadruplet regimen prior to resection in patients with pancreatic cancer. The main objectives it aims to answer are to: * Determine the recommended Phase II dose regimen of canakinumab and tislelizumab in combination with gemcitabine and nab-paclitaxel in patients with localized pancreatic ductal adenocarcinoma. * Estimate the proportion of patients who proceed to surgical resection. * Determine the safety and tolerability of canakimumab in combination with tislelizumab, nab-paclitaxel and gemcitabine * Assess the preliminary clinical anti-tumor activity of canakimumab in combination with tislelizumab, nab-paclitaxel and gemcitabine * Assess whether therapy has any impact on surgical options Participants will have labs drawn, CT scans, and a treatment administered consisting of: * Gemcitabine * Nab-paclitaxel * Canakinumab * Tislelizumab

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.

What data supports the effectiveness of the drug combination therapy for pancreatic cancer?

Research shows that combining nab-paclitaxel (a form of paclitaxel) with gemcitabine significantly improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. This combination has shown substantial clinical activity and is considered effective in treating metastatic pancreatic cancer. ^{1 2 3 4 5}

Is the combination therapy for pancreatic cancer safe for humans?

The combination of nab-paclitaxel (a type of chemotherapy) and gemcitabine has been shown to have an acceptable safety profile in patients with advanced pancreatic cancer, including elderly patients. This means it is generally considered safe for use in humans, although individual reactions can vary. ^{1 2 3 6 7}

What makes the combination therapy for pancreatic cancer unique?

This combination therapy for pancreatic cancer is unique because it includes Canakinumab and Tislelizumab, which are not typically used in standard treatments. Canakinumab is an anti-inflammatory drug, and Tislelizumab is an immune checkpoint inhibitor, both of which may enhance the effectiveness of the chemotherapy drugs Gemcitabine and Nab-Paclitaxel by targeting the cancer in different ways. ^{1 2 3 4 8}

Research Team

Paul Oberstein, MD

Principal Investigator

Perlmutter New York University Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

3. United States 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. [2022]

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

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

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

The winning formulation: the development of paclitaxel in pancreatic cancer. [2022]

6. Japan 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. [2022]

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

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

8. Japan pubmed.ncbi.nlm.nih.gov

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