Nab-Paclitaxel + Nivolumab for Pancreatic Cancer

Overseen By Douglas R. Adkins

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Systemic corticosteroids, Taxanes

Disqualifiers: Active CNS metastases, Autoimmune disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

46 Participants Needed

Trial Summary

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 systemic corticosteroid therapy at doses higher than 10 mg of prednisone equivalent daily, you may need to stop or adjust it before starting the trial.

What data supports the effectiveness of the drug nab-paclitaxel (Abraxane) for pancreatic cancer?

Research shows that nab-paclitaxel, when combined with gemcitabine, improved response rates and survival times in patients with advanced pancreatic cancer compared to gemcitabine alone. Specifically, the combination increased the response rate from 7% to 23% and extended overall survival from 6.7 months to 8.5 months. ^{1 2 3 4 5}

Is the combination of Nab-Paclitaxel and Nivolumab safe for treating pancreatic cancer?

The combination of Nab-Paclitaxel and Nivolumab, when used with gemcitabine for advanced pancreatic cancer, has shown a manageable safety profile. Common side effects include neutropenia (low white blood cell count) and peripheral neuropathy (nerve damage), which were generally reversible with dose adjustments. ^{2 3 6 7 8}

How is the drug combination of nab-paclitaxel and nivolumab unique for treating pancreatic cancer?

The combination of nab-paclitaxel and nivolumab for pancreatic cancer is unique because nab-paclitaxel is an albumin-bound form of paclitaxel that improves drug delivery and reduces side effects, while nivolumab is an immunotherapy that helps the immune system attack cancer cells. This combination aims to enhance treatment effectiveness by combining chemotherapy with immunotherapy. ^{1 3 4 7 8}

What is the purpose of this trial?

The primary hypothesis is that the objective response rate (ORR) with nab-paclitaxel and nivolumab will be significantly higher than the historical control (ORR 30%). The KEY secondary hypothesis is that the median PFS with nab-paclitaxel and nivolumab will be significantly longer than the historical control (median PFS 3.6 months).

Research Team

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Adults with recurrent or metastatic head and neck squamous-cell carcinoma that worsened after PD-1/PD-L1 inhibitor therapy. They must be in good physical condition, have normal organ and bone marrow function, not be pregnant or breastfeeding, agree to use contraception, and have no history of severe allergies to similar drugs or serious autoimmune diseases.

Inclusion Criteria

AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (in cases of bone mets or liver mets, AST/ALT < 5 x IULN)

Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable) before the performance of any protocol-related procedures.

My kidney function is within the normal range.

Exclusion Criteria

A history of serious allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study (Allergic reaction to cetuximab is allowed as there are other standard of care options for the investigator's choice arm)

Prisoners, or subjects who are compulsory detained

I had cancer before, but I finished treatment over a year ago and am now cancer-free.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nab-Paclitaxel 125 mg/m^2 IV on days 1, 8 & 15 and Nivolumab 480 mg IV on day 1 of each 28-day cycle

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

13 months

Treatment Details

Interventions

• nab-paclitaxel
• Nivolumab

Trial Overview The trial is testing the effectiveness of combining nab-paclitaxel with nivolumab against this type of cancer. The goal is to see if this combination improves response rates and progression-free survival compared to past results from other treatments.

Participant Groups

Group I: nab-Paclitaxel + Nivolumab Experimental Treatment 2 Interventions

* nab-Paclitaxel 125 mg/m\^2 intravenous (IV) on days 1, 8 \& 15 of each 28-day cycle. * Nivolumab 480 mg IV Day 1 of each 28-day cycle.

nab-paclitaxel is already approved in United States, European Union for the following indications:

Approved in United States as Abraxane for:

• Metastatic pancreatic adenocarcinoma

Approved in European Union as Abraxane for:

• Metastatic pancreatic adenocarcinoma

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

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 of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., 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 large Phase III clinical trial, the combination of nab-paclitaxel and gemcitabine significantly improved treatment outcomes for advanced pancreatic adenocarcinoma, increasing the response rate from 7% to 23%.

Patients receiving the combination therapy also experienced longer progression-free survival (5.5 months compared to 3.7 months) and overall survival (8.5 months compared to 6.7 months) compared to those treated with gemcitabine alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel: potential for the treatment of advanced pancreatic cancer. Al-Hajeili, M., Azmi, AS., Choi, M.[2021]

The combination of nab-paclitaxel (Abraxane) and the fusion protein hIL15-ABD significantly reduced tumor size by 40%-60% in murine models of pancreatic ductal adenocarcinoma (PDAC), indicating enhanced efficacy compared to vehicle treatment.

This combination therapy increased the presence of active immune cells, such as CD8+ T cells and M1 macrophages, while reducing immunosuppressive cells in the tumor microenvironment, suggesting a mechanism that enhances anticancer immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic effect of Abraxane that combines human IL15 fused with an albumin-binding domain on murine models of pancreatic ductal adenocarcinoma. Hsu, FT., Tsai, CL., Chiang, IT., et al.[2022]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

In a phase I trial involving 50 patients with advanced pancreatic cancer, the combination of nivolumab, nab-paclitaxel, and gemcitabine showed a manageable safety profile, with 48 patients experiencing grade 3/4 treatment-emergent adverse events, but only one dose-limiting toxicity reported.

The treatment resulted in a median overall survival of 9.9 months and an overall response rate of 18%, indicating limited efficacy, which led to the conclusion that further investigation of this combination is not supported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. Wainberg, ZA., Hochster, HS., Kim, EJ., 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]

References

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

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

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

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

3. 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]

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

Nab-paclitaxel: potential for the treatment of advanced pancreatic cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Synergistic effect of Abraxane that combines human IL15 fused with an albumin-binding domain on murine models of pancreatic ductal adenocarcinoma. [2022]

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

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). [2022]

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

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. [2022]

8. 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]