Chemotherapy + Immunotherapy Before Surgery for Pancreatic Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Metastatic disease, Autoimmune disorders, 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

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

Compensation: Varies

Number of Visits: 4

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effects of gemcitabine, nab-paclitaxel, durvalumab, and oleclumab in treating patients with primary pancreatic cancer that may be able to be removed by surgery (resectable/borderline resectable). Chemotherapy drugs, such as gemcitabine and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as durvalumab and oleclumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving gemcitabine, nab-paclitaxel, durvalumab, and oleclumab may help control the disease in patients with resectable/borderline resectable primary pancreatic cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any other cancer treatments while participating in this study.

Is the combination of chemotherapy and immunotherapy safe for humans?

The combination of nanoparticle albumin-bound paclitaxel (Abraxane) and gemcitabine has been studied for safety in patients with pancreatic cancer, showing improved survival and tolerability. Additionally, durvalumab, an immunotherapy drug, has been evaluated for safety in combination with other treatments in patients with advanced cancers, indicating it is generally safe for human use. ^{1 2 3 4 5}

How is the drug combination of Durvalumab, Gemcitabine, Nab-paclitaxel, and Oleclumab unique for treating pancreatic cancer?

This drug combination is unique because it combines chemotherapy (Gemcitabine and Nab-paclitaxel) with immunotherapy (Durvalumab and Oleclumab) before surgery, aiming to enhance the body's immune response against cancer cells and improve surgical outcomes, which is not a standard approach for pancreatic cancer. ^{4 6 7 8 9}

Research Team

Brandon Smaglo, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with resectable or borderline resectable pancreatic adenocarcinoma who haven't had cancer treatment before. They must be able to follow the study plan, have good organ function, and a life expectancy of at least 6 months. Pregnant or breastfeeding individuals can't join, nor those with certain health conditions like autoimmune diseases, recent major surgery, or active infections.

Inclusion Criteria

Your hemoglobin level is at least 9.0 grams per deciliter.

I am fully active or restricted in physically strenuous activity but can do light work.

My pancreatic cancer is confirmed and considered operable.

Exclusion Criteria

I have had cancer spread to the lining of my brain and spinal cord.

I had a heart attack, mini-stroke, or stroke in the last 3 months.

I am not pregnant, breastfeeding, and if capable of having children, I agree to use birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive durvalumab, oleclumab, nab-paclitaxel, and gemcitabine intravenously. Treatment repeats every 28 days for 2-6 cycles.

8-24 weeks

Visits on days 1 and 15 of each cycle

Surgical Resection

Participants undergo surgical resection within 4-8 weeks after completion of the last cycle of treatment.

4-8 weeks

Adjuvant Therapy

Participants may receive adjuvant therapy with durvalumab and oleclumab, durvalumab, oleclumab, gemcitabine, and nab-paclitaxel, other chemotherapy, or observation only.

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 2 years

Follow-up every 3 months

Treatment Details

Interventions

• Durvalumab
• Gemcitabine
• Nab-paclitaxel
• Oleclumab

Trial Overview The trial tests if combining chemotherapy drugs (gemcitabine and nab-paclitaxel) with immunotherapy antibodies (durvalumab and oleclumab) before surgery can help treat pancreatic cancer. It's a phase II study to see how these treatments affect tumor growth by killing cells or boosting the immune system.

Participant Groups

Group I: Treatment (durvalumab, oleclumab, nab-paclitaxel, gemcitabine) Experimental Treatment 4 Interventions

Patients receive durvalumab IV over 1 hour on day 1, oleclumab IV over 1 hour, nab-paclitaxel IV, and gemcitabine IV over 1 hour over 30-40 minutes on days 1 and 15. Treatment repeats every 28 days for 2-6 cycles. Within 4-8 weeks after completion of last cycle of treatment, patients undergo surgical resection. After surgical resection, patient may receive adjuvant therapy with durvalumab and oleclumab, durvalumab, oleclumab, gemcitabine, and nab-paclitaxel, other chemotherapy, or observation only at the discretion of the treating physician.

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

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

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 MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

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]

In the NAPOLI 3 study involving 770 patients with metastatic pancreatic ductal adenocarcinoma, the NALIRIFOX treatment regimen resulted in a median overall survival of 11.1 months, which was significantly longer than the 9.2 months observed with the nab-paclitaxel and gemcitabine combination.

Both treatment groups experienced a high rate of grade 3 or higher adverse events (87% for NALIRIFOX and 86% for nab-paclitaxel-gemcitabine), indicating that while NALIRIFOX may improve survival, it does not significantly increase the risk of severe side effects compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Wainberg, ZA., Melisi, D., Macarulla, T., et al.[2023]

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]

In a study of 485 patients with localized pancreatic cancer, those treated with FOLFIRINOX showed higher rates of partial response according to RECIST criteria compared to those treated with gemcitabine plus nab-paclitaxel (GA), indicating better initial tumor response.

Despite the higher response rates and more frequent surgeries (pancreatectomy) in the FOLFIRINOX group, overall survival rates were similar between the two treatment regimens, suggesting that while FOLFIRINOX may be more effective in shrinking tumors, it does not necessarily lead to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Perri, G., Prakash, L., Qiao, W., et al.[2022]

The NEONAX trial is a large, phase II study involving 166 patients with resectable pancreatic ductal adenocarcinoma, comparing the efficacy of perioperative chemotherapy (nab-paclitaxel and gemcitabine) against standard adjuvant therapy to improve disease-free survival (DFS) at 18 months.

Preliminary evidence suggests that nab-paclitaxel/gemcitabine has a favorable toxicity profile compared to FOLFIRINOX, making it a promising option for patients undergoing surgery for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group. Ettrich, TJ., Berger, AW., Perkhofer, L., et al.[2022]

References

1. 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]

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

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. [2023]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. [2023]

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

First-Line Gemcitabine and Nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [2023]

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

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group. [2022]

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

The AGITG GAP Study: A Phase II Study of Perioperative Gemcitabine and Nab-Paclitaxel for Resectable Pancreas Cancer. [2022]