Ontegimod + Chemotherapy for Pancreatic Cancer

Overseen By Patrick Grierson, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Other malignancy, Brain metastases, Autoimmune, others

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

Compensation: Varies

Number of Visits: 2

61 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot use alternative, holistic, or botanical treatments for cancer, and you must not have had chemotherapy, small molecular therapy, or radiation therapy within 14 days before starting the trial.

What data supports the effectiveness of the drug combination Ontegimod, Gemcitabine, and Nab paclitaxel for pancreatic cancer?

Research shows that the combination of nab-paclitaxel and gemcitabine improves survival rates and tumor response in patients with advanced pancreatic cancer compared to gemcitabine alone. ^{1 2 3 4 5}

Is the combination of Ontegimod, Gemcitabine, and Nab-paclitaxel safe for humans?

The combination of nab-paclitaxel and gemcitabine has been studied in various trials and generally shows an acceptable safety profile in patients with advanced solid tumors, including pancreatic cancer. ^{5 6 7 8 9}

How is the Ontegimod + Chemotherapy drug different for pancreatic cancer?

The Ontegimod + Chemotherapy treatment for pancreatic cancer is unique because it combines Ontegimod with gemcitabine and nab-paclitaxel, which have shown improved survival rates over gemcitabine alone. This combination may offer a novel approach by potentially enhancing the effects of chemotherapy through Ontegimod's mechanism, although specific details about Ontegimod's role are not provided in the research. ^{1 4 5 10 11}

What is the purpose of this trial?

The investigators hypothesize that CD11b agonism reprograms the tumor microenvironment (TME) to overcome resistance to checkpoint immunotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, the investigators propose an open label phase I/II clinical trial of Ontegimod with gemcitabine and nab-paclitaxel in unresectable pancreatic ductal adenocarcinoma prior to future studies incorporating anti-PD1 checkpoint immunotherapy.

Research Team

Patrick Grierson, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for individuals with metastatic pancreatic ductal adenocarcinoma who have already tried one treatment without success. Participants should be able to perform daily activities with minimal assistance. Specific eligibility details are not provided, but typically include factors like age, overall health, and cancer stage.

Inclusion Criteria

My doctor can safely take a biopsy of my cancer for research.

I've had treatment for advanced pancreatic cancer that didn't work or caused side effects.

I can understand and am willing to sign the consent form, or have someone legally authorized to do so on my behalf.

Exclusion Criteria

I have not had major surgery within the last 28 days.

I have a stomach condition that affects medication absorption.

I have severe nerve pain or numbness.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Ontegimod with gemcitabine and nab-paclitaxel administered in 28-day cycles to determine the maximum tolerated dose

12 months

Visits on Days 1, 8, and 15 of each 28-day cycle

Phase II Treatment

Ontegimod with gemcitabine and nab-paclitaxel administered in 28-day cycles at the recommended phase II dose

6 months

Visits on Days 1, 8, and 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• Gemcitabine
• Nab paclitaxel
• Ontegimod

Trial Overview The study tests Ontegimod combined with chemotherapy drugs Gemcitabine and Nab-paclitaxel as a second-line treatment for pancreatic cancer. It's an early-phase trial aiming to see if this combination can make the body's environment less friendly to cancer and improve outcomes.

Participant Groups

Group I: Phase I Dose de-escalation (starting dose): Ontegimod + Gemcitabine + Nab-paclitaxel Experimental Treatment 3 Interventions

Ontegimod is an oral medication taken twice daily on Days 1-21 of each 28-day cycle. The starting dose is 800 mg. Gemcitabine and nab-paclitaxel will be given as per standard of care (intravenous on Days 1, 8, and 15 of each 28-day cycle).

Group II: Phase 2 Experimental Arm: Ontegimod + Gemcitabine + Nab-paclitaxel Experimental Treatment 3 Interventions

Ontegimod is an oral medication taken twice daily on Days 1-21 of each 28-day cycle. The dose will determined during the Phase I portion of the trial. Gemcitabine and nab-paclitaxel will be given as per standard of care (intravenous on Days 1, 8, and 15 of each 28-day cycle).

Group III: Phase 2 Control Arm: Gemcitabine + Nab-paclitaxel Active Control 2 Interventions

Gemcitabine and nab-paclitaxel will be given as per standard of care (intravenous on Days 1, 8, and 15 of each 28-day cycle).

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of patients with resected pancreatic ductal adenocarcinoma (PDAC), adjuvant chemotherapy with nab-paclitaxel plus gemcitabine (AG) significantly improved median disease-free survival (15.8 months) and overall survival (28.3 months) compared to gemcitabine alone (12.2 months and 20.6 months, respectively).

While AG showed better survival outcomes, it also led to a higher incidence of sensory neuropathy (53.3% in AG vs. 23.3% in GEM), indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. Yin, ZZ., Zhao, ZM., Tang, WB., et al.[2020]

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., 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 phase I/II study involving 34 Japanese patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine demonstrated a high objective response rate of 58.8%, indicating promising efficacy for this treatment regimen.

The treatment was associated with manageable safety, with the most common severe adverse effects being neutropenia (70.6%) and leukopenia (55.9%), but no treatment-related deaths were reported, suggesting that the regimen can be safely administered with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Ueno, H., Ikeda, M., Ueno, M., et al.[2022]

In a study involving 866 patients with resected pancreatic ductal adenocarcinoma, the combination of nab-paclitaxel and gemcitabine showed a significant improvement in overall survival (OS) compared to gemcitabine alone, with a median OS of 41.8 months versus 37.7 months, respectively.

Although the primary endpoint of disease-free survival (DFS) was not significantly improved with nab-paclitaxel + gemcitabine, the treatment was associated with a higher incidence of grade ≥ 3 adverse events (86% vs. 68% for gemcitabine), indicating a need for careful consideration of safety alongside efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. Tempero, MA., Pelzer, U., O'Reilly, EM., et al.[2023]

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]

In a review of seven randomized controlled trials involving 1544 patients, adding a targeted agent to the gemcitabine plus nab-paclitaxel (GA) regimen did not significantly improve overall survival (OS) or progression-free survival (PFS) compared to GA alone.

While the addition of a targeted agent did not enhance efficacy, it was associated with a higher incidence of grade 3/4 diarrhea, indicating that the combination may increase toxicity without providing additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of gemcitabine plus nab-paclitaxel combined with targeted agents in the treatment of metastatic pancreatic cancer. Li, ZH., Ma, YJ., Jia, ZH., 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]

References

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

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. [2020]

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

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]

3. Greece pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. [2022]

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

Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. [2022]

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

Prognostic factors for survival with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer in real-life practice: the ANICE-PaC study. [2022]

6. 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]

7. Germany pubmed.ncbi.nlm.nih.gov

Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. [2022]

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

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. [2023]

9. 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]

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

Meta-analysis of gemcitabine plus nab-paclitaxel combined with targeted agents in the treatment of metastatic pancreatic cancer. [2022]

11. 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]