Ontegimod + Chemotherapy for Pancreatic Cancer

Not yet recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new treatment combination can improve outcomes for individuals with pancreatic cancer that cannot be surgically removed. The trial tests Ontegimod, an oral medication, alongside two standard chemotherapy drugs, gemcitabine and nab-paclitaxel. Researchers believe this combination might alter the cancer environment in the body, enhancing the effectiveness of future immunotherapy. Suitable candidates have pancreatic cancer that has worsened despite first-line treatment and seek another treatment option. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of gemcitabine and nab-paclitaxel is generally well-tolerated by people with pancreatic cancer. Studies indicate that this combination is effective and safe, even outside controlled settings. For instance, one study found that patients using these two drugs lived longer than those using only gemcitabine.

Ontegimod, the new drug tested in this trial, remains in the early stages of research. Limited information exists about its safety, but its inclusion in a clinical trial suggests it has shown enough potential for further study. This trial will assess how well patients tolerate Ontegimod when used with the other two drugs.

In summary, while gemcitabine and nab-paclitaxel are known to be safe for treating pancreatic cancer, Ontegimod is new and still under investigation. Early trials like this one are essential for learning about its safety in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Ontegimod because it introduces a novel approach to treating pancreatic cancer by working alongside standard chemotherapy drugs, gemcitabine and nab-paclitaxel. Ontegimod is an oral medication that is easy to take and is designed to be administered twice daily, which could enhance patient convenience. Unlike existing treatments that often focus solely on chemotherapy, Ontegimod may offer a new mechanism of action that works synergistically with standard care, potentially improving treatment effectiveness and outcomes for patients with pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that combining gemcitabine with nab-paclitaxel extends survival in people with pancreatic cancer. One study found that patients lived about 13.87 months with this combination, compared to 8.5 months with gemcitabine alone. In this trial, Ontegimod is being tested alongside these treatments in the experimental arms. Researchers believe it alters the tumor environment to enhance the immune system's ability to fight cancer. Early signs suggest it might increase treatment effectiveness, but further research is needed for confirmation. ^{3 6 7 8 9}

Who Is on the Research Team?

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

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06904378

Ontegimod and Gemcitabine/Nab-paclitaxel as Second ... Therefore, the investigators propose an open label phase I/II clinical trial of Ontegimod with gemcitabine and nab-paclitaxel in unresectable pancreatic ductal ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36181099/

The effectiveness of nab-paclitaxel plus gemcitabine and ... Nab-P/Gem resulted in OS of 13.87 months compared to 8.5 months in patients receiving Gem. The same trend was achieved in PFS, 5.37 versus 2.80 ...

3. clinconnect.io clinconnect.io/trials/NCT06904378

Ontegimod and Gemcitabine/Nab-paclitaxel as Second Line This clinical trial is studying a new treatment approach for patients with advanced pancreatic cancer that cannot be surgically removed. Researchers want to see ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-018-5244-2

Real world evidence on gemcitabine and nab-paclitaxel ... In the recent phase III trial MPACT the combination of gemcitabine and nab-paclitaxel (Gem/NabP) showed increased overall survival compared to ...

5. cancer.gov cancer.gov/types/pancreatic/research/nab-paclitaxel-gemcitabine

Nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic ... Patients who received the drug combination had a median overall survival of 8.5 months, compared with 6.7 months for patients treated with gemcitabine alone.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06904378

Ontegimod and Gemcitabine/Nab-paclitaxel as Second ... Therefore, the investigators propose an open label phase I/II clinical trial of Ontegimod with gemcitabine and nab-paclitaxel in unresectable pancreatic ductal ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32957885/

Clinical Outcomes and Safety of Patients Treated with NAb ... Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24131140/

Increased survival in pancreatic cancer with nab-paclitaxel ... The survival rate was 35% in the nab-paclitaxel-gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years.

9. mdpi.com mdpi.com/2072-6694/17/17/2821

Real-World Evidence of the Efficacy and Safety of Second ... The aim of this clinical study was a retrospective analysis of the medical history of 109 patients with metastatic pancreatic cancer (mPC).