Onvansertib + NALIRIFOX for Pancreatic Cancer

(PANCONVA Trial)

Overseen By KUCC Navigation

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Kansas Medical Center

Must not be taking: QT prolonging, CYP3A4 inhibitors

Disqualifiers: Pregnancy, Brain metastasis, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 2 years

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find better treatment options for pancreatic cancer, particularly for patients with a mutation in the KRAS gene, which is common in these tumors. The study tests a new drug, onvansertib, in combination with an existing treatment called NALIRIFOX (a chemotherapy regimen), to determine if it can improve outcomes for those with advanced pancreatic cancer. Individuals diagnosed with pancreatic cancer that has spread or cannot be surgically removed, and who have not yet received treatment for this stage of their disease, might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires stopping certain medications that affect heart rhythm or interact with the study drug. If you're on these, you may need to switch to alternatives or stop them 1-2 weeks before starting the trial. Check with the trial team for specific guidance.

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

Research has shown that NALIRIFOX, part of the treatment under study, can extend life without worsening quality of life, indicating it is generally well-tolerated by patients.

Onvansertib is a newer treatment still under investigation, so less is known about its safety. However, its presence in early-stage trials indicates it has passed initial safety checks. To date, no major safety issues have emerged, but further research is necessary to fully understand its safety in humans.

Joining this trial could contribute to researchers' understanding of the safety and effectiveness of this treatment combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Onvansertib for pancreatic cancer because it targets the PLK1 enzyme, which plays a crucial role in cancer cell division. Unlike standard treatments like FOLFIRINOX, Onvansertib is taken orally, making it more convenient for patients. Additionally, when combined with NALIRIFOX, it may enhance the effectiveness of chemotherapy by specifically disrupting cancer cells' ability to multiply, potentially improving outcomes for patients with this challenging condition.

What evidence suggests that Onvansertib + NALIRIFOX could be an effective treatment for pancreatic cancer?

Studies have shown that NALIRIFOX, a treatment for pancreatic cancer, extends patient survival compared to the older gemcitabine-based therapy. Patients using NALIRIFOX live an average of 11.1 months, while those using only gemcitabine live about 6.7 months. In this trial, participants will receive a combination of NALIRIFOX and Onvansertib. Onvansertib, a new component of this treatment, targets a protein called PLK1, which aids cancer cell growth. Early research suggests that Onvansertib can enhance the treatment's cancer-fighting ability, as demonstrated in lab studies. This combination could offer a new option for patients with pancreatic cancer, particularly those with changes in the KRAS gene, where effective treatments are currently limited. ^{1 2 3 4 6}

Who Is on the Research Team?

Anup Kasi, MD, MPH

Principal Investigator

The University of Kansas Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults (18+) with advanced pancreatic cancer that hasn't spread and who haven't had treatment yet. They need to be able to understand the study, agree in writing, and have measurable disease by RECIST 1.1 standards. Participants must also provide tissue samples and have a good performance status (ECOG 0/1), along with specific blood cell count levels.

Inclusion Criteria

My cancer can be measured using standard imaging techniques.

I understand the study and agree to sign the consent form.

My cancer is a type of pancreatic cancer confirmed by lab tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Onvansertib orally daily on D1-5 of each 14-day cycle and NALIRIFOX intravenously on D1 of each 14-day cycle

Approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NALIRIFOX
• Onvansertib

Trial Overview The trial tests Onvansertib, an oral drug targeting PLK1 proteins involved in tumor growth, combined with NALIRIFOX therapy. It aims to improve survival rates for patients with KRAS-mutated pancreatic cancer where current treatments are limited.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

Study Drug: Onvansertib: Orally daily on D1 - 5 of each 14-day cycle NALIRIFOX Intravenous D1 of each 14-day cycle

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Cardiff Oncology

Industry Sponsor

Trials

12

Recruited

650+

Published Research Related to This Trial

In a phase II trial involving 17 patients with advanced pancreatic cancer, the combination of sorafenib and gemcitabine showed no objective responses, with only 18% of patients achieving stable disease.

The treatment resulted in a median overall survival of 4.0 months and was associated with significant toxicities, including thrombosis in 18% of patients, indicating that this combination is not effective for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. Kindler, HL., Wroblewski, K., Wallace, JA., et al.[2022]

The introduction of newer chemotherapy regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel, led to a significant improvement in overall survival for patients with metastatic pancreatic cancer, with median survival increasing from 8.97 months to 9.95 months between the years 2006-2010 and 2011-2015.

Despite the overall improvement in survival rates, African American patients experienced worse outcomes, indicating a disparity in treatment effectiveness, with a hazard ratio of 1.63 for death compared to Caucasian patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma With the Introduction of New Chemotherapeutic Drugs: 10-Year Experience of a Single NCI-designated Comprehensive Cancer Center. Zhang, KJ., Dyson, G., Gatz, JL., et al.[2019]

The combination of APX005M (sotigalimab) with gemcitabine and nab-paclitaxel, with or without nivolumab, was found to be tolerable in patients with metastatic pancreatic adenocarcinoma, with a recommended phase 2 dose of 0.3 mg/kg for APX005M established during the study.

Clinical activity was observed, with 58% of patients showing responses, suggesting that this treatment regimen could potentially replace the current chemotherapy-only standard of care for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. O'Hara, MH., O'Reilly, EM., Varadhachary, G., 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]

In a study of 76 patients with metastatic pancreatic cancer, mFOLFIRINOX treatment resulted in significantly better objective response rates (20.0% vs 0%) and progression-free survival (3.7 months vs 2.1 months) compared to the oral fluoropyrimidine S-1.

While mFOLFIRINOX showed promising treatment outcomes, it also led to more frequent severe side effects, such as grade 3-4 neutropenia and peripheral sensory neuropathy, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with S-1 as second-line chemotherapy in metastatic pancreatic cancer. Ikezawa, K., Kiyota, R., Takada, R., et al.[2022]

The combination of cediranib and olaparib did not show clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not have a known BRCA mutation, as no objective responses were observed in the study of 19 patients.

Despite some patients experiencing stable disease for a median of 3.1 months, the overall survival was only 3.4 months, indicating limited efficacy of this treatment combination in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. Kim, JW., Cardin, DB., Vaishampayan, UN., et al.[2022]

A combination of gemcitabine and erlotinib has been shown to provide a survival advantage in patients with locally advanced and metastatic pancreatic cancer compared to gemcitabine alone, highlighting its efficacy in a disease known for poor outcomes.

Erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor, demonstrates anti-tumor activity when used alongside gemcitabine, suggesting a promising mechanism of action in treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of erlotinib in the management of pancreatic cancer. Starling, N., Neoptolemos, J., Cunningham, D.[2021]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06736717?term=AREA%5BInterventionSearch%5D(PCM-075)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=4

Study Details | NCT06736717 | Onvansertib in ... All three combinations have shown a survival advantage over previously standard gemcitabine-based therapy, with 11.1 months overall survival (OS) for NALIRIFOX/ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12345255/

Health-related quality of life and performance status with ... Taken together with the results of the NAPOLI 3 trial, these data suggest that 1L NALIRIFOX provides efficacy benefits without compromising ...

3. withpower.com withpower.com/trial/onvansertib-nalirifox-for-pancreatic-cancer-ca1e2

Onvansertib + NALIRIFOX for Pancreatic Cancer All three combinations have shown a survival advantage over previously standard gemcitabine-based therapy, with 11.1 months overall survival (OS) for NALIRIFOX/ ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/562756

Onvansertib in Combination With NALIRIFOX for First Line ... All three combinations have shown a survival advantage over previously standard gemcitabine-based therapy, with 11.1 months overall survival (OS) for NALIRIFOX/ ...

5. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/study00161071

A Phase Ib/II trial of Onvansertib in Combination with ... A Phase Ib/II trial of Onvansertib in Combination with NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer

6. npcf.us npcf.us/clinical-trials/onvansertib-in-combination-with-nalirifox-for-first-line-treatment-of-advanced-pancreatic-cancer/

Onvansertib In Combination With NALIRIFOX For First Line ... All three combinations have shown a survival advantage over previously standard gemcitabine-based therapy, with 11.1 months overall survival (OS) for NALIRIFOX/ ...