CEND-1 + FOLFIRINOX for Digestive Cancer

(CENDIFOX Trial)

Not currently recruiting at 2 trial locations

Overseen By KUCC Navigation

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Anup Kasi

Must be taking: Folfirinox, Panitumumab

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: Pregnancy, Cardiac disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment combination for certain digestive cancers, such as pancreatic, colon, and appendix cancer. The study examines how well the drug CEND-1 works with Folfirinox (a chemotherapy regimen), and sometimes with Panitumumab, to address these challenging cancers. Suitable candidates for this trial include those with specific types of these cancers that are potentially removable through surgery and have not received other cancer treatments in the last two years. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any other anti-cancer therapy while participating. It's best to discuss your current medications with the trial team.

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

Research shows that combining CEND-1 with FOLFIRINOX is generally well-tolerated by patients with certain types of cancer. Studies found that adding CEND-1 to FOLFIRINOX is safe for patients with a type of pancreatic cancer. These early results showed that patients could handle the treatment without major problems.

Similarly, research indicates that combining FOLFIRINOX with Panitumumab is also generally safe. This combination has been used in patients with colorectal cancer who have specific gene types (RAS/BRAF wild type) and did not cause unexpected side effects.

In summary, both treatment combinations have been tested and are considered safe based on current data. Participants who met the study criteria managed the treatments without severe side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CEND-1 combined with FOLFIRINOX because it offers a novel approach to treating digestive cancers, particularly pancreatic and colon cancers. Unlike the current standard of care, which often involves chemotherapy alone, this combination introduces CEND-1, a peptide that enhances the uptake of chemotherapy drugs by targeting the tumor's microenvironment. This unique mechanism aims to improve the effectiveness of FOLFIRINOX, potentially leading to better outcomes for patients. Additionally, when paired with Panitumumab in certain cases, this treatment could offer a more personalized approach, especially for patients with specific genetic profiles like RAS/BRAF mutations.

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

Research has shown that combining CEND-1 with FOLFIRINOX may hold promise for treating certain digestive cancers. In this trial, participants in Cohort 1 will receive FOLFIRINOX, followed by FOLFIRINOX plus CEND-1, for pancreatic cancer. Studies have found this combination to be safe for patients with pancreatic cancer, with many experiencing ongoing benefits. Earlier trials reported a 26% success rate for FOLFIRINOX alone in treating advanced pancreatic cancer, with some patients achieving complete recovery.

For participants in Cohorts 2 and 3, the combination of FOLFIRINOX and Panitumumab, with or without CEND-1, is being tested for peritoneal metastases and oligometastatic colon cancer. Research has shown high success rates for FOLFIRINOX and Panitumumab, though it did not achieve all primary goals in some colorectal cancer cases. However, it was effective enough in some patients to shrink tumors for surgical removal. These findings suggest that these combinations could be effective against digestive cancers, but further research is needed to fully understand their potential. ^{1 2 3 5 6}

Who Is on the Research Team?

Anup Kasi, MD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with certain types of cancer (pancreatic, colon, or appendiceal) who are in good physical condition and have not had other cancer treatments in the past 2 years. They must be able to understand the study and agree to its terms. Pregnant women and those with serious heart conditions or infections are excluded.

Inclusion Criteria

I have taken a pregnancy test in the last 3 days and it was negative.

My pancreatic cancer can be surgically removed and hasn't spread far.

You are expected to live for at least 3 more months.

Exclusion Criteria

Is pregnant or breastfeeding

Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator

I haven't had a severe infection in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Folfirinox with or without Panitumumab and CEND-1 for 3 cycles, followed by surgery

Approximately 9 weeks

Multiple visits for infusions and biopsies

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term follow-up

Participants are monitored for overall survival and disease-free survival

48 months

What Are the Treatments Tested in This Trial?

Interventions

• CEND-1
• Folfirinox
• Panitumumab

Trial Overview

The safety of a new drug combination is being tested: CEND-1 with FOLFIRINOX chemotherapy, with some patients also receiving Panitumumab. The goal is to see how well these drugs work together against specific cancers before surgery.

How Is the Trial Designed?

Group I: Cohort 3 Oligomets Colon Cancer Experimental Treatment 3 Interventions

Biopsy for tissue immune profile if archived tissue not available. Folfirinox plus Panitumumab (if RAS/BRAF) infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Folfirinox plus Panitumumab (if RAS/BRAF positive) and CEND-1 infusion for 3 cycles. Seventy-two hours after last infusion participant will have surgery.

Group II: Cohort 2 Peritoneal Mets Experimental Treatment 3 Interventions

Biopsy for tissue immune profile if archived tissue not available. Folfirinox plus Panitumumab (if RAS/BRAF) infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Folfirinox plus Panitumumab (if RAS/BRAF positive) and CEND-1 infusion for 3 cycles. Seventy-two hours after last infusion participant will have surgery.

Group III: Cohort 1 Pancreatic Cancer Experimental Treatment 2 Interventions

Biopsy for tissue immune profile if archived tissue not available. Folfirinox infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Folfirinox plus CEND-1 infusion for 3 cycles. Seventy-two hours after last infusion participant will have surgery.

Who Is Running the Clinical Trial?

Anup Kasi

Lead Sponsor

Trials

1

Recruited

50+

Cend Therapeutics Inc.

Collaborator

Trials

2

Recruited

100+

Published Research Related to This Trial

In a study of 289 patients with advanced pancreatic ductal adenocarcinoma, the FOLFOXIRI chemotherapy regimen showed similar overall survival (11.1 months) compared to the standard FOLFIRINOX regimen (11.6 months), indicating no significant therapeutic advantage for FOLFOXIRI.

FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events (28.7% vs. 19.5% for FOLFIRINOX), suggesting that while it is feasible, it may lead to more severe side effects without improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. Vienot, A., Chevalier, H., Bolognini, C., et al.[2020]

In a real-world study of 362 patients with metastatic colorectal cancer treated with ramucirumab + FOLFIRI, 84.3% experienced adverse events, with common issues including decreased neutrophil count, hypertension, and diarrhea, indicating that while the treatment is effective, it does carry a significant risk of side effects.

The 12-month survival rate for patients on the ramucirumab + FOLFIRI regimen was 59%, with most mortality attributed to disease progression rather than treatment-related complications, suggesting that the regimen is manageable and aligns with previous clinical trial safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing safety study of ramucirumab with FOLFIRI in patients with metastatic colorectal cancer. Masuishi, T., Nagaoka, S., Jin, L., et al.[2022]

In a multicenter phase II study involving 31 chemotherapy-naïve Japanese patients with advanced pancreatic cancer, the modified FOLFIRINOX (mFX) regimen showed a response rate of 38.7% and a median overall survival of 14.9 months, indicating its efficacy as a first-line treatment.

While mFX resulted in fewer Grade 3 or 4 non-hematological adverse events compared to the standard FOLFIRINOX regimen, it still had a high incidence of hematological adverse events, particularly neutropenia (83.9%), suggesting the need for further optimization to enhance safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer. Yoshida, K., Iwashita, T., Uemura, S., et al.[2022]

FOLFIRINOX (FFX) has been shown to significantly improve median overall survival, progression-free survival, and objective response rates in patients with metastatic pancreatic cancer compared to gemcitabine, as established in the PRODIGE 4/ACCORD 11 study.

Despite initial concerns about its toxicity, FFX has been widely adopted in clinical practice, leading to new research opportunities and discussions about managing its side effects and optimizing treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic cancer and FOLFIRINOX: a new era and new questions. Marsh, Rde W., Talamonti, MS., Katz, MH., et al.[2023]

Neoadjuvant FOLFIRINOX treatment in patients with borderline resectable pancreatic cancer (BRPC) resulted in a median overall survival of 22.2 months and a high resection rate of 67.8%, indicating its potential effectiveness in this patient group.

The treatment was associated with manageable adverse events, with the most common being neutropenia, diarrhea, and fatigue, but no deaths were reported due to FOLFIRINOX, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. Janssen, QP., Buettner, S., Suker, M., et al.[2021]

In a study of 243 patients with advanced pancreatic adenocarcinoma treated with FOLFIRINOX, the relative dose intensity (RDI) of the treatment agents did not significantly correlate with disease control or objective response, suggesting that dose reductions may not compromise treatment effectiveness.

The median cumulative multi-drug RDI was 80%, and including RDI in predictive models did not enhance the ability to forecast disease control, indicating that oncologists can safely adjust doses without fearing a loss of therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. Vary, A., Lebellec, L., Di Fiore, F., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05121038

Study Details | NCT05121038 | CEND-1 in Combination ...

Patients with histologically confirmed pancreatic ductal adenocarcinomas, colorectal and appendiceal adenocarcinomas; For cohort 1: Resectable Pancreatic Cancer ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e16274

Updated single institution outcome data from the first-in- ...

Conclusions: Ongoing follow-up data from the CEND-1 study at our institution shows ongoing continuing benefit for patients who remain on trial ...

3.

cancernetwork.com

cancernetwork.com/view/certepetide-folfirinox-displays-encouraging-preliminary-feasibility-in-pdac

Certepetide/FOLFIRINOX Displays Encouraging ...

The addition of certepetide to a FOLFIRINOX-based regimen was safe in patients with resectable or borderline resectable pancreatic ductal ...

4.

ir.lisata.com

ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-encouraging-preliminary-results

Press Release Details

The abstract highlights that the combination of certepetide with FOLFIRINOX was safe and feasible in patients with resectable and borderline ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4988311/

Towards personalized therapy in pancreatic cancer - PMC

In a phase II trial 46 patients receiving FOLFIRINOX for advanced pancreatic cancer showed a response rate of 26%, including 4% complete response. Median time ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11430066/

A Nationwide Population-Based Study in Korea - PMC

This study investigated the nationwide real-world outcomes of chemotherapy in 8651 patients with metastatic pancreatic cancer.