CEND-1 + FOLFIRINOX for Digestive Cancer

(CENDIFOX Trial)

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

50 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment CEND-1 + FOLFIRINOX for digestive cancer?

Research shows that FOLFIRINOX, a part of the treatment, has been effective in improving survival and quality of life in patients with pancreatic cancer compared to other treatments. It has shown better progression-free survival and overall survival in patients with borderline resectable pancreatic cancer compared to a gemcitabine-based regimen. ^{1 2 3 4 5}

Is the combination of CEND-1 and FOLFIRINOX safe for humans?

FOLFIRINOX, a part of the treatment combination, is known to cause significant side effects, including blood-related issues like febrile neutropenia (a condition with fever and low white blood cells) and other toxic effects, which often require dose adjustments or stopping the treatment. ^{2 6 7 8 9}

What makes the CEND-1 + FOLFIRINOX treatment unique for digestive cancer?

The CEND-1 + FOLFIRINOX treatment is unique because it combines CEND-1, a novel agent, with FOLFIRINOX, a chemotherapy regimen known for its effectiveness in pancreatic cancer. This combination aims to enhance the delivery and effectiveness of chemotherapy, potentially offering a new approach for treating digestive cancers. ^{1 2 3 5 8}

What is the purpose of this trial?

This is a phase IB/IIA trial to ensure the safety of Certepetide (LSTA1/CEND-1) in combination with with Folfirinox with or without Panitumumab for treatment of pancreatic, colon and appendiceal cancers

Research Team

Anup Kasi, MD

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Pancreatic cancer and FOLFIRINOX: a new era and new questions. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of FOLFIRINOX: a review of studies and parameters. [2019]

3. China pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. [2020]

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

Efficacy and safety of neoadjuvant FOLFIRINOX for borderline resectable pancreatic adenocarcinoma: improved efficacy compared with gemcitabine-based regimen. [2018]

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

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. [2022]

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

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer. [2022]

8. China pubmed.ncbi.nlm.nih.gov

Chemoradiation after FOLFIRINOX for borderline resectable or locally advanced pancreatic cancer. [2022]

9. China pubmed.ncbi.nlm.nih.gov

A post-marketing safety study of ramucirumab with FOLFIRI in patients with metastatic colorectal cancer. [2022]