OT-101 + mFOLFIRINOX for Pancreatic Cancer

(STOP-PC Trial)

Recruiting at 1 trial location

Overseen By Cynthia Lee, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Oncotelic Inc.

Must not be taking: Anticoagulants, NSAIDs, Corticosteroids, others

Disqualifiers: Other cancers, Infections, Cardiac events, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2.5 years

455 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of the new drug OT-101 when combined with a standard treatment called mFOLFIRINOX (a chemotherapy regimen), compared to mFOLFIRINOX alone, for individuals with advanced pancreatic cancer that cannot be surgically removed or has metastasized. Participants will receive either the combination of OT-101 and mFOLFIRINOX or just mFOLFIRINOX. The study seeks individuals diagnosed with advanced pancreatic cancer that impacts daily life and cannot be treated with surgery. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering hope for new treatment options.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including investigational agents, anti-coagulants (except heparin for catheters), non-steroidal anti-inflammatory drugs, and specific drugs that affect platelet function. If you are on these medications, you may need to stop them to participate in the study.

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

Research shows that OT-101, combined with mFOLFIRINOX, is under evaluation for safety and effectiveness in treating pancreatic cancer. Earlier patients using OT-101 lived longer on average, particularly those with low levels of the protein TGF-β2, suggesting the treatment might be promising.

Regarding safety, mFOLFIRINOX alone is known to be safer than traditional FOLFIRINOX, typically causing fewer or less severe side effects. Researchers continue to study how well patients tolerate the combination with OT-101 and what side effects might occur.

Although OT-101 is not yet widely approved, ongoing studies like this one are crucial for understanding its safety and effectiveness with mFOLFIRINOX. Participants in these trials provide valuable information on the safety and tolerability of these treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about the combination of OT-101 with mFOLFIRINOX for pancreatic cancer because it offers a new approach to treatment. Unlike standard treatments that primarily rely on chemotherapy alone, OT-101 targets a specific protein involved in cancer growth, potentially enhancing the efficacy of chemotherapy. This dual-action strategy could lead to better outcomes by both directly attacking the cancer cells and disrupting their growth signals. By combining OT-101 with mFOLFIRINOX, there's hope for improved effectiveness and a new avenue for tackling this challenging disease.

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

In this trial, participants will receive either the combination of OT-101 with mFOLFIRINOX or mFOLFIRINOX alone. Research shows that combining OT-101 with mFOLFIRINOX may hold promise for treating advanced pancreatic cancer. One study found that OT-101 helped patients live longer, with a median survival of over 34 months, particularly in those with low levels of the protein TGF-β2. Modified FOLFIRINOX alone has already been linked to better survival rates compared to surgery alone for pancreatic cancer patients. This suggests that using OT-101 with mFOLFIRINOX could be more effective than using mFOLFIRINOX by itself. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced, inoperable or metastatic pancreatic cancer. Participants must have measurable disease, not be pregnant or breastfeeding, and agree to use contraception. They should have completed prior treatments with recovery from most side effects and have good performance status indicating they can carry out daily activities.

Inclusion Criteria

Provide signed written informed consent

Measurable disease per RECIST v.1.1

I will use effective birth control for 6 months after my last oxaliplatin dose.

Exclusion Criteria

Any serious medical condition, laboratory abnormality, psychiatric illness, or comorbidity that, in the judgment of the Investigator, would make the patient inappropriate for the study

Patients with abnormal electrocardiogram (ECG) at baseline (QT or QTc interval >470 ms)

I am currently taking prescribed medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OT-101 in combination with mFOLFIRINOX or mFOLFIRINOX alone in 14-day cycles

2.5 years

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• mFOLFIRINOX
• OT-101

Trial Overview The study tests OT-101 combined with mFOLFIRINOX (a mix of folinic acid, 5-FU, irinotecan, oxaliplatin) against mFOLFIRINOX alone in treating pancreatic cancer. The aim is to see which treatment is more effective and safe.

How Is the Trial Designed?

Group I: OT-101 + mFOLFIRINOX Active Control 2 Interventions

OT-101 IV dosed on Days 4-7 plus mFOLFIRINOX (dl-LV 400 mg/m2, irinotecan 180 mg/m2 and oxaliplatin 85 mg/m2 followed by a 46-hour infusion of 5-FU 2400 mg/m2) initiated on Day 1 of a 14-day cycle

Group II: mFOLFIRINOX Only Placebo Group 1 Intervention

mFOLFIRINOX (dl-LV 400 mg/m2, irinotecan 180 mg/m2 and oxaliplatin 85 mg/m2 followed by a 46-hour infusion of 5-FU 2400 mg/m2) initiated on Day 1 of a 14-day cycle

mFOLFIRINOX is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as mFOLFIRINOX for:

• Pancreatic ductal adenocarcinoma (PDAC)

Approved in United States as mFOLFIRINOX for:

• Advanced pancreatic cancer

Approved in Canada as mFOLFIRINOX for:

• Resectable pancreatic ductal adenocarcinoma

Who Is Running the Clinical Trial?

Oncotelic Inc.

Lead Sponsor

Trials

3

Recruited

540+

Published Research Related to This Trial

In a study of 318 patients with metastatic pancreatic cancer, the modified FOLFIRINOX (mFFX) regimen showed similar overall survival and progression-free survival compared to the original FOLFIRINOX (oFFX) regimen, indicating that mFFX is just as effective.

mFFX was associated with significantly fewer adverse events, such as thrombopenia and liver dysfunction, making it a safer option for patients compared to oFFX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Retrospective Analysis of Original versus Modified FOLFIRINOX in Metastatic Pancreatic Cancer: Results of the NAPOLEON Study. Nakazawa, J., Tsuruta, N., Shimokawa, M., et al.[2023]

Modified FOLFIRINOX shows similar effectiveness in treating metastatic pancreatic adenocarcinoma (MPA) compared to standard FOLFIRINOX, with no significant differences in overall survival or progression-free survival among patients.

While modified FOLFIRINOX had a lower dose reduction rate, it was associated with a slightly higher incidence of severe toxicity, indicating that patient selection may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma. de Jesus, VHF., Camandaroba, MPG., Donadio, MDS., et al.[2023]

The modified FOLFIRINOX regimen is effective and well-tolerated for patients with advanced nonmetastatic pancreatic cancer, showing a high rate of surgical resection (72% attempted, 51.1% accomplished) with manageable toxicity, primarily diarrhea in 14% of patients.

Patients who underwent surgical resection after treatment with mFOLFIRINOX experienced a median progression-free survival of 18 months, significantly longer than the 8 months for those who did not have surgery, indicating a potential survival benefit from this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Blazer, M., Wu, C., Goldberg, RM., et al.[2022]

Modified-dose FOLFIRINOX (mFOLFIRINOX) demonstrated comparable efficacy to standard-dose FOLFIRINOX (sFOLFIRINOX) in treating pancreatic cancer, with similar objective response rates and overall survival outcomes among 130 patients studied.

mFOLFIRINOX was associated with significantly lower rates of severe adverse events, such as neutropenia, anorexia, and diarrhea, suggesting it is a safer option for patients who may be concerned about toxicity while maintaining effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. Kang, H., Jo, JH., Lee, HS., et al.[2022]

In a study of 198 patients with advanced pancreatic cancer, the SOXIRI chemotherapy regimen showed similar overall survival (12.1 months) and progression-free survival (6.5 months) compared to the standard mFOLFIRINOX regimen (11.2 months and 6.8 months, respectively), indicating comparable efficacy.

While both regimens had similar safety profiles, SOXIRI was associated with a higher incidence of anemia (41.4% vs. 24%), suggesting that while effective, it may have specific side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. Li, X., Huang, J., Wang, F., et al.[2023]

The modified FOLFIRINOX (mFOLFIRINOX) regimen showed a tolerable safety profile with lower hematological toxicity compared to the full-dose FOLFIRINOX, while still maintaining comparable efficacy in treating advanced pancreatic ductal adenocarcinoma (PDAC).

In a study of 18 patients, 80% achieved at least stable disease, with a median overall survival of 9.3 months and progression-free survival of 7.2 months, indicating that mFOLFIRINOX can be an effective treatment option for fit patients with advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. Ghorani, E., Wong, HH., Hewitt, C., et al.[2023]

In a phase III trial involving 80 patients with metastatic pancreatic adenocarcinoma, modified FOLFIRINOX (mFOLFIRINOX) significantly improved overall survival compared to S-1, with median survival rates of 9.2 months versus 4.9 months, respectively.

While mFOLFIRINOX showed higher efficacy with better response and disease control rates, it also resulted in more severe adverse events, with 56% of patients experiencing grade 3-4 side effects compared to 17% in the S-1 group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX versus S-1 as second-line chemotherapy in gemcitabine-failed metastatic pancreatic cancer patients: A randomised controlled trial (MPACA-3). Go, SI., Lee, SC., Bae, WK., et al.[2022]

The modified FOLFIRINOX (mFOLFIRINOX) regimen demonstrated a high treatment efficacy in patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC), achieving a response rate of 55.2% among 29 evaluable patients.

The treatment was well-tolerated, with only 9 patients experiencing grade 3 or 4 adverse effects, and no patients discontinued treatment due to side effects, indicating a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. Bai, X., Su, R., Ma, T., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06079346

NCT06079346 | A Study of OT-101 With mFOLFIRINOX in ... The goal of this clinical study is to compare the efficacy and safety of OT-101 in combination with mFOLFIRINOX (folinic acid, 5-FU, irinotecan, oxaliplatin) ...

2. stop-pc.com stop-pc.com/

STOP-PC clinical trial — Pancreatic Cancer Clinical Trial ... OT-101 extended median survival to over 34 months in patients with low TGF-β2 expression. Importantly, the modified FOLFIRINOX regimen (mFOLFIRINOX) used in ...

3. letswinpc.org letswinpc.org/research/immunotherapy-clinical-trial-recruiting/

Immunotherapy Clinical Trial Recruiting This phase IIb/phase III study will compare OT-101 plus mFOLFIRINOX versus mFOLFIRINOX alone as first-line therapy, in newly diagnosed patients ...

4. cancernetwork.com cancernetwork.com/view/perioperative-modified-folfirinox-shows-encouraging-outcomes-in-pancreatic-cancer

Perioperative Modified FOLFIRINOX Shows Encouraging ... Modified FOLFIRINOX (mFOLFIRINOX) was associated with better outcomes with longer survival rates vs surgery alone for patients with pancreatic ductal ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9229892/

A Single-Center Retrospective Study to Compare the ... This single-center retrospective study aimed to compare the efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) with S-1 as ACT for resected PC.

6. letswinpc.org letswinpc.org/research/chemo-rna-immunotherapy-combination/

Testing a New Chemo and RNA Therapy Combination This trial will compare the efficacy and safety of OT-101 in combination with mFOLFIRINOX to treatment with mFOLFIRINOX alone, in patients with advanced and ...

7. app.trialscreen.org app.trialscreen.org/trials/phase-2-3-ot-101-folfirinox-patients-advanced-unresectable-or-metastatic-trial-nct06079346

A Study of OT-101 With mFOLFIRINOX in Patients ... This Interventional study is looking for people with Pancreatic Ductal Adenocarcinoma in Detroit United States, Houston United States to take part.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6247105/

Comparison of efficacy and safety between standard-dose ... mFOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose ...