Ivosidenib + mFOLFIRINOX for Pancreatic Cancer

Overseen By David Bajor, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Antiretrovirals

Disqualifiers: Unresectable cancer, Metastatic cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing whether adding a new drug, ivosidenib, to an existing chemotherapy treatment can improve outcomes for patients with pancreatic cancer that can be surgically removed. Ivosidenib works by blocking an enzyme that helps cancer cells grow. Researchers hope this combination will be more effective than chemotherapy alone. Ivosidenib has shown effectiveness and tolerability in treating a specific type of leukemia when combined with another drug.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications that interact with ivosidenib or are receiving other treatments for pancreatic cancer, you may need to stop those.

Is the combination of Ivosidenib and mFOLFIRINOX safe for humans?

Modified FOLFIRINOX (mFOLFIRINOX) has been studied for pancreatic cancer and is generally considered to have fewer side effects than the standard version, but it can still cause significant side effects. These studies focused on pancreatic cancer, and while they don't include Ivosidenib, they provide some insight into the safety of mFOLFIRINOX. ^{1 2 3 4 5}

How is the drug Ivosidenib + mFOLFIRINOX unique for treating pancreatic cancer?

The combination of Ivosidenib with mFOLFIRINOX is unique because it combines a targeted therapy (Ivosidenib, which targets specific cancer cell mutations) with a modified chemotherapy regimen (mFOLFIRINOX, which is a less intense version of a standard chemotherapy treatment) to potentially improve outcomes for pancreatic cancer patients. ^{1 2 5 6 7}

What data supports the effectiveness of the treatment Ivosidenib + mFOLFIRINOX for pancreatic cancer?

Research shows that modified FOLFIRINOX (mFOLFIRINOX) is effective and safe for treating advanced pancreatic cancer, especially when other treatments like gemcitabine have failed. This suggests that mFOLFIRINOX could be a promising option for pancreatic cancer patients. ^{1 2 5 7 8}

Who Is on the Research Team?

David Bajor, M.D.

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with resectable pancreatic cancer, specifically adenocarcinoma or adenosquamous carcinoma. They must be in good health overall, have a life expectancy of at least 3 months, and not have had previous treatments for pancreatic cancer. Women who can bear children and men must use contraception.

Inclusion Criteria

I am fully active or can carry out light work.

Fertile men must practice effective contraceptive methods

Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Subjects with a life expectancy less than 3 months

My pancreatic cancer has spread, as shown by scans.

I have a serious illness that could make treatment more risky for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ivosidenib in conjunction with mFOLFIRINOX in the neoadjuvant setting

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ivosidenib
• mFOLFIRINOX

Trial Overview The study tests the effectiveness of ivosidenib combined with mFOLFIRINOX chemotherapy before surgery in patients with certain types of pancreatic cancer. It's a phase I trial to see how well this combination works as an initial treatment.

How Is the Trial Designed?

Group I: Ivosidenib+mFOLFIRINOX Experimental Treatment 2 Interventions

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

Approved in United States as Tibsovo for:

• Acute myeloid leukemia (AML) with IDH1 mutation

Approved in European Union as Tibsovo for:

• Acute myeloid leukemia (AML) with IDH1 mutation

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

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 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]

Modified FOLFIRINOX (mFOLFIRINOX) showed moderate efficacy in treating locally advanced or metastatic pancreatic cancer, with a response rate of 30.8% and a disease control rate of 69.2% in 13 patients after previous treatments failed.

The treatment was associated with a median overall survival of 176 days and significant adverse effects, including neutropenia in 38.5% of patients, indicating that while mFOLFIRINOX can be beneficial, it also carries risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX for Locally Advanced and Metastatic Pancreatic Cancer Patients Resistant to Gemcitabine and S-1 in Japan: A Single Institutional Experience. Umemura, A., Nitta, H., Sasaki, A., et al.[2022]

In a study of 54 patients with advanced pancreatic cancer, S-IROX showed a higher disease control rate (73.7%) compared to modified FOLFIRINOX (mFFX) (62.2%), indicating it may be more effective as a second-line treatment after gemcitabine plus nab-paclitaxel.

Both S-IROX and mFFX had similar overall survival rates (14.2 months for S-IROX and 11.5 months for mFFX) and tolerability, with no significant differences in severe side effects, suggesting both regimens are viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. Saito, K., Nakai, Y., Takahara, N., 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]

In a multicenter phase II study involving 31 patients with locally advanced pancreatic cancer (LAPC) and 44 with metastatic pancreatic cancer (MPC), modified FOLFIRINOX showed comparable efficacy to full-dose FOLFIRINOX in MPC, with a response rate of 35.1% and a median overall survival of 10.2 months.

The study found that modified FOLFIRINOX significantly reduced adverse events such as neutropenia, vomiting, and fatigue, while demonstrating notable efficacy in LAPC with a median progression-free survival of 17.8 months and overall survival of 26.6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Stein, SM., James, ES., Deng, Y., et al.[2022]

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]

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]

Citations

1. China 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. [2022]

2. England 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). [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX for Locally Advanced and Metastatic Pancreatic Cancer Patients Resistant to Gemcitabine and S-1 in Japan: A Single Institutional Experience. [2022]

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

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. [2018]

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

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. [2022]

7. China 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. [2023]