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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with resectable pancreatic cancer. Researchers are testing a combination of two treatments: ivosidenib (Tibsovo), which targets a specific genetic mutation, and mFOLFIRINOX, a chemotherapy regimen. The goal is to determine if this combination is effective before surgery. This trial may suit someone with confirmed pancreatic cancer that can be surgically removed and who hasn't received previous treatments for their cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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

Research shows that ivosidenib, when combined with mFOLFIRINOX, is under evaluation for safety and effectiveness in treating pancreatic cancer. Previous studies on mFOLFIRINOX have found it generally causes fewer side effects than the original FOLFIRINOX treatment, suggesting it might be easier for patients to handle.

Researchers are carefully studying ivosidenib's safety when combined with mFOLFIRINOX, as this combination is relatively new. The current research phase aims to assess patient tolerance and identify any possible side effects. Although data collection from this study is ongoing, past use of these treatments offers hope that they might be safe when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment options for pancreatic cancer, which often include combinations like FOLFIRINOX, the investigational treatment combining Ivosidenib with mFOLFIRINOX is unique because of its targeted approach. Ivosidenib specifically targets the IDH1 mutation, a genetic alteration found in some cancers, which allows it to potentially disrupt cancer growth more precisely than traditional methods. Researchers are excited about this combination because it could offer a more personalized therapy that directly impacts the cancer cells' abnormal pathways, possibly leading to more effective outcomes and fewer side effects.

What evidence suggests that Ivosidenib + mFOLFIRINOX might be an effective treatment for pancreatic cancer?

Research has shown that combining ivosidenib with a modified version of FOLFIRINOX chemotherapy, which participants in this trial will receive, may help treat pancreatic cancer. This modified chemotherapy has proven effective in about 31% of cases where the cancer is advanced or has spread. Studies suggest that ivosidenib, which targets a specific mutation called IDH1, can enhance the effectiveness of chemotherapy. This combination might help chemotherapy kill cancer cells more effectively. Early research in pancreatic cancer models demonstrated better results when ivosidenib was used with chemotherapy. ^{1 6 7 8 9}

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

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 (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 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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-1-pancreatic-adenocarcinoma-ductal-adenocarcinoma-5-2022-07a65

Ivosidenib + mFOLFIRINOX for Pancreatic Cancer Modified FOLFIRINOX (mFOLFIRINOX) showed moderate efficacy in treating locally advanced or metastatic pancreatic cancer, with a response rate of 30.8% and a ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-05224

Ivosidenib and Combination Chemotherapy ... This phase I trial tests the safety, side effects, and best dose of ivosidenib with modified FOLFIRINOX in treating patients with pancreatic cancer that can be ...

3. aacrjournals.org aacrjournals.org/cancerres/article/84/18/3072/747786/IDH1-Inhibition-Potentiates-Chemotherapy-Efficacy

IDH1 Inhibition Potentiates Chemotherapy Efficacy in ... Pancreatic ductal adenocarcinoma (PDAC) is associated with a 5-year overall survival rate of just 13%, and development of chemotherapy ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10516216/

Clinical Utility of Ivosidenib in the Treatment of IDH1-Mutant ... In pancreatic cancer models, similar effects were observed, with enhancement of chemotherapy efficacy and apoptosis, when combined with ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/17588359231171574

Updated survival outcomes with ivosidenib in patients ... Here we report the updated survival results of 11 patients with locally advanced or metastatic IDH1-mutated CCA who received ivosidenib in clinical practice.

6. withpower.com withpower.com/trial/phase-1-pancreatic-adenocarcinoma-ductal-adenocarcinoma-5-2022-07a65?lat=34.60184&lng=-117.81218

Ivosidenib + mFOLFIRINOX for Pancreatic Cancer This trial is testing whether adding a new drug, ivosidenib, to an existing chemotherapy treatment can improve outcomes for patients with pancreatic cancer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7054309/

Efficacy and safety of FOLFIRINOX as salvage treatment in ... The objective of this study was to evaluate safety and anti-tumour activity of fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) as salvage ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05209074

Study Details | NCT05209074 | Ivosidenib + mFOLFIRINOX ... This study is a single-arm, phase I trial, up to 16 participants with resectable PDA. The study will examine the efficacy of the mutant IDH1 inhibitor ...

9. mdpi.com mdpi.com/2072-6694/14/8/1950

Modified FOLFIRINOX as a Second-Line Treatment for ... Compared to the previous original regimen of FOLFIRINOX, the survival outcomes and response rate of mFOLFIRINOX were comparable and presented fewer AEs in ...