What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, such as FOLFIRINOX and gemcitabine, are associated with a range of side effects. FOLFIRINOX, a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin, often causes severe side effects including neutropenia, fatigue, diarrhea, nausea, and peripheral neuropathy. Gemcitabine, another standard chemotherapy agent, can lead to side effects such as myelosuppression, flu-like symptoms, fatigue, and gastrointestinal disturbances. Targeted therapies, like the mutant IDH1 inhibitor Ivosidenib, may cause side effects such as fatigue, nausea, diarrhea, and elevated liver enzymes. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for pancreatic cancer, particularly for patients with specific genetic mutations. For instance, olaparib, a PARP inhibitor, is approved for patients with germline BRCA-mutated metastatic pancreatic cancer. Additionally, pembrolizumab, an immune checkpoint inhibitor, is approved for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. While ivosidenib, a mutant IDH1 inhibitor, is being studied for its efficacy in pancreatic cancer, it is not yet FDA-approved for this indication. These treatments represent a shift towards personalized medicine in pancreatic cancer therapy.

What other types of research exist?

Promising novel alternatives to Ivosidenib for pancreatic cancer patients include: 1) PARP inhibitors like Olaparib for patients with BRCA mutations, 2) Combination therapies such as mFOLFIRINOX, and 3) Immune checkpoint inhibitors like Nivolumab and Pembrolizumab, especially in combination with other agents. These alternatives have shown efficacy in clinical trials and offer different mechanisms of action that may benefit patients with pancreatic cancer.

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Mutant IDH1 Inhibitor

Ivosidenib + mFOLFIRINOX for Pancreatic Cancer

Phase 1

Recruiting

Led By David Bajor, MD

Research Sponsored by Case Comprehensive Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects must have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma or adenosquamous carcinoma

No evidence of clinically significant active infection and no serious or chronic infection requiring ongoing antibiotics

Must not have

Subjects with metastatic pancreatic cancer based on imaging

Subjects with uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure or coronary artery disease, unstable angina pectoris, cardiac arrhythmia requiring medications that interact with ivosidenib, symptomatic myocardial infarction or psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months from the start of treatment

Awards & highlights

No Placebo-Only Group

Approved for 5 Other Conditions

All Individual Drugs Already Approved

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Ivosidenib may cause side effects like fatigue, joint pain, skin problems or changes in blood counts which could lead to infections or bleeding issues. The mFOLFIRINOX regimen has its own risks including nausea, diarrhea, low blood cell counts and nerve damage.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is confirmed as pancreatic adenocarcinoma or adenosquamous carcinoma.

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I don't have any serious infections or need for ongoing antibiotics.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My pancreatic cancer has spread, as shown by scans.

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I do not have any severe ongoing illnesses that would interfere with the study.

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I have had treatment for pancreatic cancer before.

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I am not pregnant, breastfeeding, or if capable of becoming pregnant, I am using reliable contraception.

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I am a man who can father children and will not use birth control during the study.

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I am not HIV-positive or not on antiretroviral therapy.

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My pancreatic cancer is advanced or has come back.

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I am under 18 years old.

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My cancer is a type of pancreatic cancer.

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My pancreatic cancer cannot be removed by surgery or is in the left side (body/tail) and can be.

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I do not have any ongoing, uncontrolled bleeding issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months from the start of treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months from the start of treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months from the start of treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum-tolerated dose (MTD) or Recommended Phase 2 dose (RP2D)

Secondary study objectives

Biochemical response rates

Major pathologic response rates

RECIST version 1.1 response rates.

Side effects data

From 2023 Phase 1 trial • 9 Patients • NCT03885284

67%

Abdominal pain

67%

Nausea

33%

Weight loss

33%

Diarrhea

33%

Fatigue

33%

Postnasal drip

33%

Alanine aminotransferase increased

33%

Alkaline phosphatase increased

33%

Aspartate aminotransferase increased

33%

Peripheral sensory neuropathy

33%

Platelet count decreased

100%

80%

60%

40%

20%

Study treatment Arm

Dose Level 1

Dose Level 2

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Ivosidenib+mFOLFIRINOXExperimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ivosidenib

FDA approved

mFOLFIRINOX

2013

Completed Phase 2

~90

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for pancreatic cancer include platinum-based chemotherapy, PARP inhibitors, and investigational therapies like the mutant IDH1 inhibitor ivosidenib. Platinum-based chemotherapy works by causing DNA crosslinking, which leads to cell death, particularly in cells with homologous recombination repair (HRR) deficiencies. PARP inhibitors exploit the defective DNA repair mechanisms in cancer cells with BRCA mutations, leading to cell death through synthetic lethality. Ivosidenib targets mutant IDH1, an enzyme that contributes to cancer cell metabolism and growth. These treatments are significant because they target specific vulnerabilities in pancreatic cancer cells, potentially improving outcomes for patients with advanced or genetically predisposed forms of the disease.