Intraperitoneal Chemotherapy for Colorectal Cancer

(ICARuS Trial)

Not currently recruiting at 9 trial locations

Overseen By Andrea Cercek, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, Coronary artery disease, Hypertension, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post-surgery

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare two types of chemotherapy treatments, EPIC and HIPEC, administered directly into the abdomen after surgery for appendiceal or colorectal cancer. Researchers seek to understand the positive and negative effects of these treatments on patients following cancer surgery. Individuals diagnosed with cancer in the appendix, colon, or rectum who plan to undergo surgery to remove abdominal cancer may be suitable candidates. Participants will be divided into groups based on recent chemotherapy history and cancer location and will receive one of the two treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking an oral medication that cannot be safely stopped for up to ten days, it may be a concern for participation.

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

Research has shown that EPIC and HIPEC treatments have different safety levels. For HIPEC, studies indicate it is generally well-tolerated but can lead to moderate to high rates of complications, such as infections or bowel problems. Some research suggests that HIPEC can improve outcomes for certain patients.

For EPIC, early findings suggest it might have similar risks to HIPEC, though detailed information is limited. It typically involves delivering chemotherapy directly into the abdomen, which can cause side effects, but the safety details are not as well-documented.

Both treatments remain under study, and this trial aims to compare their effects. Participants should discuss potential risks and benefits with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about intraperitoneal chemotherapy for colorectal cancer because it offers a unique approach compared to standard treatments like systemic chemotherapy. This method involves delivering chemotherapy directly into the abdominal cavity, targeting cancer cells more precisely and potentially reducing systemic side effects. The trial explores two techniques: HIPEC (Hyperthermic Intraperitoneal Chemotherapy) and EPIC (Early Postoperative Intraperitoneal Chemotherapy). HIPEC involves heating the chemotherapy, which may enhance its effectiveness, while EPIC is administered immediately after surgery, allowing for early intervention. These innovative strategies aim to improve outcomes by focusing on localized treatment, offering hope for better control of cancer within the abdomen.

What evidence suggests that this trial's treatments could be effective for appendiceal and colorectal cancer?

This trial will compare two treatments, HIPEC and EPIC, for colorectal and appendiceal cancers. Studies have shown that HIPEC, which delivers heated chemotherapy directly into the abdominal area, has improved survival rates for patients with cancer that has spread to the abdominal lining from colorectal cancer. Evidence suggests a significant reduction in cancer recurrence when using HIPEC after surgery compared to surgery alone. Meanwhile, EPIC, which involves administering chemotherapy directly into the abdomen soon after surgery, can also help reduce cancer spread, although its effectiveness compared to HIPEC remains under investigation. Both treatments in this trial aim to directly target and kill any remaining cancer cells after surgery, potentially leading to better outcomes for patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Garrett Nash, MD, MPH

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with appendiceal or colorectal cancer that has spread to the lining of the abdomen, who are fit enough for surgery and have no other serious medical conditions. They must not be pregnant, should agree to use contraception, and cannot have had prior intraperitoneal chemotherapy.

Inclusion Criteria

Women with childbearing potential who are negative for pregnancy test (urine or blood) and who agree to use effective contraceptive method. Reliable contraception should be used from trial screening and must be continued throughout the study. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant

I agree to use reliable contraception throughout the study.

I am scheduled for surgery to remove all cancer from my abdomen.

Exclusion Criteria

I am allergic to floxuridine, leucovorin, or mitomycin.

I have heart failure that affects my daily activities.

I do not have a history of stroke or brain blood vessel issues that would make this study unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cytoreductive Surgery

Patients undergo optimal cytoreductive surgery to reduce tumor nodules to no greater than 2.5mm

1 week

Treatment

Participants receive either Early Post-operative Intraperitoneal Chemotherapy (EPIC) or Hyperthermic Intraperitoneal Chemotherapy (HIPEC) after surgery

Immediate post-surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of chemotherapy and surgical toxicities

60 days

Long-term Follow-up

Documentation of tumor recurrence based on surveillance CT/PET CT scans

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cytoreductive Surgery
• FUDR
• Leucovorin
• Mitomycin-C

Trial Overview The study compares two types of chemotherapy given after surgery to remove all visible cancer from the abdomen: EPIC (chemo directly into the abdomen post-surgery) and HIPEC (heated chemo during surgery). It aims to determine their effectiveness against abdominal cancers.

How Is the Trial Designed?

Group I: Colorectal, no chemotherapy within 6 months prior to surgery Experimental Treatment 3 Interventions

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the PI or Co-PI. 1. Exposure to chemotherapy in the prior 6 months vs. no such exposure 2. Appendix vs. Colon or Rectum • Then, patients will be randomly assigned in the operating room, by envelope, to either HIPEC (Group A) or EPIC (Group B) after the operating surgeon determines that the patient is optimally cytoreduced to nodules no greater than 2.5mm.

Group II: Colorectal, chemotherapy within 6 months prior to surgery Experimental Treatment 3 Interventions

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the PI or Co-PI. 1. Exposure to chemotherapy in the prior 6 months vs. no such exposure 2. Appendix vs. Colon or Rectum • Then, patients will be randomly assigned in the operating room, by envelope, to either HIPEC (Group A) or EPIC (Group B) after the operating surgeon determines that the patient is optimally cytoreduced to nodules no greater than 2.5mm.

Group III: Appendiceal, no chemotherapy within 6 months prior to surgery Experimental Treatment 3 Interventions

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the PI or Co-PI. 1. Exposure to chemotherapy in the prior 6 months vs. no such exposure 2. Appendix vs. Colon or Rectum Then, patients will be randomly assigned in the operating room, by envelope, to either HIPEC (Group A) or EPIC (Group B) after the operating surgeon determines that the patient is optimally cytoreduced to nodules no greater than 2.5mm.

Group IV: Appendiceal, chemotherapy within 6 months prior to surgery Experimental Treatment 3 Interventions

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the PI or Co-PI. 1. Exposure to chemotherapy in the prior 6 months vs. no such exposure 2. Appendix vs. Colon or Rectum • Then, patients will be randomly assigned in the operating room, by envelope, to either HIPEC (Group A) or EPIC (Group B) after the operating surgeon determines that the patient is optimally cytoreduced to nodules no greater than 2.5mm.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a study of 147 patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, the overall postoperative complication rate was 37%, with a mortality rate of 2%.

The Clavien-Dindo classification system identified a significantly higher rate of major morbidity (25%) compared to the CTCAE classification (8%), suggesting that the Clavien-Dindo system may provide a clearer and more user-friendly assessment of surgical complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Where Oncologic and Surgical Complication Scoring Systems Collide: Time for a New Consensus for CRS/HIPEC. Lehmann, K., Eshmuminov, D., Slankamenac, K., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12317892/

Great Debate: Hyperthermic Intraperitoneal Chemotherapy for ... The journey to recognizing CRS-HIPEC's potential began with a 1992 observational study that reported a striking contrast: 20% survival rate at 2 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.160

Colorectal cohort analysis from the Intraperitoneal ... The trial was originally powered to evaluate 212 patients for a 20% gain in a primary endpoint of 3-year progression free survival (PFS: HR = ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1421019/

Intraperitoneal Chemotherapy: Biologic Implications for ... For cancers of the large bowel, several large multiinstitutional trials have demonstrated a significant reduction in mortality using surgery plus adjuvant ...

4. ejcancer.com ejcancer.com/article/S0959-8049(24)01761-1/fulltext

Safety and efficacy of adjuvant FOLFOX/FOLFIRI with ... Hepatic artery infusion (HAI) chemotherapy, particularly with floxuridine (FUDR), has previously shown effectiveness in improving recurrence-free survival ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04898504

Study Details | NCT04898504 | HAI-Floxuridine, or Liver-Tx ... The treatment option for the majority of the patients is palliative chemotherapy with median overall survival from start of chemotherapy of about 2 years and 10 ...

6. clinicaltrials.eu clinicaltrials.eu/inn/floxuridine/

Floxuridine – Application in Therapy and Current Clinical ... Floxuridine (FUDR) is a chemotherapy drug that is being studied for treating colorectal cancer that has spread to the liver. In these trials, it is typically ...

7. withpower.com withpower.com/trial/phase-3-appendiceal-neoplasms-2-2013-d7b95

Intraperitoneal Chemotherapy for Colorectal Cancer (ICARuS Trial) Intraperitoneal chemotherapy combined with surgery for colorectal cancer can lead to moderate to high rates of complications and risks, but it is a treatment ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2003.04.187

Randomized Trial of Cytoreduction and Hyperthermic ... Purpose: To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0748798323005693

A narrative review of what can HIPEC do Perioperative intraperitoneal chemotherapy can be expected to eradicate free cancer cells or minute cancer nodules free floating in the fluid within peritoneal ...