Intraperitoneal Chemotherapy for Colorectal Cancer

(ICARuS Trial)

Recruiting at 8 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

292 Participants Needed

Trial Summary

What is the purpose of this trial?

This is the first randomized trial comparing Early post-operative intraperitoneal chemotherapy (EPIC) and hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancer. The purpose of this study is to find out what effects, good and/or bad, EPIC and HIPEC after cytoreductive surgery have on the patient and the appendiceal, rectal or colon cancer.

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.

What data supports the effectiveness of the treatment involving Cytoreductive Surgery, FUDR, Leucovorin, Mitomycin-C, and other components for colorectal cancer?

Research shows that combining cytoreductive surgery with intraperitoneal chemotherapy can improve survival for patients with colorectal cancer that has spread to the peritoneum (the lining of the abdominal cavity), although it may come with higher risks during and after surgery. ^{1 2 3 4 5}

Is intraperitoneal chemotherapy for colorectal cancer safe?

Intraperitoneal chemotherapy combined with surgery for colorectal cancer can lead to moderate to high rates of complications and risks, but it is a treatment option for certain patients. Safety data shows that while it can be effective, it comes with significant risks that need to be carefully considered. ^{5 6 7 8 9}

How is the treatment of cytoreductive surgery with intraperitoneal chemotherapy unique for colorectal cancer?

This treatment is unique because it combines surgery to remove visible tumors with chemotherapy delivered directly into the abdominal cavity, targeting cancer cells more directly than traditional methods. It is particularly used for patients with cancer spread to the lining of the abdomen, offering a more localized approach compared to standard chemotherapy. ^{4 5 10 11 12}

Research Team

Garrett Nash, MD, MPH

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour associated with an improved survival. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Outcomes following surgery for colorectal cancer with synchronous peritoneal metastases. [2011]

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

Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma. [2022]

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

Selection of patients with colorectal peritoneal carcinomatosis for cytoreductive surgery and perioperative intraperitoneal chemotherapy. [2022]

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

Where Oncologic and Surgical Complication Scoring Systems Collide: Time for a New Consensus for CRS/HIPEC. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection: a randomized, multicenter, prospective, phase III IOCCRC trial (IOCCRC). [2018]

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

Perioperative Systemic Therapy Versus Cytoreductive Surgery and HIPEC Alone for Resectable Colorectal Peritoneal Metastases: Patient-Reported Outcomes of a Randomized Phase II Trial. [2023]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy With Mitomycin C Used for Colorectal Peritoneal Carcinomatosis. [2020]

10. China pubmed.ncbi.nlm.nih.gov

A pharmacological review on intraperitoneal chemotherapy for peritoneal malignancy. [2022]

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

Treatment failure following complete cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal dissemination from colorectal or appendiceal mucinous neoplasms. [2008]

12. England pubmed.ncbi.nlm.nih.gov

Cytoreductive surgery with intraperitoneal chemotherapy in the management of peritoneal surface malignancy: a pharmacist's perspective. [2022]