Intraperitoneal Oxaliplatin and Fluorouracil for the Treatment of Patients With Peritoneal Metastases From Colorectal Cancer

NCT ID: NCT06269978

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-31

Study Completion Date

2026-01-31

Brief Summary

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This phase I trial tests the safety, side effects, and best dose of intraperitoneal oxaliplatin and fluorouracil in treating patients with colorectal cancer that has spread to the peritoneal cavity (peritoneal metastasis). Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill cancer cells. Fluorouracil stops cells from making DNA and it may kill cancer cells. Both oxaliplatin and fluorouracil are approved by the Food and Drug Administration to treat patients with colorectal cancer, however administration of these drugs directly into the area between the muscles and organs in the abdomen (intraperitoneal) for the treatment of peritoneal metastases is experimental. Giving oxaliplatin and fluorouracil directly into the peritoneal space may be a safe and effective way of treating patients with peritoneal metastases from colorectal cancer.

Detailed Description

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PRIMARY OBJECTIVES:

I. Determine safety, tolerability, and maximally tolerated dose (MTD) of intraperitoneal (IP) fluorouracil (5FU)+oxaliplatin.

II. Determine pharmacokinetics (PK) of IP 5FU+oxaliplatin both in blood and peritoneal fluid.

SECONDARY OBJECTIVES:

I. Determine tumor-cell intrinsic effects, modulation of the tumor immune microenvironment, and changes in the makeup of circulating immune cells in response to IP 5FU+oxaliplatin.

II. Identify preliminary response from IP 5FU+oxaliplatin: assess the rate of conversion from unresectable to resectable (determined by peritoneal carcinomatosis index \[PCI\] decreasing to \< 20) and response rates by imaging criteria.

OUTLINE: This is a dose-escalation study of 5FU and oxaliplatin followed by a dose-expansion study.

Patients undergo placement of indwelling IP port for chemotherapy infusion. Patients receive oxaliplatin and 5FU over 1-2 hours via IP infusion on days 1 and 15 of each cycle. Cycles repeat every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy, biopsy, computed tomography (CT)/magnetic resonance imaging (MRI), and collection of blood samples at screening and on study and undergo collection of IP fluid samples on study.

After completion of study treatment, patients are followed up for 30 days. Patients with confirmed disease progression or who start a new anti-cancer therapy are followed up every 12 weeks until death, withdrawal of consent, or end of study.

Conditions

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Metastatic Colorectal Carcinoma Metastatic Malignant Neoplasm in the Peritoneum Stage IV Colorectal Cancer AJCC v8

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (oxaliplatin, 5FU)

Patients undergo placement of indwelling IP port for chemotherapy infusion. Patients receive oxaliplatin and 5FU over 1-2 hours via IP infusion on days 1 and 15 of each cycle. Cycles repeat every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy, biopsy, CT/MRI, and collection of blood samples at screening and on study and undergo collection of IP fluid samples on study.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood and IP fluid samples

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Diagnostic Laparoscopy

Intervention Type PROCEDURE

Undergo diagnostic laparoscopy

Fluorouracil

Intervention Type DRUG

Given via IP infusion

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Oxaliplatin

Intervention Type DRUG

Given via IP infusion

Surgical Procedure

Intervention Type PROCEDURE

Undergo placement of indwelling IP port

Interventions

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Biopsy

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo collection of blood and IP fluid samples

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Diagnostic Laparoscopy

Undergo diagnostic laparoscopy

Intervention Type PROCEDURE

Fluorouracil

Given via IP infusion

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Oxaliplatin

Given via IP infusion

Intervention Type DRUG

Surgical Procedure

Undergo placement of indwelling IP port

Intervention Type PROCEDURE

Other Intervention Names

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BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Magnetic Resonance Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery

Eligibility Criteria

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Inclusion Criteria

* Age \>= 18 years
* Biopsy proven colorectal cancer with peritoneal metastasis. Patients with extraperitoneal metastases will not be eligible. Patients with involvement of intra-abdominal lymph nodes may be eligible at the discretion of the treating physician
* Primary colorectal cancer may either be left in place or have been resected prior to study enrollment
* Patients are allowed to have received prior colorectal cancer-directed systemic therapy.
* Not previously undergone cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at the time of enrollment
* Absolute neutrophil count (ANC) ≥ 1,500 /mcL
* Platelets ≥ 100,000 / mcL
* Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥ 60 mL/min for patient with creatinine levels \> 1.5 x institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\])

* Creatinine clearance should be calculated per institutional standard
* Serum total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for patient with total bilirubin levels \> 1.5 ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN

* Both values must be in the specified range
* Albumin \>= 2.5 g/dL
* International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
* Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
* Patients on anticoagulation or antiplatelet agents may be enrolled at the discretion of the treating physician, provided these can be safely held as needed for surgical procedures
* Anticipated life expectancy of ≥ 6 months
* Willing to comply with study procedures
* Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study and at least 9 months after the last dose of study medication
* For female patients of childbearing potential, a negative pregnancy test is required at or within 7 days prior to enrollment
* Be willing and able to understand and sign the written informed consent document
* Be willing to undergo two diagnostic laparoscopies with tumor biopsy tissue. Patients must consent to on-treatment biopsies prior to initiation of clinical trial
* Be willing to provide peripheral blood and peritoneal samples for correlative studies

Exclusion Criteria

* Patients who are receiving any other investigational drugs
* Evidence of metastatic disease other than peritoneum based on standard of care (SOC) imaging
* Patients with primary mucinous appendiceal tumors will not be eligible. These tumors often produce mucin, which may affect the penetration of IP chemotherapy. Patients with non-mucinous appendiceal adenocarcinomas will be eligible.
* Patients with \>= grade 2 peripheral neuropathy
* Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, active bleeding diatheses, and psychiatric illness/social situations that would limit compliance with study requirements
* Major surgical procedure or significant traumatic injury less than 3 weeks or those who receive minor surgical procedures within 1 week from first dose of study drug administration
* Known active chronic infections - uncontrolled human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), known active (i.e., with detectable polymerase chain reaction \[PCR\]) hepatitis B or C
* Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
* Pregnancy or breastfeeding
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating physician
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Arjun Mittra

OTHER

Sponsor Role lead

Responsible Party

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Arjun Mittra

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Arjun Mittra, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

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Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

UT Southwestern/Simmons Cancer Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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The Ohio State University Comprehensive Cancer Center

Role: CONTACT

Phone: 800-293-5066

Email: [email protected]

Facility Contacts

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Arjun Mittra, MD

Role: primary

Jennifer Knight

Role: primary

Related Links

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Other Identifiers

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NCI-2023-10497

Identifier Type: REGISTRY

Identifier Source: secondary_id

R21CA282536

Identifier Type: NIH

Identifier Source: secondary_id

View Link

OSU-23195

Identifier Type: -

Identifier Source: org_study_id