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

NCT06269978 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: OSU-23195NCI-2023-10497R21CA282536
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• Maximum tolerated dose (MTD)

  MTD will be determined based on isotonic regression. Specifically, the MTD will be selected as the dose for which the isotonic estimate of the toxicity rate is closest to the targeted dose limiting toxicities via Bayesian optimal interval software.

  Up to 1 year

• Incidence of adverse events

  Adverse events (AEs) will be classified and attributed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and will be summarized within and across dose levels using descriptive statistics. The overall number and percentage of patients experiencing AEs and toxicities will be summarized and reported as across all event types. All patients who have received at least one dose of the therapeutic agents will be evaluable for toxicity and tolerability.

  Up to 30 days after completion of study treatment

• Area under the curve

  Will be computed using non-compartmental and compartmental methods. Will use graphical analyses as well as repeated measure models (linear or nonlinear mixed models, generalized estimating equations) to assess the pharmacokinetic markers in relation to clinical treatment outcomes, recognizing some inherent limitations due to sample size.

  At the end of Cycle 1 (each cycle is 28 days)

• Clearance

  Will be computed using non-compartmental and compartmental methods. Will use graphical analyses as well as repeated measure models (linear or nonlinear mixed models, generalized estimating equations) to assess the pharmacokinetic markers in relation to clinical treatment outcomes, recognizing some inherent limitations due to sample size.

  At the end of Cycle 1 (each cycle is 28 days)

• Volume of distribution

  Will be computed using non-compartmental and compartmental methods. Will use graphical analyses as well as repeated measure models (linear or nonlinear mixed models, generalized estimating equations) to assess the pharmacokinetic markers in relation to clinical treatment outcomes, recognizing some inherent limitations due to sample size.

  At the end of Cycle 1 (each cycle is 28 days)

• Half-life

  Will be computed using non-compartmental and compartmental methods. Will use graphical analyses as well as repeated measure models (linear or nonlinear mixed models, generalized estimating equations) to assess the pharmacokinetic markers in relation to clinical treatment outcomes, recognizing some inherent limitations due to sample size.

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (5)

• Tumor-cell intrinsic effects in response to IP 5FU+oxaliplatin

  Up to 16 weeks

• Modulation of the tumor microenvironment in response to IP 5FU+oxaliplatin

  Up to 16 weeks

• Changes in the makeup of circulating immune cells in response to IP 5FU+oxaliplatin

  Up to 16 weeks

• Rate of conversion from unresectable to resectable

  At time of second laparoscopy, after 4 cycles of treatment (16 weeks)

• Overall response rate

  Up to 16 weeks

Study Arms (1)

Treatment (oxaliplatin, 5FU)

EXPERIMENTAL

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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Diagnostic Laparoscopy; Drug: Fluorouracil; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Procedure: Surgical Procedure

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (oxaliplatin, 5FU)

Biospecimen Collection PROCEDURE

Undergo collection of blood and IP fluid samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (oxaliplatin, 5FU)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (oxaliplatin, 5FU)

Diagnostic Laparoscopy PROCEDURE

Undergo diagnostic laparoscopy

Treatment (oxaliplatin, 5FU)

Fluorouracil DRUG

Given via IP infusion

Also known as: 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

Treatment (oxaliplatin, 5FU)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: 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

Treatment (oxaliplatin, 5FU)

Oxaliplatin DRUG

Given via IP infusion

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (oxaliplatin, 5FU)

Surgical Procedure PROCEDURE

Undergo placement of indwelling IP port

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (oxaliplatin, 5FU)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arjun Mittra: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

UT Southwestern/Simmons Cancer Center

Dallas, Texas, 75390, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Biopsy; Specimen Handling; Laparoscopy; Fluorouracil; dehydroftorafur; Magnetic Resonance Spectroscopy; Oxaliplatin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Investigative Techniques; Endoscopy; Minimally Invasive Surgical Procedures; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Coordination Complexes; Organic Chemicals

Study Officials

• Arjun Mittra, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: February 21, 2024
• Study Start: December 31, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)