Intraperitoneal Oxaliplatin in Combo w IV mFOLFIRI for Peritoneal Carcinomatosis From Colorectal & Appendiceal Cancer

NCT04158349 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: HCI126164
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, multi-center, open-label phase I trial designed to determine the maximun tolerated dose of IP oxaliplatin when given in combination with mFOLFIRI.

Conditions

Colorectal Cancer; Appendiceal Cancer; Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Assess the maximum tolerated dose of intraperitoneal (IP) oxaliplatin with systemic IV 5-fluorouracil, leucovorin, and irinotecan (mFOLFIRI) every 2 weeks in patients with unresectable peritoneal carcinomatosis of colorectal or appendiceal origin

  The incidence of DLTs during the defined DLT period

  One Cycle is 14 days. The DLT evaluation period will be defined as the first three cycles of combination treatment (from cycle one day one to the last day of cycle three (42days)

Secondary Outcomes (3)

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment and the IP catheter will be measured.

  up to 3 years

• The efficacy of IP oxaliplatin plus systemic mFOLFIRI in patients with peritoneal carcinomatosis of colorectal or appendiceal origin will be measured.

  up to 3 years

• The efficacy of IP oxaliplatin plus systemic mFOLFIRI in patients with peritoneal carcinomatosis of colorectal or appendiceal origin will be measured.

  Up to 3 years

Study Arms (3)

Dose Level 0

EXPERIMENTAL

Dose Level 0: 85 mg/m2 Oxaliplatin IP every 2 weeks

Drug: Oxaliplatin; Drug: mFOLFIRI

Dose Level 1

EXPERIMENTAL

Dose Level 1: 95 mg/m2 Oxaliplatin IP every 2 weeks

Drug: Oxaliplatin; Drug: mFOLFIRI

Dose Level 2

EXPERIMENTAL

Dose Level 2: 105 mg/m2 Oxaliplation IP every 2 weeks

Drug: Oxaliplatin; Drug: mFOLFIRI

Interventions

Oxaliplatin DRUG

Subjects will be accrued in cohorts of 3 to 6 subjects per dose level starting at Dose Level 0 (85 mg/m2). Escalation will continue as described in the protocol until DLT stopping rules are met or the highest dose level is reached.

Dose Level 0; Dose Level 1; Dose Level 2

mFOLFIRI DRUG

mFOLFIRI is a standardized chemotherapy regimen utilizing 5-fluorouracil, leucovorin, and irinotecan administered on day one of a 14-day cycle. 5-Fluorouracil, leucovorin, and irinotecan should be prepared and administered per the package insert and local institutional guidelines.

Dose Level 0; Dose Level 1; Dose Level 2

Eligibility Criteria

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

You may qualify if:

• Male or female subject aged ≥ 18 years.
• Histopathologically or cytologically confirmed unresectable colon, rectal or appendiceal adenocarcinoma with synchronous or metachronous (defined as occurring \> 6 months after initial diagnosis) peritoneal dissemination of disease. (Stage IV peritoneal-based disease only)
• Patient has active, measurable disease as defined by RECIST 1.1 and assessed by either abdominal CT/MRI.
• Patients must be willing and able as assessed the treating investigator to undergo placement of an IP catheter and a Port-A Cath, if not already present.
• Patients must have known satisfactory cardiopulmonary function as assessed by the treating investigator.
• ECOG Performance Status ≤ 2.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) \> 1200/mm3
• Platelet count \> 100,000/mm3
• Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN
• Coagulation:
• International normalized ratio (INR) ≤ 1.5

You may not qualify if:

• Sensory neuropathy \> grade 1 from prior therapy.
• Known low or absent Dipyrimidine Dehydrogenase (DPD) activity.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Patients with metastases outside the peritoneal cavity.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Other clinically significant disorders that would preclude safe study participation.
• Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
• Note: Patients on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
• Known chronic hepatitis B virus (HBV) or hepatitis C virus infection with a detectable viral load.
• Note: Patients with an undetectable HBV viral load on appropriate suppressive therapy are eligible. Patients with an undetectable HCV viral load on appropriate treatment are eligible.
• Live vaccinations, except flu and COVID within 4 weeks of cycle one day one and while on trial.
• Known prior severe hypersensitivity to platinum compounds, any of the investigational medication or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
• Subjects taking prohibited medications as described in Section 6.4.2. A washout period of prohibited medications for a period of at least 5 half-lives or 4 weeks, whichever is shorter, should occur prior to the start of treatment.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Appendiceal Neoplasms

Interventions

Oxaliplatin

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; Cecal Neoplasms; Cecal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Laura Lambert, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a prospective, multi-center, open-label phase I trial designed to determine the MTD of IP oxaliplatin when given in combination with mFOLFIRI. This will be conducted according to a traditional 3+3 dose-escalation schedule and halted once MTD is established.

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 8, 2019
• Study Start: March 22, 2021
• Primary Completion: May 14, 2021
• Study Completion: May 14, 2021
• Last Updated: September 27, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)