Hepatic Arterial Infusion of Floxuridine, Gemcitabine Hydrochloride, and Radiolabeled Monoclonal Antibody Therapy in Treating Liver Metastases in Patients With Metastatic Colorectal Cancer Previously Treated With Surgery

NCT00645710 | Completed Phase 1 Results DMC

• 3 other identifiers: 04122NCI-2010-01229CDR0000590335
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as floxuridine and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hepatic arterial infusion uses a catheter to carry cancer-killing substances directly into the liver. Radiolabeled monoclonal antibodies can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving hepatic arterial infusion of floxuridine together with gemcitabine hydrochloride and radiolabeled monoclonal antibody therapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase I/II trial is studying the side effects and best dose of floxuridine when given as a hepatic arterial infusion together with gemcitabine hydrochloride and radiolabeled monoclonal antibody therapy and to see how well it works in treating liver metastases in patients with metastatic colorectal cancer.

Conditions

Liver Metastases; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With at Least One Dose Limiting Toxicity

  Dose Limiting Toxicity (DLT) defined as any treatment-related grade grade 3 nonhematologic toxicity not reversible to grade 2 or less within 24 hours, or any grade 4 toxicity.Up to three cycles of therapy were allowed with DLTs determined based on first cycle tolerance. Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2.0.

  4 weeks from start of treatment, up to 2 years.

• Recommended Phase II Dose

  The maximum tolerated dose (MTD) of HAI FUdR in combination with intravenous gemcitabine and 90Y-DTPA-cT84.66 is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.

  4 weeks from start of treatment, up to 2 years.

Secondary Outcomes (2)

• Overall Survival

  Up to 5 years

• Progression-free Survival

  Up to 5 years

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV over 25 minutes on day 9. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may receive an additional course of floxuridine in combination with systemic therapy at the discretion of the treating physician.

Drug: gemcitabine hydrochloride; Drug: floxuridine; Genetic: proteomic profiling; Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry; Other: liquid chromatography; Radiation: yttrium Y 90 anti-CEA monoclonal antibody cT84.66; Other: laboratory biomarker analysis; Other: mass spectrometry; Other: pharmacological study

Interventions

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar, LY-188011

Arm I

floxuridine DRUG

Given via hepatic arterial infusion

Also known as: 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR

Arm I

proteomic profiling GENETIC

Correlative studies

Arm I

matrix-assisted laser desorption/ionization time of flight mass spectrometry OTHER

Correlative studies

Also known as: MALDI-TOF Mass Spectrometry

Arm I

liquid chromatography OTHER

Correlative studies

Also known as: LC

Arm I

yttrium Y 90 anti-CEA monoclonal antibody cT84.66 RADIATION

Given IV

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

mass spectrometry OTHER

Correlative studies

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a Karnofsky performance status of \>= 60%; this must be met pre-surgery and pre-study therapy
• Patients must have histological confirmation of colorectal carcinoma and present with potentially resectable or abatable metachronous or synchronous hepatic metastases
• Patients must have colorectal tumors that produce CEA as documented by either immunohistochemistry or by an elevated serum CEA
• Prior radiotherapy, immunotherapy, or chemotherapy must have been completed at least four weeks prior to start of FUdR/RIT therapy on this study (6 weeks if mitomycin-C or nitrosoureas were part of last therapy) and patients must have recovered from all expected side effects of the prior therapy
• Laboratory values must be met pre-surgery and pre-study therapy
• Hemoglobin \> 10 gm % (patients may be transfused to reach a hemoglobin \> 10 gm %)
• WBC \> 4000/ul
• Absolute granulocyte count of \> 1,500/mm\^3
• Platelets \> 150,000/ul
• Patients may have history of prior malignancy for which the patient has been disease-free for five years with the exception of basal or squamous cell skin cancers or carcinoma in situ of the cervix
• Patients must have no prior history of radiation therapy to the liver
• Total bilirubin \< 1.5 (unless reversibly obstructed due to the metastatic tumor)
• Serum creatinine of \< 2.0
• Patients must have evidence of intrahepatic metastases involving \< 60% of the functioning liver
• Patients cannot have evidence of extrahepatic disease with the following exceptions: patients known to have a resectable "anastomotic" or local recurrence of their tumor; patients who undergoing their initial surgery for resection of their primary colorectal carcinoma can have potentially resectable porta hepatis and/or mesenteric lymph node involvement in addition to liver metastases; patients who have disease extension from the liver metastasis that can be resected en bloc (e.g., diaphragm, kidney, and abdominal wall); patients who have minimal, potentially resectable to less than 3 cm extrahepatic disease

You may not qualify if:

• Patients that have received radiation therapy to greater than 50% of their bone marrow
• Patients with any nonmalignant intercurrent illness (example cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment or which is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible
• Biopsy-proven chronic active hepatitis

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Gemcitabine; Floxuridine; Chromatography, Liquid; Mass Spectrometry

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; 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)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyuridine; Uridine; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chromatography; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Jeffrey Wong

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: March 28, 2008
• Study Start: February 11, 2005
• Primary Completion: February 7, 2018
• Study Completion: February 7, 2018
• Last Updated: March 28, 2019
• Results First Posted: March 28, 2019

Record last verified: 2019-02

Locations

US (1)