Trial Outcomes & Findings for 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 (NCT NCT00645710)

Last Updated: 2019-03-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

16 participants

Primary outcome timeframe

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

Results posted on

2019-03-28

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 1- FUdR 0.10 mg/kg/Day Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.10 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 2 - FUdR 0.15 mg/kg/Day Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.15 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 3 - FUdR 0.20 mg/kg/Day Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.20 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.
Overall Study STARTED	3	3	10
Overall Study COMPLETED	3	3	10
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 - FUdR 0.10 mg/kg/Day n=3 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (starting dose level 0.10 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 2 - FUdR 0.15 mg/kg/Day n=3 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (starting dose level 0.15 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 3 - FUdR 0.20 mg/kg/Day n=10 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (starting dose level 0.20 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Total n=16 Participants Total of all reporting groups
Age, Continuous	60 years n=5 Participants	54 years n=7 Participants	53 years n=5 Participants	56 years n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants	16 participants n=4 Participants
Karnofsky Performance Status for Assessment of Functional Impairment	90 units on a scale n=5 Participants	90 units on a scale n=7 Participants	90 units on a scale n=5 Participants	90 units on a scale n=4 Participants

PRIMARY outcome

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

Population: All patients receiving treatment were evaluated for DLT.

Outcome measures

Outcome measures
Measure	Dose Level 1- FUdR 0.10 mg/kg/Day n=3 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.10 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 2 - FUdR 0.15 mg/kg/Day n=3 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.15 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 3 - FUdR 0.20 mg/kg/Day n=10 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.20 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.
Number of Participants With at Least One Dose Limiting Toxicity	0 participants with DLTs	0 participants with DLTs	1 participants with DLTs

PRIMARY outcome

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

Population: All patients observed for 56 days while receiving a full course of therapy or who experienced a DLT. Patients withdrawing before completion of the first course, for reasons other than DLT, were replaced.

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.

Outcome measures

Outcome measures
Measure	Dose Level 1- FUdR 0.10 mg/kg/Day n=10 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.10 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 2 - FUdR 0.15 mg/kg/Day Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.15 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 3 - FUdR 0.20 mg/kg/Day Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.20 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.
Recommended Phase II Dose	0.20 mg/kg/day	—	—

SECONDARY outcome

Timeframe: Up to 5 years

Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause.

Outcome measures

Outcome measures
Measure	Dose Level 1- FUdR 0.10 mg/kg/Day n=3 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.10 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 2 - FUdR 0.15 mg/kg/Day n=3 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.15 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 3 - FUdR 0.20 mg/kg/Day n=10 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.20 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.
Overall Survival	23.2 Months Interval 18.9 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	73.2 Months Interval 27.4 to 132.9	41.2 Months Interval 18.4 to 65.5

SECONDARY outcome

Timeframe: Up to 5 years

Estimated using the product-limit method of Kaplan and Meier. Progression is defined as a 25% increase in the sum of products of measurable lesions over the smallest sum observed, or appearance of any lesions that had disappeared, or appearance of any new lesion/site.

Outcome measures

Outcome measures
Measure	Dose Level 1- FUdR 0.10 mg/kg/Day n=3 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.10 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 2 - FUdR 0.15 mg/kg/Day n=3 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.15 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 3 - FUdR 0.20 mg/kg/Day n=10 Participants Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (dose level 0.20 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.
Progression-free Survival	8.3 Months Interval 5.0 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	11.5 Months Interval 6.6 to 12.9	9.6 Months Interval 1.0 to 19.0

Adverse Events

Dose Level 1- FUdR 0.10 mg/kg/Day

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Dose Level 2- FUdR 0.15 mg/kg/Day

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

Dose Level 3- FUdR 0.20 mg/kg/Day

Serious events: 2 serious events

Other events: 10 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1- FUdR 0.10 mg/kg/Day n=3 participants at risk Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (starting dose level 0.10 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 2- FUdR 0.15 mg/kg/Day n=3 participants at risk Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (starting dose level 0.15 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.	Dose Level 3- FUdR 0.20 mg/kg/Day n=10 participants at risk Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 (starting dose level 0.20 mg/kg/day) and gemcitabine hydrochloride IV (105 mg/m\^2) over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV (16.6 mCi/m\^2) 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.
Gastrointestinal disorders Ear, nose and throat examination abnormal	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 1/10 • Number of events 1 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Mucositis oral	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 1/10 • Number of events 1 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral pain	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 1/10 • Number of events 1 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fever	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 1 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/10 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 1/10 • Number of events 1 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 1/10 • Number of events 2 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypotension	0.00% 0/3 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 1 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/10 • Adverse events were collected over a period of 6 years and 11 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Other adverse events

Additional Information

Paul Frankel, Ph.D.

City of Hope

Phone: 626-218-5265

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place