Trial Outcomes & Findings for Exploratory Study of ART-123 for the Prevention of Cancer Treatment Related Symptoms in Patients With Postoperative Stage II / III Colon Cancer (NCT NCT02792842)

Last Updated: 2024-04-04

Results Overview

NCI-CTCAE was used for investigator-reported outcomes of peripheral sensory neuropathy; it was assessed every day from day 1 to day 3 of each cycle and on days 15 (the day after 14 days have elapsed from the date of administration) of Cycle 12 and 43 (the day after 42 days have elapsed from the date of administration of Cycle 12) of cycle 12 as follow-up assessment. Once grade 2 or higher neuropathy was observed in a certain participant, that participant was categorized as grade 2 or higher even if the grade returned to 1 or lower in subsequent cycles. Participants who discontinued the study or whose evaluation data were missing without reaching grade 2 or higher neuropathy were analyzed as no grade 2 or higher neuropathy. No primary endpoint was specified due to the exploratory nature of the study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

79 participants

Primary outcome timeframe

42 days after the start of cycle 12 (each cycle is 2 weeks).

Results posted on

2024-04-04

Participant Flow

Participant milestones

Participant milestones
Measure	ART-123 (3-day ART) ART-123 (3-day ART): ART-123 380 U/kg infusion once daily on days 1-3 in each cycle	ART-123 (1-day ART) ART-123 (1-day ART): ART-123 380 U/kg infusion once on day 1 and placebo infusion once daily on days 2-3 in each cycle	Placebo Placebo: Placebo infusion once daily on days 1-3 in each cycle
Overall Study STARTED	24	27	28
Overall Study COMPLETED	20	23	21
Overall Study NOT COMPLETED	4	4	7

Reasons for withdrawal

Reasons for withdrawal
Measure	ART-123 (3-day ART) ART-123 (3-day ART): ART-123 380 U/kg infusion once daily on days 1-3 in each cycle	ART-123 (1-day ART) ART-123 (1-day ART): ART-123 380 U/kg infusion once on day 1 and placebo infusion once daily on days 2-3 in each cycle	Placebo Placebo: Placebo infusion once daily on days 1-3 in each cycle
Overall Study Adverse Event	4	2	3
Overall Study Withdrawal by Subject	0	1	2
Overall Study Lost to Follow-up	0	0	1
Overall Study Schedule delay	0	1	1

Baseline Characteristics

Exploratory Study of ART-123 for the Prevention of Cancer Treatment Related Symptoms in Patients With Postoperative Stage II / III Colon Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ART-123 (3-day ART) n=24 Participants ART-123 (3-day ART): ART-123 380 U/kg infusion once daily on days 1-3 in each cycle	ART-123 (1-day ART) n=27 Participants ART-123 (1-day ART): ART-123 380 U/kg infusion once on day 1 and placebo infusion once daily on days 2-3 in each cycle	Placebo n=28 Participants Placebo: Placebo infusion once daily on days 1-3 in each cycle	Total n=79 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=93 Participants	9 Participants n=4 Participants	10 Participants n=27 Participants	30 Participants n=483 Participants
Age, Categorical >=65 years	13 Participants n=93 Participants	18 Participants n=4 Participants	18 Participants n=27 Participants	49 Participants n=483 Participants
Age, Continuous	66.0 years n=93 Participants	68.0 years n=4 Participants	68.0 years n=27 Participants	67.0 years n=483 Participants
Sex: Female, Male Female	13 Participants n=93 Participants	15 Participants n=4 Participants	12 Participants n=27 Participants	40 Participants n=483 Participants
Sex: Female, Male Male	11 Participants n=93 Participants	12 Participants n=4 Participants	16 Participants n=27 Participants	39 Participants n=483 Participants
Race/Ethnicity, Customized Asian	24 Participants n=93 Participants	27 Participants n=4 Participants	28 Participants n=27 Participants	79 Participants n=483 Participants

PRIMARY outcome

Timeframe: 42 days after the start of cycle 12 (each cycle is 2 weeks).

Population: The preventive effect of ART-123 on neuropathy was analyzed in all randomly assigned participants who received at least one dose of study drug and oxaliplatin and had a FACT/GOG-Ntx-12 or NCI-CTCAE evaluation at least once after oxaliplatin administration.

Outcome measures

Outcome measures
Measure	ART-123 (3-day ART) n=24 Participants ART-123 (3-day ART): ART-123 380 U/kg infusion once daily on days 1-3 in each cycle	ART-123 (1-day ART) n=27 Participants ART-123 (1-day ART): ART-123 380 U/kg infusion once on day 1 and placebo infusion once daily on days 2-3 in each cycle	Placebo n=28 Participants Placebo: Placebo infusion once daily on days 1-3 in each cycle
The Cumulative Rates of Participants With NCI-CTCAE Grade 2 or Higher Peripheral Sensory Neuropathy: Up to End of Study Treatment	11 Participants	11 Participants	18 Participants

PRIMARY outcome

Timeframe: At baseline, at each cycle (up to cycle 12 with each cycle of 2 weeks), and follow-up assessment.

Participant-reported outcomes were evaluated using the FACT/GOG-Ntx-12 version 4.0, which measured the severity and impact of symptoms of neuropathy over the past 7 days. Scores range from 0 to 48, with lower scores indicating more severe neurotoxicity. Participants completed paper questionnaires on days 1 and 8 of each cycle, on day 15 (the day after 14 days have elapsed from the date of administration) of cycle 12 and day 43 (the day after 42 days have elapsed from the date of administration) of cycle 12 as follow-up assessment. LS means were calculated from the mixed effect model for repeated measures (MMRM). Analysis included the fixed, categorical effects of study treatment, analysis visit, and study treatment-by-visit interaction. If multiple measurements occurred within the same visit, the measurement with the worst value was used. No primary endpoint was specified due to the exploratory nature of the study.

Outcome measures

Outcome measures
Measure	ART-123 (3-day ART) n=24 Participants ART-123 (3-day ART): ART-123 380 U/kg infusion once daily on days 1-3 in each cycle	ART-123 (1-day ART) n=27 Participants ART-123 (1-day ART): ART-123 380 U/kg infusion once on day 1 and placebo infusion once daily on days 2-3 in each cycle	Placebo n=28 Participants Placebo: Placebo infusion once daily on days 1-3 in each cycle
Least-squares (LS) Means of Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity-12 (FACT/GOG-Ntx-12) Version 4.0 Score at Cycle 12	32.3 score on a scale Interval 28.4 to 36.3	36.3 score on a scale Interval 32.4 to 40.1	28.9 score on a scale Interval 25.0 to 32.8

PRIMARY outcome

Timeframe: Cycle 12（each cycle is 2 weeks）

The number of people who discontinued oxaliplatin because of OIPN was counted and the percentage of the total was calculated. No primary endpoint was specified due to the exploratory nature of the study.

Outcome measures

Outcome measures
Measure	ART-123 (3-day ART) n=24 Participants ART-123 (3-day ART): ART-123 380 U/kg infusion once daily on days 1-3 in each cycle	ART-123 (1-day ART) n=27 Participants ART-123 (1-day ART): ART-123 380 U/kg infusion once on day 1 and placebo infusion once daily on days 2-3 in each cycle	Placebo n=28 Participants Placebo: Placebo infusion once daily on days 1-3 in each cycle
The Discontinuation Rate of Oxaliplatin Due to Oxaliplatin-Induced Peripheral Neuropathy (OIPN)	6 Participants	4 Participants	9 Participants

Adverse Events

ART-123 (3-day ART)

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

ART-123 (1-day ART)

Serious events: 5 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ART-123 (3-day ART) n=24 participants at risk ART-123 (3-day ART): ART-123 380 U/kg infusion once daily on days 1-3 in each cycle	ART-123 (1-day ART) n=27 participants at risk ART-123 (1-day ART): ART-123 380 U/kg infusion once on day 1 and placebo infusion once daily on days 2-3 in each cycle	Placebo n=28 participants at risk Placebo: Placebo infusion once daily on days 1-3 in each cycle
Infections and infestations Infective spondylitis	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	3.6% 1/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	4.2% 1/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	7.4% 2/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	3.7% 1/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	4.2% 1/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	3.7% 1/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Enterocolitis	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	3.7% 1/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Gastrointestinal mucosal disorder	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	3.7% 1/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
General disorders Fatigue	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	3.6% 1/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Injury, poisoning and procedural complications Femur fracture	4.2% 1/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	3.7% 1/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	3.7% 1/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date

Other adverse events

Other adverse events
Measure	ART-123 (3-day ART) n=24 participants at risk ART-123 (3-day ART): ART-123 380 U/kg infusion once daily on days 1-3 in each cycle	ART-123 (1-day ART) n=27 participants at risk ART-123 (1-day ART): ART-123 380 U/kg infusion once on day 1 and placebo infusion once daily on days 2-3 in each cycle	Placebo n=28 participants at risk Placebo: Placebo infusion once daily on days 1-3 in each cycle
Gastrointestinal disorders Nausea	37.5% 9/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	44.4% 12/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	32.1% 9/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Stomatitis	33.3% 8/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	22.2% 6/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	17.9% 5/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Constipation	16.7% 4/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	25.9% 7/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	21.4% 6/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Diarrhoea	20.8% 5/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	18.5% 5/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	17.9% 5/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Vomiting	8.3% 2/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	7.4% 2/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	14.3% 4/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Haemorrhoids	8.3% 2/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	10.7% 3/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Dyspepsia	12.5% 3/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date
Gastrointestinal disorders Abdominal pain upper	0.00% 0/24 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	0.00% 0/27 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date	7.1% 2/28 • From informed consent until the day 42 days have elapsed from the Cycle 12, with each cycle of 2 weeks, administration date

Additional Information

Contact for Clinical Trial Information

Asahi Kasei Pharma Corporation

Phone: +81-3-6699-3600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place