Postoperative Stage II/III Colon Cancer
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of ART-123 for the prevention of cancer treatment related symptoms in patients with postoperative stage II / III colon cancer.
Interventions
DRUGART-123 (3-day ART)
ART-123 380 U/kg infusion once daily on days 1-3 in each cycle
DRUGART-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
DRUGPlacebo
Placebo infusion once daily on days 1-3 in each cycle
Sponsors
Asahi Kasei Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Diagnosed with stage II / III colon cancer * Deemed to have undergone curative A (Cur A) surgery * Planning to undergo postoperative adjuvant chemotherapy Main
Exclusion criteria
* Have a history of hypersensitivity to any of the ingredients in thrombomodulin alfa (recombinant) * Have any treatment history of systemic chemotherapy (including any drug in the clinical trial stage) or radiotherapy * With active double cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Cumulative Rates of Participants With NCI-CTCAE Grade 2 or Higher Peripheral Sensory Neuropathy: Up to End of Study Treatment | 42 days after the start of cycle 12 (each cycle is 2 weeks). | 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. |
| 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 | 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. |
| The Discontinuation Rate of Oxaliplatin Due to Oxaliplatin-Induced Peripheral Neuropathy (OIPN) | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 24 |
| 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 | 27 |
| Placebo Placebo: Placebo infusion once daily on days 1-3 in each cycle | 28 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Schedule delay | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | ART-123 (1-day ART) | Placebo | ART-123 (3-day ART) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 18 Participants | 13 Participants | 49 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 11 Participants | 30 Participants |
| Age, Continuous | 68.0 years | 68.0 years | 66.0 years | 67.0 years |
| Race/Ethnicity, Customized Asian | 27 Participants | 28 Participants | 24 Participants | 79 Participants |
| Sex: Female, Male Female | 15 Participants | 12 Participants | 13 Participants | 40 Participants |
| Sex: Female, Male Male | 12 Participants | 16 Participants | 11 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 27 | 0 / 28 |
| other Total, other adverse events | 24 / 24 | 27 / 27 | 28 / 28 |
| serious Total, serious adverse events | 3 / 24 | 5 / 27 | 2 / 28 |
Outcome results
Primary
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
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.
Time frame: At baseline, at each cycle (up to cycle 12 with each cycle of 2 weeks), and follow-up assessment.
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ART-123 (3-day ART) | 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 |
| ART-123 (1-day ART) | 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 | 36.3 score on a scale |
| Placebo | 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 | 28.9 score on a scale |
Primary
The Cumulative Rates of Participants With NCI-CTCAE Grade 2 or Higher Peripheral Sensory Neuropathy: Up to End of Study Treatment
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ART-123 (3-day ART) | The Cumulative Rates of Participants With NCI-CTCAE Grade 2 or Higher Peripheral Sensory Neuropathy: Up to End of Study Treatment | 11 Participants |
| ART-123 (1-day ART) | The Cumulative Rates of Participants With NCI-CTCAE Grade 2 or Higher Peripheral Sensory Neuropathy: Up to End of Study Treatment | 11 Participants |
| Placebo | The Cumulative Rates of Participants With NCI-CTCAE Grade 2 or Higher Peripheral Sensory Neuropathy: Up to End of Study Treatment | 18 Participants |
Primary
The Discontinuation Rate of Oxaliplatin Due to Oxaliplatin-Induced Peripheral Neuropathy (OIPN)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ART-123 (3-day ART) | The Discontinuation Rate of Oxaliplatin Due to Oxaliplatin-Induced Peripheral Neuropathy (OIPN) | 6 Participants |
| ART-123 (1-day ART) | The Discontinuation Rate of Oxaliplatin Due to Oxaliplatin-Induced Peripheral Neuropathy (OIPN) | 4 Participants |
| Placebo | The Discontinuation Rate of Oxaliplatin Due to Oxaliplatin-Induced Peripheral Neuropathy (OIPN) | 9 Participants |