Advanced Cancer, Solid Tumor
Conditions
Keywords
Advanced solid cancer
Brief summary
The main objective of this study is to determine the maximum tolerated dose (MTD) of Oratecan in combination with capecitabine
Detailed description
Besides the main objective, there are 4 other objectives as follows: * To assess the safety of Oratecan in combination with capecitabine * To evaluate anticancer activity of Oratecan in combination with capecitabine in patients with advanced solid malignancies * To characterize the pharmacokinetics of Oratecan and its metabolites following oral administration of OratecanTM in combination with capecitabine
Interventions
DRUGOratecan and Capecitabine
Oratecan in combination with Capecitabine * Irinotecan HCl Tablet - Initial dose 10 mg/m2 (may be increased up to 20 mg/m2), Day1\ Day5 * HM30181AK Tablet - Fixed dose 15 mg, Day1\ Day5 * Capecitabine Tablet - Initial dose 800 mg/m2 (may be increased up to 1000 mg/m2), Day1\ Day14
Sponsors
Hanmi Pharmaceutical Company Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed advanced solid tumor * Patients who have experienced progressive disease despite of conventional anticancer therapy. Patients who cannot expect effective treatment or prolonged survival with conventional anticancer therapy * Previous chemotherapy, radiotherapy and surgical operation are allowed if they are discontinued for at least 4 weeks prior to D0 and all adverse events are resolved * Aged ≥19 * Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2 * A life expectancy greater than 12 weeks * Adequate bone marrow, renal and liver function. * Subjects must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures
Exclusion criteria
* Patients with hematopoietic malignancies,uncontrolled infection, CNS metastasis. * Patients who have undergone hematopoietic stem cell transplantation (HSCT) or are candidates for planned HSCT * Patients who have GI malabsorption or difficulty taking oral medication * Patients who have psychiatric or congenital disorder Subjects who, in the investigator's opinion, cannot be treated per protocol due to functional impairments * Pregnant or breast-feeding patients; Women of childbearing potential without adequate contraception (Men must use adequate contraception.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity Assessment and Maximum Tolerated Dose Determination | Cycle 1 (21 days) | If Dose Limiting Toxicity(DLT) was not observed in the third subject at a dose level from the first study drug dosing date (Day 1) to the end of Cycle 1(21 days), increase the dose to the next level and enroll subjects; enrollment up to Level 4 was allowed. (NCI-CTCAE version 3.0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | tumor response evaluation can continue to receive the study drug until PD confirmation | by RECIST guideline Objective response rate = (Number of subjects with best overall response as confirmed CR or PR / Total number of subjects)\*100. Response rate = (Number of subjects with best overall response as CR or PR / Total number of subjects)\*100. Disease control rate = (Number of subjects with best overall response as confirmed CR or PR or SD / Total number of subjects)\*100. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine 800mg/㎡ + Oratecan 10mg/㎡ One cycle was composed of 3 weeks. Oratecan™ was administered once daily for 5 consecutive days, and Capecitabine Tablet was administered twice daily for 14 consecutive days, followed by washout period for 7 days. | 3 |
| Capecitabine 800mg/㎡ + Oratecan 15mg/㎡ One cycle was composed of 3 weeks. Oratecan™ was administered once daily for 5 consecutive days, and Capecitabine Tablet was administered twice daily for 14 consecutive days, followed by washout period for 7 days. | 8 |
| Capecitabine 800mg/㎡ + Oratecan 20mg/㎡ One cycle was composed of 3 weeks. Oratecan™ was administered once daily for 5 consecutive days, and Capecitabine Tablet was administered twice daily for 14 consecutive days, followed by washout period for 7 days. | 4 |
| Capecitabine 1000mg/㎡ + Oratecan 15mg/㎡ One cycle was composed of 3 weeks. Oratecan™ was administered once daily for 5 consecutive days, and Capecitabine Tablet was administered twice daily for 14 consecutive days, followed by washout period for 7 days. | 6 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Treatment delay over 5 week | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Capecitabine 800mg/㎡ + Oratecan 10mg/㎡ | Capecitabine 800mg/㎡ + Oratecan 15mg/㎡ | Capecitabine 800mg/㎡ + Oratecan 20mg/㎡ | Capecitabine 1000mg/㎡ + Oratecan 15mg/㎡ | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 6.5 | 59.5 years STANDARD_DEVIATION 9.6 | 63.8 years STANDARD_DEVIATION 11.1 | 61.8 years STANDARD_DEVIATION 11.5 | 61.5 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment Korea, Republic of | 3 participants | 8 participants | 4 participants | 6 participants | 21 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 8 / 8 | 4 / 4 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 1 / 8 | 1 / 4 | 0 / 6 |
Outcome results
Primary
Dose Limiting Toxicity Assessment and Maximum Tolerated Dose Determination
If Dose Limiting Toxicity(DLT) was not observed in the third subject at a dose level from the first study drug dosing date (Day 1) to the end of Cycle 1(21 days), increase the dose to the next level and enroll subjects; enrollment up to Level 4 was allowed. (NCI-CTCAE version 3.0)
Time frame: Cycle 1 (21 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine 800mg/㎡ + Oratecan 10mg/㎡ | Dose Limiting Toxicity Assessment and Maximum Tolerated Dose Determination | 0.0 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 15mg/㎡ | Dose Limiting Toxicity Assessment and Maximum Tolerated Dose Determination | 0.0 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 20mg/㎡ | Dose Limiting Toxicity Assessment and Maximum Tolerated Dose Determination | 50.0 percentage of participants |
| Capecitabine 1000mg/㎡ + Oratecan 15mg/㎡ | Dose Limiting Toxicity Assessment and Maximum Tolerated Dose Determination | 0.0 percentage of participants |
Secondary
Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR)
by RECIST guideline Objective response rate = (Number of subjects with best overall response as confirmed CR or PR / Total number of subjects)\*100. Response rate = (Number of subjects with best overall response as CR or PR / Total number of subjects)\*100. Disease control rate = (Number of subjects with best overall response as confirmed CR or PR or SD / Total number of subjects)\*100.
Time frame: tumor response evaluation can continue to receive the study drug until PD confirmation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine 800mg/㎡ + Oratecan 10mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Objective Response rate | 0.0 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 10mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Disease Control Rate | 66.7 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 10mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Response Rate | 0.0 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 15mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Objective Response rate | 0.0 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 15mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Disease Control Rate | 42.9 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 15mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Response Rate | 0.0 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 20mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Response Rate | 0.0 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 20mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Objective Response rate | 0.0 percentage of participants |
| Capecitabine 800mg/㎡ + Oratecan 20mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Disease Control Rate | 100 percentage of participants |
| Capecitabine 1000mg/㎡ + Oratecan 15mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Objective Response rate | 33.3 percentage of participants |
| Capecitabine 1000mg/㎡ + Oratecan 15mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Disease Control Rate | 50.0 percentage of participants |
| Capecitabine 1000mg/㎡ + Oratecan 15mg/㎡ | Objective Response Rate (ORR), Response Rate (RR) and Disease Control Rate (DCR) | Response Rate | 33.3 percentage of participants |