Phase I of OratecanTM in Combination With Capecitabine in Patients With Advanced Solid Malignancies

Study Overview
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Brief Summary
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The main objective of this study is to determine the maximum tolerated dose (MTD) of Oratecan in combination with capecitabine

Detailed Description
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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

Official Title
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A Phase I Clinical Trial to Determine the Maximum Tolerated Dose and to Assess the Safety of OratecanTM in Combination With Capecitabine in Patients With Advanced Solid Cancer

Conditions
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Solid Tumor, Advanced Cancer

Intervention / Treatment
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* Drug: Oratecan and Capecitabine


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oratecan and Capecitabine<br>Oratecan(HM30181AK + Irinotecan HCl) and 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 | Drug: Oratecan and Capecitabine<br>* 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<br>* Other names: Oratecan(HM30181AK + Irinotecan HCl) and Capecitabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Cycle 1 (21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | tumor response evaluation can continue to receive the study drug until PD confirmation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid cancer