Evaluate Oral Topotecan With HM30181A Monotherapy in Patients With Advanced Malignancies

Study Overview
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Brief Summary
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This is a multicenter, nonrandomized, open-label, safety, tolerability and pharmacokinetic (PK) study to determine the MTD and optimal dosing of Oratopo. No control group has been included.

Detailed Description
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This is a multicenter, open-label, safety, tolerability, pharmacokinetic, and activity study. Eligible subjects will be adults with advanced solid tumor malignancies. In the treatment period groups of 3 to 6 subjects will receive a single dose of oral Oratopo will be administered and will be followed for toxicity. Dose escalation will continue until an MTD is reached, or nonlinear increases in exposure are confirmed, or a maximum dose of Oratopo is reached.

Official Title
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A Dose Regimen-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of Oral Topotecan With HM30181A Monotherapy in Patients With Advanced Malignancies

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: Oratopo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Male and female adults ≥18 years of age Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective Topotecan monotherapy is a reasonable treatment in the judgement of the Investigator Measurable disease as per RECIST v1.1 criteria Able to swallow oral medication as an intact dosage form Adequate hematologic status as demonstrated by not requiring transfusion support or granulocyte colony-stimulating factor (G-CSF)levels maintained Adequate liver function. Adequate renal function Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Life expectancy of at least 3 months Females must be postmenopausal (>12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or, if sexually active, must be using effective contraception (ie, oral contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for 30 days after their last dose of study drug. Sexually active male patients must use a barrier method of contraception during the study and agree to continue the use of male contraception for at least 30 days after the last dose of study drug. Exclusion Criteria: Currently taking a prohibited concomitant medication, other than a premedication, that are Strong inhibitors or strong inducers of cytochrome P450 Unresolved toxicity from prior chemotherapy Planning to receive other medical, surgical, or radiological cancer treatments during the course of this study Received investigational agents within 14 days or 5 half-lives prior to the first study dosing day, whichever is longer Require therapeutic use of anticoagulants. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant myocardial infarction unstable angina pectoris, clinically significant cardiac arrhythmia, bleeding disorder, chronic pulmonary disease requiring oxygen, or psychiatric illness/social situations that would limit compliance with study requirements. Major surgery to the upper GI tract Hypersensitivity to topotecan or allergy to HM30181A or its excipients. Any other condition which the Investigator believes would make participation in the study not acceptable

Ages Eligible for Study
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Minimum Age: 18 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: Oratopo<br>To determine the Maximum Tolerated Dose (MTD) of oral topotecan with HM30181A administered once daily for 5 consecutive days every 21 days. | Drug: Oratopo<br>* Oral topotecan will be supplied in topotecan capsules and oral HM30181A-US tablets<br>* Other names: oral topotecan + oral HM30181A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Maximum Tolerated Dose (MTD) | dose limiting toxicities occuring in the first cycle of therapy | Day 1 through 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessment using Adverse Events of Oratopo | Safety assessment using Adverse Events of Oratopo | Weekly, from randomization throughout the study for approximately 24 months | 
| Pharmacokinetics of Oratopo | Plasma concentrations of Oratopo | At the end of Cycle 1 (each cycle is 21 days) |