A Study of KX2-391 With Paclitaxel in Patients With Solid Tumors
- Conditions
- Gastric CancerBreast CancerUnspecified Adult Solid Tumor, Protocol Specific
- Interventions
- Drug: KX2-391 and Paclitaxel
- Registration Number
- NCT01764087
- Lead Sponsor
- Hanmi Pharmaceutical Company Limited
- Brief Summary
The primary objective of this study is to determine the maximum tolerated dose (MTD) of KX2-391 in Combination with paclitaxel in Phase I, and to evaluate the efficacy of KX2-391 in combination with paclitaxel in patients who are diagnosed as gastric and breast cancer, respectively in Phase II.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 60
Phase I Portion:
- Diagnosis of solid tumors on histopathological examination or cytological examination for which no standard of care is available or conventional treatment modalities have no therapeutic effect at the time of entering into the study
Phase II Portion:
- Diagnosis of advanced/metastatic/recurrent stomach cancer or breast cancer on histopathological examination or cytological examination for which no standard of care is available or conventional treatment modalities have no therapeutic effect at the time of entering into the study
- Subjects with stomach cancer without prior taxane therapy
- Subjects with breast cancer with prior taxane therapy
- (Optional) Providing exploratory biomarker informed consent form to obtain archival tumor tissue and/or new tumor biopsy sample
Common:
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Based on clinical screening,
① If radiotherapy was given, at least 4 weeks should have passed from the last treatment date and the patient should have recovered from the toxicity (However, for limited regional radiotherapy, at least 2 weeks from the last treatment date)
② If hormonal therapy was given, at least 2 weeks should have passed from the last treatment date and the patient should have recovered from the toxicity.
③ If chemotherapy was given, at least 3 weeks should have passed from the last treatment date and the patient should have recovered from the toxicity (However, for nitrosourea or mitomycin, at least 6 weeks)
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Aged ≥ 20 years
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ECOG (Eastern Cooperative Oncology Group) ≤ 2
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Life expectancy ≥ 12 weeks
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Should meet the followings,
① Bone marrow function ANC (Absolute Neutrophil Count) ≥ 1.5 X 109/L, PLT (Platelet Count) ≥ 100 X 109/L, Hemoglobin ≥ 9.0 g/dl (In the case of hemoglobin of < 9.0 g/dl, the patient can be enrolled if the value is reversed to ≥ 9.0 g/dl.)
② Kidney function Creatinine Clearance > 50 ml/min or Serum Clearance ≤ 1.5 mg/dl
③ Liver function AST (Aspartate Aminotransferase)/ALT (Alanine Aminotransferase)/ALP (Alkaline Phosphatase) ≤ 3.0 X UNL and Total bilirubin ≤ 2.0 mg/dl (With bone metastasis, ALP ≤ 5.0 X UNL)
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At least one measurable lesions with the length of the longest diameter of ≥ 10 mm on spiral CT or multidetector CT or ≥ 20 mm on conventional CT
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Subjects who voluntarily consent to participate in this study and sign the written informed consent form
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Uncontrolled central nervous system metastasis
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Malignant ascites requiring surgical treatment
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Subjects who have blood malignancies including leukemia; or who have received or will receive bone marrow transplantation
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Severe concurrent diseases as follows,
① History of unstable angina, heart failure, atrial or ventricular arrhythmia requiring pharmacological treatment, or having received treatment for myocardial infarction within 6 months (however, may be included under the judgment of the investigator if medically controlled), heart failure of Class III or IV by New York Heart Association Classes, or left ventricular ejection fraction of < 40%
② Receiving therapeutic dose administration of coumarin-type anticoagulants (however, up to 2 mg daily is permitted for line opening)
③ Uncontrolled diabetes (fasting plasma glucose > 2.0 X UNL), severe hypertension, thyroid disorder and active infectious disease
④ Psychiatric or neurological history including dementia or epilepsy which may threaten the compliance with this protocol
⑤ A condition not allowing oral application of tablet formulation, and any clinically significant gastrointestinal abnormalities which may interfere with taking, passing or absorption of the study drug
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Using disallowed concomitant medications (strong CYP3A4 (Cytochrome P450 3A4) inhibitors or inducers) (When a patient is using any of the disallowed concomitant medications below, wash-out of 1 week from the medication date is required)
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Received other investigational product within 4 weeks prior to the administration of this study drug
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Pregnant or breast-feeding women (however, women with 12 months of natural (spontaneous) amenorrhea or surgical bilateral oophorectomy (alone or with hysterectomy) at least 6 weeks ago, with appropriate clinical profile (e.g., appropriate age, history of vasomotor symptoms), will be considered women postmenopausal and of non-childbearing potential. In the case of oophorectomy alone, a woman will be considered to be of non-childbearing potential only if her reproductive condition is confirmed by follow-up hormone level assessment)
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History of hypersensitivity to paclitaxel, compounds with similar chemical structure, or cremophor (polyoxyethylated castor oil) ingredient
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Neuropathy of grade ≥ 3 based on clinical screening
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Known history of hepatitis B or C and known history of HIV serum positive
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Others unable to participate in the study under the judgment of the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description KX2-391 and Paclitaxel KX2-391 and Paclitaxel The phase I portion is a standard, three-patient per cohort, dose escalation schedule will be used. 3 or 6 subjects with solid tumor per dose group will likely be necessary to determine the MTD of KX2-391 in combination with weekly paclitaxel. With paclitaxel dose fixed at 80 mg/m2/weekly, KX2-391 treatment will be started at 20 mg dose once daily (QD) The phase II portion of this trial has a design to determine the efficacy of KX2-391 when administered in combination with paclitaxel in 20 subjects with stomach cancer and 20 subjects with breast cancer
- Primary Outcome Measures
Name Time Method Dose-limiting Toxicities (DLTs) in Phase I Portion From start of the treatment to end of cycle 1, which are 4 weeks Maximum tolerated dose (MTD) of KX2-391 in combination with weekly paclitaxel as determined by number of participants With DLTs related to KX2-391 in combination with weekly paclitaxel
Tumor Overall Response Rates (ORRs) in Phase II Portion In every 2 cycles up to end of the treatment, an expected average of 16 weeks The efficacy (overall response rate; ORR; complete response (CR) + partial response (PR)) of KX2-391 in combination with weekly paclitaxel at the MTD established during the phase I portion of this trial based on Response Evaluation Criteria in Solid Tumor (RECIST) 1.1
- Secondary Outcome Measures
Name Time Method The Preliminary Efficacy Data in Phase I Portion In every 2 cycles up to end of the treatment, an expected average of 8 weeks The preliminary efficacy of KX2-391 in combination with weekly paclitaxel as determined by ORRs based on RECIST 1.1
Safety in Phase II Portion From start of the treatment to end of the treatment, an expected average of 16 weeks Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECG change monitoring as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03
The Efficacy Data in Phase II Portion Up to die, an expected average of 24 weeks Overall survival (OS), progression free survival (PFS), time to tumor progression (TTP) and duration of response
Pharmacokinetic (PK) Evaluation in Phase I Portion Time points at day 0, 1 and 8 in cycle 1 PK parameters, including but not limited to, plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2 of KX2-391 alone and in combination with weekly paclitaxel
Pharmacokinetic (PK) Evaluation in Phase II Portion Time points at day 1 and 8 in cycle 1 PK parameters, including but not limited to, plasma concentration, AUC0-t, Cmax, Tmax, and T1/2 of KX2-391 alone and in combination with weekly paclitaxel
Trial Locations
- Locations (2)
Seoul National University Bundang Hospital
🇰🇷Seongnam, Gyeonggi-Do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of