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An Open-label Phase I/II Study of KX2-391 in Combination With Paclitaxel in Patients With Advanced Solid Tumors


Phase 1/Phase 2
20 Years
N/A
Open (Enrolling)
Both
Unspecified Adult Solid Tumor, Protocol Specific, Gastric Cancer, Breast Cancer

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Trial Information

An Open-label Phase I/II Study of KX2-391 in Combination With Paclitaxel in Patients With Advanced Solid Tumors


Inclusion Criteria:



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:

1. 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)

2. Aged ≥ 20 years

3. ECOG (Eastern Cooperative Oncology Group) ≤ 2

4. Life expectancy ≥ 12 weeks

5. 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)

6. 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

7. Subjects who voluntarily consent to participate in this study and sign the written
informed consent form

Exclusion Criteria:

1. Uncontrolled central nervous system metastasis

2. Malignant ascites requiring surgical treatment

3. Subjects who have blood malignancies including leukemia; or who have received or will
receive bone marrow transplantation

4. 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

5. 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)

6. Received other investigational product within 4 weeks prior to the administration of
this study drug

7. 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)

8. History of hypersensitivity to paclitaxel, compounds with similar chemical structure,
or cremophor (polyoxyethylated castor oil) ingredient

9. Neuropathy of grade ≥ 3 based on clinical screening

10. Known history of hepatitis B or C and known history of HIV serum positive

11. Others unable to participate in the study under the judgment of the investigator

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting Toxicities (DLTs) in Phase I Portion

Outcome Description:

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

Outcome Time Frame:

From start of the treatment to end of cycle 1, which are 4 weeks

Safety Issue:

Yes

Principal Investigator

Seock-Ah Im, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Seoul National University Hospital

Authority:

Korea: Food and Drug Administration

Study ID:

HM-KXI-101

NCT ID:

NCT01764087

Start Date:

December 2012

Completion Date:

May 2016

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Gastric Cancer
  • Breast Cancer
  • Stomach Neoplasms
  • Breast Neoplasms
  • Carcinoma
  • Neoplasms
  • Paclitaxel
  • Tubulin Modulators
  • Antimitotic Agents
  • Protein Kinase Inhibitors
  • Enzyme Inhibitors
  • Pharmacologic Actions
  • Breast Neoplasms
  • Stomach Neoplasms
  • Neoplasms

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