A Study of KX2-391 With Paclitaxel in Patients With Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Hanmi Pharmaceutical Company Limited
Sponsor:
Information provided by (Responsible Party):
Hanmi Pharmaceutical Company Limited
ClinicalTrials.gov Identifier:
NCT01764087
First received: January 2, 2013
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Gastric Cancer
Breast Cancer
Drug: KX2-391 and Paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Phase I/II Study of KX2-391 in Combination With Paclitaxel in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Hanmi Pharmaceutical Company Limited:

Primary Outcome Measures:
  • Dose-limiting Toxicities (DLTs) in Phase I Portion [ Time Frame: From start of the treatment to end of cycle 1, which are 4 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: In every 2 cycles up to end of the treatment, an expected average of 16 weeks ] [ Designated as safety issue: No ]
    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 RECIST (Response Evaluation Criteria in Solid Tumor) 1.1


Secondary Outcome Measures:
  • Pharmacokinetic (PK) Evaluation in Phase I Portion [ Time Frame: Time points at day 0, 1 and 8 in cycle 1 ] [ Designated as safety issue: No ]
    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

  • The Preliminary Efficacy Data in Phase I Portion [ Time Frame: In every 2 cycles up to end of the treatment, an expected average of 8 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: From start of the treatment to end of the treatment, an expected average of 16 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to die, an expected average of 24 weeks ] [ Designated as safety issue: No ]
    Overall survival (OS), progression free survival (PFS), time to tumor progression (TTP) and duration of response

  • Pharmacokinetic (PK) Evaluation in Phase II Portion [ Time Frame: Time points at day 1 and 8 in cycle 1 ] [ Designated as safety issue: No ]
    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


Other Outcome Measures:
  • Pharmacodynamic (PD) Evaluation in Phase I Portion [ Time Frame: Time points at day 0 and 1 in cycle 1 ] [ Designated as safety issue: No ]
    Pre-dose and post-dose tubulin inhibition in peripheral blood monocytes extracted from blood samples, as measured by immunofluorescence staining

  • Exploratory Biomarker Evaluation in Phase II Portion [ Time Frame: Time points at day -6 and day 0 ] [ Designated as safety issue: No ]
    Pre-dose and post-dose Src signaling inhibition (p-Src and Ki-67) in archival tumor tissue and new biopsy sample, as measured by immunohistochemistry


Estimated Enrollment: 60
Study Start Date: December 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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

Drug: KX2-391 and Paclitaxel

A treatment cycle in phase I will consist of 28 days, according to the following schedule:

KX2-391 20 mg PO once daily, Weekly paclitaxel 80 mg/m2 given intravenously over 1 hour on day 1, 8, and 15 of a 28 day cycle.

The trial will initially test the combination of weekly paclitaxel and KX2-391 given PO, once daily , continuously. In case of 2 dose-limiting toxicities (DLT) in the first cohort, this intervention will be terminated

A treatment cycle in phase II will consist of 28 days, according to the following schedule:

KX2-391 MTD PO once daily, Weekly paclitaxel 80 mg/m2 given intravenously over 1 hour on day 1, 8, and 15 of a 28 day cycle.

Other Names:
  • KX01
  • Taxol

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01764087

Contacts
Contact: Seock-Ah Im, M.D., Ph.D. +82-2-2072-0850
Contact: Jee Hyun Kim, M.D., Ph.D. +82-31-713-5132

Locations
Korea, Republic of
Seoul National University Bundang Hospital Recruiting
Seongnam, Gyeonggi-Do, Korea, Republic of, 463-707
Contact: Yun Jin Kim    +82-31-787-1421      
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Eunkyung Kim    +82-2-2072-7616      
Sponsors and Collaborators
Hanmi Pharmaceutical Company Limited
Investigators
Principal Investigator: Seock-Ah Im, M.D., Ph.D. Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Hanmi Pharmaceutical Company Limited
ClinicalTrials.gov Identifier: NCT01764087     History of Changes
Other Study ID Numbers: HM-KXI-101, 2156
Study First Received: January 2, 2013
Last Updated: January 7, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Hanmi Pharmaceutical Company Limited:
Stomach Neoplasms
Breast Neoplasms
Carcinoma
Neoplasms
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Pharmacologic Actions

Additional relevant MeSH terms:
Neoplasms
Stomach Neoplasms
Breast Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Breast Diseases
Skin Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014