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

NCT01764087 | Unknown Phase 1

• 1 other identifier: HM-KXI-101
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific; Gastric Cancer; Breast Cancer

Keywords

Stomach Neoplasms; Breast Neoplasms; Carcinoma; Neoplasms; Paclitaxel; Tubulin Modulators; Antimitotic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Pharmacologic Actions

Outcome Measures

Primary Outcomes (2)

• Dose-limiting Toxicities (DLTs) in Phase I Portion

  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

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

• Tumor Overall Response Rates (ORRs) in Phase II Portion

  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

  In every 2 cycles up to end of the treatment, an expected average of 16 weeks

Secondary Outcomes (5)

• Pharmacokinetic (PK) Evaluation in Phase I Portion

  Time points at day 0, 1 and 8 in cycle 1

• The Preliminary Efficacy Data in Phase I Portion

  In every 2 cycles up to end of the treatment, an expected average of 8 weeks

• Safety in Phase II Portion

  From start of the treatment to end of the treatment, an expected average of 16 weeks

• The Efficacy Data in Phase II Portion

  Up to die, an expected average of 24 weeks

• Pharmacokinetic (PK) Evaluation in Phase II Portion

  Time points at day 1 and 8 in cycle 1

Other Outcomes (2)

• Pharmacodynamic (PD) Evaluation in Phase I Portion

  Time points at day 0 and 1 in cycle 1

• Exploratory Biomarker Evaluation in Phase II Portion

  Time points at day -6 and day 0

Study Arms (1)

KX2-391 and Paclitaxel

EXPERIMENTAL

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

Interventions

KX2-391 and Paclitaxel DRUG

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.

Also known as: KX01, Taxol

KX2-391 and Paclitaxel

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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)
• Aged ≥ 20 years
• ECOG (Eastern Cooperative Oncology Group) ≤ 2
• Life expectancy ≥ 12 weeks

You may not qualify if:

• Uncontrolled central nervous system metastasis
• Malignant ascites requiring surgical treatment
• Subjects who have blood malignancies including leukemia; or who have received or will receive bone marrow transplantation
• 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
• 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)
• Received other investigational product within 4 weeks prior to the administration of this study drug
• 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)
• History of hypersensitivity to paclitaxel, compounds with similar chemical structure, or cremophor (polyoxyethylated castor oil) ingredient
• Neuropathy of grade ≥ 3 based on clinical screening
• Known history of hepatitis B or C and known history of HIV serum positive

Sponsors & Collaborators

• Hanmi Pharmaceutical Company Limited: lead

Study Sites (2)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul, 110-744, South Korea

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Breast Neoplasms; Carcinoma; Neoplasms

Interventions

tirbanibulin; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Seock-Ah Im, M.D., Ph.D.

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

+82-2-2072-0850

Jee Hyun Kim, M.D., Ph.D.

CONTACT

+82-31-713-5132

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2013
• First Posted: January 9, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: May 1, 2016
• Last Updated: May 18, 2015

Record last verified: 2014-03

Locations

KR (2)