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Phase 1/2 Study of X-396, an Oral ALK Inhibitor, in Patients With ALK-positive Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01625234
Recruitment Status : Recruiting
First Posted : June 21, 2012
Last Update Posted : January 3, 2018
Information provided by (Responsible Party):
Xcovery Holding Company, LLC

Brief Summary:
This is the first human study to use X-396 (ensartinib), a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the largest amount of X-396 that can be safely given to humans (the maximum tolerated dose). Once the recommended Phase 2 dose has been determined, an expansion phase will assess the preliminary anti-tumor activity of X-396 in ALK-positive non-small cell lung cancer. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the efficacy of X-396.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Non-small Cell Lung Cancer Drug: X-396 (ensartinib) Phase 1 Phase 2

Detailed Description:
This is the first study of X-396 (ensartinib) in humans and the investigational drug will be given as a once or twice daily oral dose in 28 day cycles until there is disease progression or unacceptable safety issues. X-396 will be given to small groups of patients (1 - 6) at each dose level and the patients will be observed to see if there are any adverse safety effects. As long as there are no unacceptable safety issues after 28 days, the dose of X-396 will be increased for the next group of patients. This process will continue until the maximum tolerated dose (MTD) of X-396 is reached. Once the MTD is reached, up to 60 additional patients will also be given X-396 to further determine the activity of X-396 in patients with ALK-positive non-small cell lung cancer. These additional patients will be enrolled in the following 5 expansion cohorts: ALK TKI-naïve patients, patients that progressed on crizotinib, patients that progressed on one or more 2nd generation ALK TKIs (patients may or may not have also received prior crizotinib), patients with asymptomatic CNS metastases, and patients with leptomeningeal disease.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2, First-in-Human, Dose-Escalation Study of X-396 (Ensartinib) in Patients With Advanced Solid Tumors and Expansion Phase in Patients With ALK-positive Non-Small Cell Lung Cancer
Study Start Date : June 2012
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: X-396 (ensartinib)
Dose escalation starting at 25 mg, oral once or twice a day, 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops
Drug: X-396 (ensartinib)
Oral, ALK inhibitor

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 12 months ]
    To evaluate the safety/tolerability of X-396 (ensartinib) and determine the maximum tolerated dose (MTD) of X-396 as a single agent.

Secondary Outcome Measures :
  1. Plasma Concentrations (Cmax, Tmax, AUC, half-life) [ Time Frame: 18 months ]
    To characterize the preliminary pharmacokinetics including Cmax, Tmax, AUC, half-life of X-396 given as a single agent

  2. Preliminary Tumor Response [ Time Frame: 18 months ]
    To explore the preliminary clinical tumor response after treatment with X-396 (ensartinib) given as a single agent.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy. Patients may have received prior crizotinib and/or second generation ALK TKIs (patient must have progressed on alectinib).

    -For the expanded cohort portion of the study, patients must have NSCLC with ALK genomic alterations positive by FISH or IHC testing done centrally; however, patients will be allowed to enroll based on local ALK FISH or IHC results.

  2. Eastern Cooperative Group ECOG) Performance Status score of 0 or 1.
  3. Ability to swallow and retain oral medication.
  4. Adequate organ system function.
  5. Patients with treated or untreated asymptomatic CNS metastases may be allowed to enroll.
  6. Male patients willing to use adequate contraceptive measures.
  7. Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures.
  8. Patients must be ≥ 18 years of age.
  9. Patients must have measurable or evaluable disease for the dose escalation portion of the study and measurable disease for the expanded cohort portion of the study (except for patients in the CNS metastases and leptomeningeal cohorts).
  10. Patients entering this study will be asked to provide tissue for correlative testing (if available).
  11. Willingness and ability to comply with the trial and follow-up procedures.
  12. Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

  1. Patients currently receiving cancer therapy.
  2. Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of X-396.
  3. Any major surgery, radiotherapy, or immunotherapy within the last 21 days. Chemotherapy regimens with delayed toxicity within the last 4 weeks. Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks.
  4. Prior stem cell transplant.
  5. Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically related to X-396 (e.g., crizotinib) or to the active ingredient of X-396.
  6. Patients with primary CNS tumors are ineligible.
  7. Concomitant use of herbal medications at least 7 days prior to the first dose of study drug and throughout participation in the trial.
  8. Females who are pregnant or breastfeeding.
  9. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of X-396.
  10. Clinically significant cardiovascular disease.
  11. Patients who are immunosuppressed (including known HIV infection), have a serious active infection at the time of treatment, have known hepatitis C, or have any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  12. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  13. Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol or would impart excessive risk associated with study participation that would make it inappropriate for the patient to be enrolled.
  14. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01625234

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Sponsors and Collaborators
Xcovery Holding Company, LLC

Responsible Party: Xcovery Holding Company, LLC
ClinicalTrials.gov Identifier: NCT01625234     History of Changes
Other Study ID Numbers: X396-CLI-101
First Posted: June 21, 2012    Key Record Dates
Last Update Posted: January 3, 2018
Last Verified: December 2017

Keywords provided by Xcovery Holding Company, LLC:
Advanced Malignancies
Carcinoma, Non-Small-Cell Lung
Inflammatory Myofibroblastic Tumors

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms