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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01625234
Recruitment Status : Recruiting
First Posted : June 21, 2012
Last Update Posted : March 7, 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 170 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 : 190 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 2020
Estimated Study Completion Date : November 2021

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 be ALK TKI-naive or may have received prior crizotinib and/or second generation ALK TKIs. In addition, patients with a known ALK 1198 mutation will be allowed.

    -For the expanded cohort portion of the study, patients must have NSCLC with ALK genomic alterations; however, patients will be allowed to enroll based on local FDA-approved ALK 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. Willingness and ability to comply with the trial and follow-up procedures.
  11. 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. A minimum of 10 days between treatment and X-396 and 2 days between ALK TKI and X-396.
  3. Any major surgery, radiotherapy, or immunotherapy within the last 21 days (focal radiation does not require a washout period; ≥4 weeks for WBRT). 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. Patients receiving CYP3A substrates with narrow therapeutic indices, strong CYP3A inhibitors, and strong CYP3A inducers.
  8. Concomitant use of herbal medications at least 7 days prior to the first dose of study drug and throughout participation in the trial.
  9. Females who are pregnant or breastfeeding.
  10. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of X-396.
  11. Clinically significant cardiovascular disease.
  12. 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.
  13. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  14. 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.
  15. 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 identifier (NCT number): NCT01625234

  Hide Study Locations
United States, California
City of Hope National Med Ctr Recruiting
Duarte, California, United States, 91010
Contact: Michael Donor    626-256-4673 ext 80749   
Principal Investigator: Karen Reckamp, M.D.         
UCSD Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Klarissa Son    858-822-5369   
Principal Investigator: Sandip Patel, M.D.         
Loma Linda University Cancer Center Withdrawn
Loma Linda, California, United States, 92354
University of Southern California Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Gina Tse    323-865-3962   
Principal Investigator: Barbara Gitlitz, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Richard Quick    650-723-2983   
Principal Investigator: Heather Wakelee, M.D.         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Heloise Borges    813-745-6141   
Principal Investigator: Alberto Chiappori, MD         
United States, Maryland
Walter Reed National Military Medical Center Recruiting
Bethesda, Maryland, United States, 20889
Contact: Virginia (Ginger) Schmidt    301-295-6814   
Principal Investigator: Christina Brzezniak, M.D.         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Bryan Marion    617-632-3383   
Principal Investigator: Geoffrey Oxnard         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Melissa Meredith, MS, CCRP    314-362-4140   
Contact: Ian McGowan    314-747-7569   
Principal Investigator: Saiama N Waqar, MD         
United States, New York
Montefiore Medical Center Withdrawn
Bronx, New York, United States, 10461
New York University Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact: Taylor Mazac    929-455-2435   
Principal Investigator: Leena Gandhi         
Stony Brook University Cancer Center Withdrawn
Stony Brook, New York, United States, 11794
United States, Ohio
Ohio State University Withdrawn
Columbus, Ohio, United States, 43210
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Brenda Fisher    503-215-2613   
Principal Investigator: Rachel Sanborn, MD         
United States, Pennsylvania
Penn State Hershey Medical Center Withdrawn
Hershey, Pennsylvania, United States, 17033
Fox Chase Cancer Center Withdrawn
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Medical University of South Carolina Withdrawn
Charleston, South Carolina, United States, 29425
United States, Tennessee
Sarah Cannon Research Institute Completed
Nashville, Tennessee, United States, 37203
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37240
Contact: Rhonda Combs    800-811-8480   
Principal Investigator: Leora Horn, MD         
United States, Texas
MD Anderson Cancer Center Withdrawn
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia Cancer Center Withdrawn
Charlottesville, Virginia, United States, 22903
United States, West Virginia
West Virginia University Hospital Withdrawn
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
University of Wisconsin Carbone Cancer Ctr Recruiting
Madison, Wisconsin, United States, 53792
Contact: Tessa Kroeninger    608-262-5706   
Contact: Hilary R Hernan   
Principal Investigator: Ticiana Leal, M.D.         
Sponsors and Collaborators
Xcovery Holding Company, LLC

Responsible Party: Xcovery Holding Company, LLC Identifier: NCT01625234     History of Changes
Other Study ID Numbers: X396-CLI-101
First Posted: June 21, 2012    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: March 2018

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