Phase 1 Safety Study of X-396, an Oral ALK Inhibitor, in Patients With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Xcovery Holding Company, LLC
Information provided by (Responsible Party):
Xcovery Holding Company, LLC Identifier:
First received: June 15, 2012
Last updated: August 13, 2013
Last verified: August 2013

This is the first human study to use X-396, a drug being developed for treatment of advanced cancers. The main purpose of the study is to determine the largest amount of X-396 that can be safely given to humans (the maximum tolerated dose). The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the efficacy of X-396.

Condition Intervention Phase
Advanced Solid Tumors
Drug: X-396
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1, First-in-Human, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of X-396 in Patients With Advanced Solid Tumors

Resource links provided by NLM:

Further study details as provided by Xcovery Holding Company, LLC:

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

Secondary Outcome Measures:
  • Plasma Concentrations (Cmax, Tmax, AUC, half-life) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To characterize the preliminary pharmacokinetics including Cmax, Tmax, AUC, half-life of X-396 given as a single agent

  • Preliminary Tumor Response [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To explore the preliminary clinical tumor response after treatment with X-396 given as a single agent.

Estimated Enrollment: 60
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: X-396
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
Oral, ALK inhibitor

Detailed Description:

This is the first study of X-396 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 25 additional patients will also be given X-396 to further determine the activity of X-396 in patients with and without certain tumor biomarkers.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy that is not responsive to at least 1 prior standard regimen for advanced disease or for which there is no approved therapy or for patients that refuse standard therapy. As long as the therapy was tolerated, patients in the dose escalation portion may have received prior crizotinib and/or second generation ALK TKIs, while patients in the expanded cohort portion may have received prior crizotinib.
  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 CNS metastases are eligible.
  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 and who have a negative serum or urine pregnancy test within 1 week prior to initial trial treatment.
  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.
  10. Patients entering this study will be asked to provide tissue for correlative testing.
  11. For the expanded cohort portion of the study, patients in the cohort with ALK genomic alterations must be ALK-positive by FISH. Patients in the ALK- negative, MET-negative cohort must be negative for ALK by FISH and MET alterations by immunohistochemistry(IHC).
  12. Willingness and ability to comply with the trial and follow-up procedures.
  13. 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 (limited palliative radiation is allowed ≥2 weeks prior to the first dose; ≥4 weeks for whole brain radiotherapy). Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C). 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 drugs with a risk of causing prolonged QTc and/or Torsades de Pointes.
  8. Concomitant use of herbal medications (e.g., St. John's wort, Kava, ephedra [ma huang], ginko biloba) 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, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  13. Patients that, in the investigator's judgment, have tolerated poorly prior treatment with an ALK or MET inhibitor.
  14. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  15. 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.
  16. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
  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 identifier: NCT01625234

United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Julie Pfrommer    615-524-4110   
Principal Investigator: Jeffrey Infante, MD         
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37240
Contact: Barbara Cardin    800-811-8480   
Principal Investigator: Leora Horn, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Justina Price    713-794-5325   
Principal Investigator: George Blumenschein, MD         
Sponsors and Collaborators
Xcovery Holding Company, LLC
  More Information

Responsible Party: Xcovery Holding Company, LLC Identifier: NCT01625234     History of Changes
Other Study ID Numbers: X396-CLI-101
Study First Received: June 15, 2012
Last Updated: August 13, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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

Additional relevant MeSH terms:
Neoplasms processed this record on August 20, 2014