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Phase 1, First-in-Human, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of X-396 in Patients With Advanced Solid Tumors

Phase 1
18 Years
Open (Enrolling)
Advanced Solid Tumors

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Trial Information

Phase 1, First-in-Human, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of X-396 in Patients With Advanced Solid Tumors

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.

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

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

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

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

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 opinion, 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.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Description:

To evaluate the safety/tolerability of X-396 and determine the maximum tolerated dose (MTD) of X-396 as a single agent.

Outcome Time Frame:

12 months

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

June 2012

Completion Date:

December 2013

Related Keywords:

  • Advanced Solid Tumors
  • Cancer
  • Tumors
  • ALK
  • Advanced Malignancies
  • Carcinoma, Non-Small-Cell Lung
  • Inflammatory Myofibroblastic Tumors
  • Neoplasms



Vanderbilt UniversityNashville, Tennessee  37232-6305
Sarah Cannon Research InstituteNashville, Tennessee  37203