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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Xcovery Holding Company, LLC
Information provided by (Responsible Party):
Xcovery Holding Company, LLC Identifier:
First received: June 15, 2012
Last updated: February 2, 2016
Last verified: November 2015
This is the first human study to use X-396, 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 Intervention Phase
Advanced Solid Tumors
Non-small Cell Lung Cancer
Drug: X-396
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/2, First-in-Human, Dose-Escalation Study of X-396 in Patients With Advanced Solid Tumors and Expansion Phase in Patients With ALK-positive Non-Small Cell Lung Cancer

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: 100
Study Start Date: June 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (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 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.

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. Patients may have received prior crizotinib and/or second generation ALK TKIs.

    -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 drugs with a risk of causing prolonged QTc and/or Torsades de Pointes.
  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.
  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, California
City of Hope National Med Ctr Recruiting
Duarte, California, United States, 91010
Contact: Roy Maya    626-256-4673 ext 80115   
Principal Investigator: Karen Reckamp, M.D.         
UCSD Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Stephanie Hanan    858-822-6869   
Principal Investigator: Sandip Patel, M.D.         
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, Maryland
Walter Reed National Military Medical Center Recruiting
Bethesda, Maryland, United States, 20889
Contact: Virginia (Ginger) Schmidt    301-295-6814   
Principal Investigator: Corey Carter, M.D.         
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Bryan Marion    617-632-3383   
Principal Investigator: Leena Gandhi         
United States, Missouri
Washington University School of Medicine Recruiting
St. 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 Recruiting
Bronx, New York, United States, 10461
Contact: Danny Paucar    718-405-8539   
Principal Investigator: Haiying Cheng, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Catherine Schweitzer    614-685-5414   
Principal Investigator: Gregory Otterson, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Nicole Edwards    503-215-1833   
Principal Investigator: Rachel Sanborn, MD         
United States, Pennsylvania
Penn State Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Becky Miller    717-531-1003   
Principal Investigator: Chandra Belani, MD         
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Lindsay Hopkins    215-214-3789   
Principal Investigator: Renee Mehra         
United States, South Carolina
Medical University of South Carolina Not yet recruiting
Charleston, South Carolina, United States, 29425
Contact: Jason Dority    843-792-5853   
Principal Investigator: Carol Sherman, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37240
Contact: Rhonda Combs    800-811-8480   
Principal Investigator: Leora Horn, MD         
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Ainslie Rogers    615-524-4155   
Principal Investigator: Jeffrey Infante, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: George Blumenschein    855-873-4321      
Principal Investigator: George Blumenschein, MD         
United States, West Virginia
West Virginia University Hospital Recruiting
Morgantown, West Virginia, United States, 26506
Contact: Trish Beal    304-293-0609   
Principal Investigator: Patrick C Ma, MD, MSc         
United States, Wisconsin
University of Wisconsin Carbone Cancer Ctr Recruiting
Madison, Wisconsin, United States, 53792
Contact: Elise VolkmannVolkmann    608-262-8158   
Contact: Hilary R Hernan   
Principal Investigator: Ticiana Leal, M.D.         
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: February 2, 2016
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:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms processed this record on April 27, 2016