Safety Study of X-82 in Patients With Advanced Solid Tumors

This study is currently recruiting participants.
Verified August 2013 by Tyrogenex
Information provided by (Responsible Party):
Tyrogenex Identifier:
First received: February 14, 2011
Last updated: August 13, 2013
Last verified: August 2013

The purpose of this study is to determine the maximum tolerated dose (MTD) of X-82 as a single agent.

Condition Intervention Phase
Advanced Solid Tumors
Drug: X-82
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 I, First in Human, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of X-82 in Patients With Advanced Solid Tumors

Resource links provided by NLM:

Further study details as provided by Tyrogenex:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose (MTD) of X-82 as a single agent.

Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To characterize the preliminary pharmacokinetics (PK) of X-82 given as a single agent.

  • Preliminary biological activity [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To explore the preliminary biological activity and clinical tumor response after treatment with X-82 given as a single agent.

Estimated Enrollment: 60
Study Start Date: February 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: X-82 Drug: X-82
Dose escalation starting at 20 mg, oral once or twice a day, 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.


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

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy that is not responsive to standard therapies or for which there is no effective therapy.
  • Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Ability to swallow and retain oral medication.
  • Adequate organ system function, defined as follows:

    • Absolute neutrophil count (ANC) ≥1.5 x 109/L
    • Platelets ≥100 x 109/L
    • Hemoglobin ≥9 g/dL
    • Total bilirubin ≤1.5 times the upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x the upper limit of normal (ULN) if no liver involvement or ≤5 x the upper limit of normal with liver involvement.
    • Creatinine ≤ 1.5 x ULN, OR calculated creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault method, OR 24-hour measured urine creatinine clearance ≥ 50 mL/min.
  • Male patients willing to use adequate contraceptive measures.
  • 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 24 hours prior to initial trial treatment.
  • Patients must have measurable or evaluable disease.
  • Patients must be ≥ 18 years of age.
  • Patients entering this study must be willing to provide tissue from a previous tumor biopsy (if available) for correlative testing. If tissue is not available, a patient will still be eligible for enrollment into the study.
  • Willingness and ability to comply with trial and follow-up procedures.
  • Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

  • Patients currently receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy [with the exception of LHRH agonists for prostate cancer], surgery and/or tumor embolization).
  • Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of X-82. A minimum of 10 days between termination of the investigational drug and administration of X-82 is required. In addition, any drug-related toxicity should have recovered to grade 1 or less.
  • Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed ≥2 weeks). 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.
  • Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically related to X-82 (sunitinib, sorafenib or pazopanib) or to the active ingredient of X-82.
  • Concomitant use of drugs with a risk of causing prolonged QTc and/or Torsades de Pointes.
  • Concomitant use of herbal medications (i.e. 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.
  • Patients with known CNS metastases, unless metastases are treated and stable and the patients do not require systemic steroids
  • Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1mg allowed for port line patency permitted). Low molecular weight heparin (LMWH) will be allowed.
  • Females who are pregnant or breastfeeding.
  • Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of X-82.
  • Decreased left ventricular function at study entry defined as LVEF <50% by either Echocardiogram or MUGA scan.
  • Patients who have previously experienced myocardial infarction, severe/unstable angina, coronary/peripheral arterial bypass, symptomatic congestive heart failure (New York Heart Association [NYHA] Class 3 or 4), arterial thrombosis, cerebrovascular accident, or transient ischemia, in the 60 days prior to Day 1 of Cycle 1.
  • Patients with inadequately controlled hypertension (defined as BP > 150/100) with or without current antihypertensive medications. Patients with a history of additional risk factors for Torsades de Pointes (e.g. familial long QT syndrome, heart failure, left ventricular hypertrophy, slow heart rate (<45 bpm)).
  • Patient with a QTc interval ≥450 msecs. or other significant ECG abnormalities as determined the investigator.
  • 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.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol
  • Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol
  • Patients with a history of intolerance to, or significant toxicity with, VEGFR tyrosine kinase inhibitor(s) (TKI).
  • Patients entering the expansion after the determination of MTD are limited to previous treatment with one anti-VEGFR TKI
  Contacts and Locations
Please refer to this study by its identifier: NCT01296581

Contact: Gina Courtney, M.D. 615-339-4214

United States, Oklahoma
Peggy and Charles Stephens Oklahoma Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Rachel Higbee    405-271-8777   
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: Tyrogenex Identifier: NCT01296581     History of Changes
Other Study ID Numbers: X82-CLI-101
Study First Received: February 14, 2011
Last Updated: August 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Tyrogenex:

Additional relevant MeSH terms:
Neoplasms processed this record on April 21, 2014