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TKI258 in Castrate Resistant Prostate 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. Read our disclaimer for details. Identifier: NCT00831792
Recruitment Status : Completed
First Posted : January 29, 2009
Results First Posted : September 11, 2019
Last Update Posted : September 11, 2019
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to learn if a decrease in the levels of prostate specific antigen (PSA) may be linked with the status of prostate cancer that has spread to the bones. Researchers also want to learn how changes in your blood PSA level might affect the rebuilding of healthy bones while you are being treated with TKI258 for prostate cancer.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: TK1258 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Observational Study of Continuous TKI258, in Castration-Resistant Prostate Cancer Patients Evaluating Markers of FGF Signaling in Bone Marrow Plasma
Actual Study Start Date : April 7, 2010
Actual Primary Completion Date : June 12, 2017
Actual Study Completion Date : June 12, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: TK1258
4 capsules (100 mg/capsules) of TKI 258 by mouth once daily (total of 400 mg of TKI258 per day). Following an initial 4-week cycle at a starting dose of 400 mg 5 days- on and 2 days off, TKI258 may be escalated to 500 mg/day 5 days-on/2 days off if no significant Grade3/4 AEs or laboratory abnormalities are observed.
Drug: TK1258
4 capsules (100 mg/capsules) of TKI 258 by mouth once daily (total of 400 mg of TKI258 per day).
Other Name: CHIR-258

Primary Outcome Measures :
  1. The Number of Participants With Improvement, Disease Progression or Stable Disease [ Time Frame: From the time of enrollment until 30 days beyond the date of the last study drug administration ]
    Three consecutive PSA elevations above nadir or baseline are required for progression. Each increment in PSA should be a minimum of 1 ng/ml and at least 2 weeks apart or will not count. The time of PSA progression will be taken as the time of the first of these PSA elevations that represents an increment by at least 25% above the nadir or baseline. Given that increments in PSA do not always represent treatment failure, particularly when novel agents with uncertain effects on PSA levels are being evaluated, clinical and radiological correlation is recommended at the discretion of the treating physician. In patients with PSA progression alone without clinical or radiological evidence of disease progression, continued therapy on study is at the discretion of the treating physician in consultation with the principal investigator.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.
  2. Eastern Cooperative Oncology Group (ECOG) performance status </= 2. (Karnofsky Performance Status >/= 50%)
  3. Serum testosterone levels </= 50ng/ml
  4. Ongoing gonadal androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy. Patients, who have not had an orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at appropriate frequency for the duration of the study.
  5. Progression of disease despite androgen ablation (either documented osseous or soft tissue metastatic disease progression or by PSA criteria progression). a)Definition of Progressive disease by PSA evidence: a PSA level of at least 5 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. The participant will need a baseline test and a test to show that the PSA has increased.
  6. Discontinue diethylstilbestrol (DES) for >/= 4 weeks and antiandrogens >/= 6 weeks prior to study drug.
  7. Discontinue any steroids prescribed to specifically treat prostate cancer (for e.g as a secondary hormonal manipulation or for cord compression) >/= 4 weeks prior to study drug. Steroids chronically prescribed for a non-cancer-related illness (e.g. asthma or COPD) that is well controlled with medical management are permissible to an equivalent of < 10 mg Prednisone daily.
  8. Antiandrogen Withdrawal: Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen. Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression.
  9. For patients receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation.
  10. For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation
  11. Laboratory Requirements: 1) Adequate adrenal function (absence of symptoms or electrolyte imbalances that indicate adrenal insufficiency); 2) White blood cell count (WBC) count >/= 3,000/microl; 3) Absolute Neutrophil Count (ANC) >/= 1,500/microl; 4) Hemoglobin >/= 8.0 g/dL independent of transfusion; 5) Platelet count >/= 75,000/microL; 6) Serum albumin >/= 3.0 g/dL; 7) Serum creatinine < 1.5 x ULN or a calculated creatinine clearance > 60 mL/min (as calculated by Cockcroft-Gault method) 8) Serum potassium >/= 3.5 mmol/L
  12. No evidence of chronic or acute DIC (Disseminated Intravascular Coagulation) or bleeding tendency and no angina at rest.
  13. Patient must be willing and able to comply with protocol requirements. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must also have signed an authorization for the release of their protected health information.

Exclusion Criteria:

  1. Histologic variants other than adenocarcinoma in the primary tumor
  2. Abnormal liver functions consisting of any of the following: a) Serum bilirubin >/= 1.5 * upper limit of normal (ULN) b) AST and ALT > 2.5 * ULN
  3. Therapy with other hormonal therapy, including any dose of Ketoconazole, finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (eg, Saw Palmetto and PC-SPES) within 4 weeks of study drug.
  4. Requirement for corticosteroids greater than the equivalent of 7.5 mg of prednisone daily.
  5. Therapy with samarium or strontium within 8 weeks prior to first dose of study drug.
  6. Active infection or concomitant illness that is not controlled with medical management.
  7. Prior radiation therapy completed < 4 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug.
  8. Any currently active second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a currently active malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next 3 months.
  9. Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.
  10. Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study
  11. Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV)
  12. Acute or chronic hepatitis B or C
  13. Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 4-week washout period before treatment initiation
  14. Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug. Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy during the study.
  15. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a.) History or presence of serious uncontrolled ventricular arrhythmias or presence of atrial fibrillation; b.) Clinically significant resting bradycardia (< 50 beats per minute); c.) Left ventricular ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is higher);
  16. (# 13 Conti'd) Any of the following within 6 months prior to study entry: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE); e.) Uncontrolled hypertension defined by an SBP>150 and/or a DBP>100 mm Hg with or without anti-hypertensive medication; f.) Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring 2 or more interventions per month.
  17. History of pituitary or adrenal dysfunction
  18. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
  19. Prior therapy with TKI258
  20. Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 3.0) grade of </= 1. Chemotherapy induced alopecia and grade 2 neuropathy is allowed.
  21. Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study.
  22. Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 8 weeks after the end of study treatment. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of child-bearing potential is defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months).

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): NCT00831792

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
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Principal Investigator: Paul Corn, MD, PHD M.D. Anderson Cancer Center
  Study Documents (Full-Text)

Documents provided by M.D. Anderson Cancer Center:

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00831792    
Other Study ID Numbers: 2008-0510
NCI-2011-01106 ( Registry Identifier: NCI CTRP )
First Posted: January 29, 2009    Key Record Dates
Results First Posted: September 11, 2019
Last Update Posted: September 11, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Prostate Cancer
Advanced Prostate Cancer
Castrate Resistant Prostate Cancer
Prostate Specific Antigen
Castration-Resistant Prostate Cancer Patients
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases