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TKI258 in Castrate Resistant Prostate Cancer
This study is not yet open for participant recruitment.
Verified by M.D. Anderson Cancer Center, July 2009
First Received: January 27, 2009   Last Updated: July 10, 2009   History of Changes
Sponsor: M.D. Anderson Cancer Center
Collaborator: Novartis
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00831792
  Purpose

Primary Objective:

  • To estimate overall survival and early response as characterized by a drop in prostate specific antigen (PSA).
  • To identify the PSA modulation in 40 selected patients with advanced prostate cancer and to correlate those findings with changes in bone remodeling markers.

Secondary Objectives:

  • To explore the potential association between serum PSA and bone turnover markers with bone marrow fibroblast growth factor receptor 1 (FGF R 1) and fibroblast growth factor 9 (FGF9) while on TKI 258.
  • To explore the predictive values of baseline FGF R 1, FGF9, and FGF signaling in serum and those in the bone marrow before and during treatment with TKI258.
  • To collect and archive bone marrow biopsies and aspirates, serum and plasma in study patients for later hypothesis generating associations.
  • To explore FGF R expression following eight weeks of TKI 258.

Condition Intervention Phase
Prostate Cancer
Drug: TK1258
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment
Official Title: An Observational Study of Continuous TKI258, in Castration-Resistant Prostate Cancer Patients Evaluating Markers of FGF Signaling in Bone Marrow Plasma.

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To study how changes in your blood PSA level might affect the rebuilding of healthy bones while you are being treated with TKI258 for prostate cancer. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2009
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
TK1258: Experimental Drug: TK1258
2 Capsules at 100 mg each by mouth twice daily (total of 400 mg per day), 28 day cycle.

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically proven adenocarcinoma of the prostate with tumor infiltration to the bone as seen on positive bone marrow biopsy and aspirate.
  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. Presence of metastatic bone disease
  7. Discontinue diethylstilbestrol (DES) or steroids treatment for >/= 4 weeks and for antiandrogens >/= 6 weeks
  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) Hemoglobin >/= 8.0 g/dL independent of transfusion; 3) Platelet count >/= 75,000/microL; 4) Serum albumin >/= 3.0 g/dL; 5) Serum creatinine < 1.5 x ULN or a calculated creatinine clearance > 60 mL/min (as calculated by Cockroft-Gault method) 6) 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 x ULN b) AST and ALT >/= 2.5 x ULN, (for patients with known liver metastasis, AST and ALT </= 5 x ULN is allowed)
  3. Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), Ketoconazole, finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (eg, Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug.
  4. Active infection or intercurrent illness that are not controlled
  5. Unstable angina, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, uncontrolled hypertension (blood pressure >140/90 mm Hg despite optimal medical therapy), New York Heart Association (NYHA) Class III or IV Congestive Heart Failure.
  6. Prior radiation therapy completed < 4 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug.
  7. 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.
  8. Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.
  9. Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study
  10. Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV)
  11. Acute or chronic hepatitis B or C
  12. Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 4-week washout period before treatment initiation
  13. 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.
  14. Long QT syndrome or bundle branch block or hemiblock or other history of life-threatening arrhythmia (unless the patient has been effectively treated for it and is considered stable). Participation in the study of patients with known nonpathologic right bundle branch block is at the discretion of the Principal Investigator.
  15. Known brain metastasis
  16. History of pituitary or adrenal dysfunction
  17. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
  18. Prior therapy with TKI258
  19. 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) grade of </= 1. Chemotherapy induced alopecia and grade 2 neuropathy is allowed.
  20. 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00831792

Contacts
Contact: Christopher Logothetis, MD 713-792-2830

Locations
United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Principal Investigator: Christopher Logothetis, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: U.T.M.D. Anderson Cancer Center ( Christopher Logothetis, MD/Professor )
Study ID Numbers: 2008-0510
Study First Received: January 27, 2009
Last Updated: July 10, 2009
ClinicalTrials.gov Identifier: NCT00831792     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Prostate Cancer
Advanced Prostate Cancer
Castrate Resistant Prostate Cancer
Prostate Specific Antigen
PSA
Castration-Resistant Prostate Cancer Patients
TK1258
CHIR-258

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Prostatic Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Neoplasms

ClinicalTrials.gov processed this record on November 20, 2009