TKI258 in Castrate Resistant Prostate Cancer

NCT00831792 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2008-0510NCI-2011-01106
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Advanced Prostate Cancer; Castrate Resistant Prostate Cancer; Prostate Specific Antigen; PSA; Castration-Resistant Prostate Cancer Patients; TK1258; CHIR-258

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With Improvement, Disease Progression or Stable Disease

  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.

  From the time of enrollment until 30 days beyond the date of the last study drug administration

Study Arms (1)

TK1258

EXPERIMENTAL

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

Interventions

TK1258 DRUG

4 capsules (100 mg/capsules) of TKI 258 by mouth once daily (total of 400 mg of TKI258 per day).

Also known as: CHIR-258

TK1258

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 2. (Karnofsky Performance Status \>/= 50%)
• Serum testosterone levels \</= 50ng/ml
• 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.
• 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.
• Discontinue diethylstilbestrol (DES) for \>/= 4 weeks and antiandrogens \>/= 6 weeks prior to study drug.
• 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.
• 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.
• For patients receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation.
• For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation
• 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
• No evidence of chronic or acute DIC (Disseminated Intravascular Coagulation) or bleeding tendency and no angina at rest.
• 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.

You may not qualify if:

• Histologic variants other than adenocarcinoma in the primary tumor
• 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
• 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.
• Requirement for corticosteroids greater than the equivalent of 7.5 mg of prednisone daily.
• Therapy with samarium or strontium within 8 weeks prior to first dose of study drug.
• Active infection or concomitant illness that is not controlled with medical management.
• Prior radiation therapy completed \< 4 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug.
• 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.
• Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.
• Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study
• Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV)
• Acute or chronic hepatitis B or C
• Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 4-week washout period before treatment initiation
• 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.
• 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);

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Corn,Paul,M.D. Ph.D. / Genitourinary Medical Oncology
• Organization: UT MD Anderson Cancer Center

PCORN@MDANDERSON.ORG

713-792-7734

Study Officials

• Paul Corn, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2009
• First Posted: January 29, 2009
• Study Start: April 7, 2010
• Primary Completion: June 12, 2017
• Study Completion: June 12, 2017
• Last Updated: September 11, 2019
• Results First Posted: September 11, 2019

Record last verified: 2019-08

Locations

US (1)