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An Observational Study of Continuous TKI258, in Castration-Resistant Prostate Cancer Patients Evaluating Markers of FGF Signaling in Bone Marrow Plasma.


Phase 2
N/A
N/A
Open (Enrolling)
Male
Prostate Cancer

Thank you

Trial Information

An Observational Study of Continuous TKI258, in Castration-Resistant Prostate Cancer Patients Evaluating Markers of FGF Signaling in Bone Marrow Plasma.


The Study Drug:

TKI258 is designed to perform several anti-tumor functions, including cutting off the blood
supply to tumors. Researchers think this may help slow or stop the growth of prostate
cancer.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 4 capsules of
TKI258 1 time each day for 5 days in a row followed by 2 days of rest (Days 1-5, 8-12,
15-19, and 22-26 of each 28-day study "cycle"). You should take the TKI258 capsules with
about 8 ounces of water and at least 1 hour before a meal (breakfast) or at least 2 hours
following a meal (breakfast). If you want, you may take the drug with a meal that has fewer
than 500 calories and 20 grams of fat.

Study Visits:

Every 28 days makes up 1 study "cycle."

On Day 1 of Cycle 1 and all cycles after that, the following tests and procedures will be
performed:

- Your complete medical history will be recorded.

- You will be asked about any drugs or treatments you may be receiving.

- You will be asked about any side effects you may have experienced.

- You will have a physical exam, including measurement of your vital signs and weight.

- Your performance status will be evaluated.

- Blood (about 2 tablespoons) will be collected for routine tests. This blood will also
be tested to measure your PSA.

- You will have a triplicate ECG (3 ECGs in a row) before you take the study drug. You
will also have 1 ECG about 6 hours after you take the study drug.

On Day 12 (+/- 3 days) of Cycles 1 and 2, and day 26 of Cycle 1 (+/- 3 days) blood (about 1
tablespoon) will be collected for routine tests. Part of the Cycle 2 blood draw will be
used to measure the amount of TKI258 in your system. Note that the Day 26 of Cycle 1 visit
could end up being scheduled on the same day as the Day 1 of Cycle 2 visit described above.

On Day 1 of Cycle 2 and every odd numbered Cycle after this (Cycles 3, 5, 7and so on), the
following tests and procedures will be performed:

- Blood (about 2 teaspoons) will be collected for routine tests.

- Urine will be collected to test for markers relating to your bone.

At the end of every cycle (about Day 26), you will have an ECG.

Every 3 Cycles (about every 12 weeks), the following tests and procedures will be performed:

- Blood (about 1 teaspoon) will be drawn to measure your levels of heart enzymes

- You will have an echocardiogram or MUGA scan like the one you had at the screening
visit to check your heart function.

About 7-10 weeks after your first dose of study drug, you will have another bone marrow
biopsy and aspiration performed to check the status of the disease and for biomarker
testing.

CT and/or bone scans will be performed every 8 weeks for the first 6 months and every 3
months after that to check the status of the disease.

Length of Study:

You may remain on study for as long as you are benefiting. You will be taken off study if
intolerable side effects occur or if the disease gets worse.

End-of-Study Visit:

Within 4 weeks after your last dose of the study drug, you will return to the clinic for an
end-of-study visit. The following tests and procedures will be performed:

- You will have a physical exam, including measurement of your vital signs, and weight.

- Your performance status will be evaluated.

- You will be asked about any drugs or treatments you may be receiving.

- You will be asked about any side effects you have experienced since you last visit.

- Blood (about 3 tablespoons) and urine will be collected for routine tests. This blood
will also be tested to measure certain hormones, heart enzymes, and PSA.

- You will have a chest x-ray, bone scan, and either a computed tomography (CT) or
magnetic resonance imaging (MRI) scan of your abdomen and pelvis to check the status of
the disease.

- You will have an ECG and either an echocardiogram or a MUGA scan.

- You will have a bone marrow biopsy and aspiration performed to check the status of the
disease and for biomarker testing.

Long-Term Follow-up:

Once you are no longer on this study, the research staff will check up on you about every 3
months. This update will consist of a phone call, an e-mail, or a review of your medical
and/or other records. You will not have any extra tests, procedures, or study visits. If
contacted by phone, the call would only last about 5 minutes.

This is an investigational study. TKI258 is not FDA approved or commercially available. It
is being used in this study for research purposes only.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.


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 Performance Status >/= 50%)

3. Serum testosterone levels
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)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 Cockroft-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.) 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 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).

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Patient Overall Survival Time + Early Response Time as characterized by a drop in PSA

Outcome Time Frame:

Continously from baseline until disease progression

Safety Issue:

No

Principal Investigator

Paul Corn, MD, PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2008-0510

NCT ID:

NCT00831792

Start Date:

April 2010

Completion Date:

Related Keywords:

  • Prostate Cancer
  • Prostate Cancer
  • Advanced Prostate Cancer
  • Castrate Resistant Prostate Cancer
  • Prostate Specific Antigen
  • PSA
  • Castration-Resistant Prostate Cancer Patients
  • TK1258
  • CHIR-258
  • Prostatic Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030