Clinical trial NCT00390468 (phase 2, status: completed)
Conditions: metastatic cancer, pain, prostate cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2, N50.82, R07.2, R07.82, R10.13, R10.33, R14.1, R52, C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: tandutinib
SMILES: COC1=C(OCCCN2CCCCC2)C=C2N=CN=C(N3CCN(CC3)C(=O)NC3=CC=C(OC(C)C)C=C3)C2=C1
Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have histologically or cytologically confirmed adenocarcinoma of the
             prostate.

          2. Patients must have radiological evidence of bone metastases.

          3. Patients must have a castrate level of testosterone (</= 50ng/ml). For patients who
             are medically castrated, luteinizing hormone releasing hormone analog must continue to
             maintain testicular suppression.

          4. Patients must have evidence of progressive disease (e.g. progressive bone pain from
             bone metastases, increasing bidimensional disease on clinical examination or X-rays or
             appearance of new lesions on bone radiographs). Alternatively, for patients without
             such evidence of progression, PSA-progression is defined by 2 consecutive rises in
             prostate-specific antigen (PSA), each an absolute change of at least 1ng/ml, measured
             at least 2 weeks apart.

          5. A minimum PSA >/= 5ng/ml is required.

          6. Patients on anti-androgens should be discontinued from such therapy for at least 4
             weeks (for bicalutamide for at least 6 weeks), unless there is interim evidence of
             progression as defined in Inclusion #4.

          7. Patients must have had one prior taxane-based regimen but no prior known PDGFR,
             platelet-derived growth factor receptor, inhibitor (e.g. imatinib, SU11248,
             BAY43-9006) therapy is permitted.

          8. Age >/= 18 years. Because no dosing or adverse event data are currently available on
             the use of TANDUTINIB in patients < 18 years of age, children are excluded from this
             study.

          9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

         10. Patients must have adequate organ and marrow function as follows: leukocytes >/=
             3,000/mcL; absolute neutrophil count >/= 1,500/mcL; platelets >/= 100,000/mcL; total
             bilirubin within normal institutional limits; aspartate aminotransferase (AST or SGOT)
             and alanine aminotransferase (ALT or SGPT) </= 2.5 times institutional upper limit of
             normal; creatinine within normal institutional limits OR creatinine clearance >/= 40
             mL/min/1.73 m2 for patients with creatinine levels above institutional normal

         11. The effects of TANDUTINIB on the developing human fetus at the recommended therapeutic
             dose are unknown. For this reason and because receptor tyrosine kinase inhibitors are
             known to be teratogenic, men must agree to use adequate contraception (hormonal or
             barrier method of birth control, or abstinence) prior to study entry and for 3 months
             after completion of study therapy.

         12. Ability to understand and the willingness to sign a written informed consent document.

         13. Men of all races and ethnic groups are eligible for this trial. This is a study in
             prostate cancer and is therefore not applicable to women.

        Exclusion Criteria:

          1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from dose-limiting adverse events due to agents administered more than 4
             weeks earlier.

          2. Patients may not be receiving any other investigational agents or hormonal therapy
             besides that used to maintain medical castration. Glucocorticoid therapy for
             intercurrent medical illnesses such as asthma, Chronic Obstructive Pulmonary Disease
             (COPD) or rheumatoid arthritis flare will be allowed.

          3. Patients may not be co-medicated with an agent that causes QTc prolongation.

          4. Patients with a mean QTc >500msec (with Bazett's correction) in screening
             electrocardiogram or history of familial long QT syndrome are ineligible.

          5. Left ventricular ejection fraction (LVEF) <40%.

          6. Myocardial infarction within 6 months of enrollment or New York Heart Association
             (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.

          7. Ongoing vomiting, or nausea >/= Grade 2 (National Cancer Institute Common Terminology
             Criteria for Adverse Events (CTCAE) v3.0). If nausea, or vomiting is controlled with
             therapy (and therefore not Grade 2) such patients may be enrolled.

          8. Patients with any condition (e.g., gastrointestinal tract disease resulting in an
             inability to take oral medication or a requirement for IV alimentation, prior surgical
             procedures affecting absorption, or active peptic ulcer disease) that impairs their
             ability to swallow pills or absorb oral medications are excluded.

          9. History of chronic liver disease.

         10. Known or suspected primary muscular or neuromuscular disease (e.g., muscular
             dystrophy, myasthenia gravis).

         11. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to tandutinib. Patients who develop an acneiform/maculopustular rash while
             taking either gefitinib or erlotinib should not be prevented from receiving tandutinib
             unless the rash is considered an allergic reaction (angioedema/urticaria) or
             Stevens-Johnson syndrome.

         12. Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

         13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infections defined as requiring IV antibiotics on Day 1 of treatment or psychiatric
             illness/social situations that would limit compliance with study requirements.

         14. HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with TANDUTINIB. In addition, these
             patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated.