Clinical trial NCT00390468: Tandutinib in Treating Patients With Progressive Prostate Cancer and Bone Metastases
Official title: A Phase II Study of Tandutinib (MLN518) in Androgen-Independent Prostate Cancer With Bone Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Cancer
Pain
Prostate Cancer
Keywords: Tandutinib
MLN518
CT53518
pain
adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer
bone metastases
hormone-based castration
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-10-19
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Tandutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well tandutinib works in treating patients with progressive prostate cancer and bone metastases.

Detailed description: OBJECTIVES:

Primary

* Determine the time to progression in patients with progressive androgen-independent prostate cancer with bone metastases treated with tandutinib.

Secondary

* Determine the prostate-specific antigen (PSA) decline rate by 50% (PSA response), using the PSA Working Group Criteria, in patients treated with this regimen .
* Evaluate modulation of bone pain and bone markers in patients treated with this regimen.
* Determine the objective tumor response by RECIST (Response Evaluation Criteria In Solid Tumors) criteria in patients treated with this regimen.
* Determine the qualitative and quantitative toxicity of this regimen in these patients.

OUTLINE: Patients receive oral tandutinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Bone pain is assessed at baseline, on day 1 of course 3, and at disease progression.

After completion of study treatment, patients are followed for 4 weeks.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

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.

Primary outcomes:
measure: 8-week Freedom-From-Progression (FFP)
timeFrame: 8 weeks; repeat assessments performed every 8 weeks after criteria for response first met.
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: UT MD Anderson Cancer Center
name: Paul Mathew, MD
role: STUDY_CHAIR
References:
citation: Mathew P, Tannir N, Tu SM, Wen S, Guo CC, Marcott V, Bekele BN, Pagliaro L. Accelerated disease progression in prostate cancer and bone metastases with platelet-derived growth factor receptor inhibition: observations with tandutinib. Cancer Chemother Pharmacol. 2011 Oct;68(4):889-96. doi: 10.1007/s00280-011-1567-2. Epub 2011 Feb 3.