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A Phase II Study of Tandutinib (MLN518) in Androgen-Independent Prostate Cancer With Bone Metastases

Phase 2
18 Years
Not Enrolling
Metastatic Cancer, Pain, Prostate Cancer

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Trial Information

A Phase II Study of Tandutinib (MLN518) in Androgen-Independent Prostate Cancer With Bone Metastases



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


- 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

- 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.

Inclusion Criteria:

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

2. Patients must have radiological evidence of bone metastases.

3. Patients must have a castrate level of testosterone ( 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

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) 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

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

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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

8-week Freedom-From-Progression (FFP)

Outcome Description:

Simon 2 stage design for freedom from progression at 8 weeks where time-to-progression defined as time of initiation of therapy to first determination of progression of disease by clinical, radiological or serological criteria: Frequency of p-PDGFR (phosphorylated platelet-derived growth factor receptor) expression in bone marrow biopsy specimens, prostate-specific antigen (PSA) declines by 50% sustained for 4 weeks, measurable disease outcomes by RECIST (Response Evaluation Criteria In Solid Tumors) criteria, and quantitative/qualitative toxicities assessed.

Outcome Time Frame:

8 weeks; repeat assessments performed every 8 weeks after criteria for response first met.

Safety Issue:


Principal Investigator

Paul Mathew, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2006

Completion Date:

November 2009

Related Keywords:

  • Metastatic Cancer
  • Pain
  • Prostate Cancer
  • Tandutinib
  • MLN518
  • CT53518
  • pain
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage IV prostate cancer
  • bone metastases
  • hormone-based castration
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Prostatic Neoplasms
  • Bone Neoplasms
  • Bone Marrow Diseases



M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009