Tandutinib in Treating Patients With Progressive Prostate Cancer and Bone Metastases

NCT00390468 | Completed Phase 2 Results

• 5 other identifiers: NCI-2012-02865P30CA016672MDA-2005-0717NCI-7409CDR0000504104
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 8-week Freedom-From-Progression (FFP)

  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.

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

Study Arms (1)

Tandutinib (MLN518)

EXPERIMENTAL

500 mg twice daily, a small-molecule inhibitor of the type III receptor tyrosine kinases. Tandutinib (MLN518) previously known as CT53518.

Drug: Tandutinib

Interventions

Tandutinib DRUG

500 mg twice daily every day with doses taken approximately 12 hours apart, 28 day cycle.

Also known as: CT53518

Tandutinib (MLN518)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate.
• Patients must have radiological evidence of bone metastases.
• 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.
• 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.
• A minimum PSA \>/= 5ng/ml is required.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• 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
• 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.
• Ability to understand and the willingness to sign a written informed consent document.
• 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.

You may not qualify if:

• 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.
• 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.
• Patients may not be co-medicated with an agent that causes QTc prolongation.
• Patients with a mean QTc \>500msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome are ineligible.
• Left ventricular ejection fraction (LVEF) \<40%.
• 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.
• 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.
• 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.
• History of chronic liver disease.
• Known or suspected primary muscular or neuromuscular disease (e.g., muscular dystrophy, myasthenia gravis).
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Related Publications (1)

• 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.

  PMID: 21290244 RESULT

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Neoplasm Metastasis; Pain; Prostatic Neoplasms

Interventions

tandutinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

The study was closed to further accrual per design specifications.

Results Point of Contact

• Title: Quality Assurance Specialist
• Organization: UT MD Anderson Cancer Center

caperez@mdanderson.org

713-792-2830

Study Officials

• Paul Mathew, MD

  UT MD Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 18, 2006
• First Posted: October 19, 2006
• Study Start: October 1, 2006
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: May 28, 2014
• Results First Posted: June 7, 2011

Record last verified: 2013-01

Locations

US (1)