Safety Study of TAK-700 in Subjects With Prostate Cancer. - Full Text View

Sponsored by:	Takeda Global Research & Development Center, Inc.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00569153

Purpose

The purpose of this study is to determine the safety and tolerability of TAK-700 in patients with asymptomatic metastatic, androgen independent prostate cancer.

Condition	Intervention	Phase
Prostatic Neoplasms	Drug: TAK-700	Phase I Phase II

MedlinePlus related topics: Cancer Prostate Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	A Phase 1/2, Open-Label, Multiple-Dose Study of the Safety, Tolerability, and Pharmacokinetics of TAK-700 in Metastatic, Androgen-Independent Prostate Cancer Subjects

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Adverse events, vital signs, physical examination findings, concomitant medications and laboratory tests (hematology, serum chemistry, cardiac enzymes endocrine levels and urinalysis). [ Time Frame: Cycle 1: Weeks 1, 2, 3 and 4, then every 4 weeks thereafter. ] [ Designated as safety issue: No ]
Chest x-ray. [ Time Frame: Done at screening only - then, as clinically indicated. ] [ Designated as safety issue: No ]
Electrocardiogram. [ Time Frame: Cycle 1: Weeks: 1 and 2, then week 1 of each subsequent cycle. ] [ Designated as safety issue: No ]
Eastern Cooperative Oncology Group (ECOG) performance status. [ Time Frame: Cycle 1: Week 1, then week 1 of each subsequent cycle. ] [ Designated as safety issue: No ]
Calculated ejection fractions. [ Time Frame: Cycle 2: Week 1 and every subsequent cycle (once every 28 days). ] [ Designated as safety issue: No ]
Study compliance and monitoring. [ Time Frame: Weeks: 0, 1, 2, 3 and 4. After Cycle 1 ( the first 28 days) subjects are seen only once every 4 weeks (28 days) unless clinically indicated. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Endocrine levels (serum testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, luteinizing hormone and cortisol). [ Time Frame: Cycle 1: Weeks: 0, 1, 2, 3, 4 and week 1 of each subsequent Cycle. ] [ Designated as safety issue: No ]
Prostate-specific antigen response. [ Time Frame: Cycle 1: Weeks 1 and 3, then week 1 of each subsequent cycle. ] [ Designated as safety issue: No ]
Objective disease response by modified response evaluation criteria in solid tumors (RECIST) criteria and pharmacokinetic parameters. [ Time Frame: At Screening and every 12 weeks after study entry (after every 3 cycles of treatment). ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	October 2007
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: TAK-700 TAK-700 100 mg, 200 mg, 300 mg and 400 mg (dose escalation), tablets, orally, twice daily until disease progression or occurrence of an unacceptable adverse event.

Detailed Description:

Prostate cancer is the most common cancer diagnosed and the second most common cause of cancer death in men in North America. Current treatment strategies for hormone-sensitive prostate cancer includes targeting the reduction of circulating steroid hormones, or blocking their action in target tissues via androgen suppression either by surgical or medical castration (treatment with luteinizing hormone-releasing hormone). Unfortunately, surgical or medical forms of castration only remove the testicular source of androgen; they do not impact precursor molecules produced by the adrenal glands. These precursor molecules are subsequently metabolized to active androgens in the peripheral tissues, which then induce continued prostate tumor growth via androgen receptors. Subjects with locally advanced and metastatic disease have a poor prognosis. Hormonal therapy in the form of medical or surgical castration can induce significant long-term remissions. However, development of androgen-independent disease is inevitable and therapeutic options are limited. Prognosis is poor with a median survival of less than 12 months for symptomatic subjects.

An alternative therapeutic strategy for androgen deprivation is the use of antiandrogens. Antiandrogens, such as bicalutamide, flutamide, and nilutamide, inhibit the stimulatory effects of testosterone and dihydrotestosterone at the cellular androgen receptor level as competitive inhibitors. The most widely used antiandrogen, bicalutamide, has been compared with castration in clinical trials. In multicenter trials with long-term follow-up for survival, bicalutamide monotherapy was less effective than castration with respect to survival (a 6 week difference) in subjects with metastatic disease and not significantly different from castration with respect to either survival or time to progression in nonmetastatic, locally advanced prostate cancer. Side effects of bicalutamide and other antiandrogen treatments include hot flashes, breast pain, and gynecomastia.

Mitoxantrone in combination with prednisone has been shown to produce an improved palliative response rate and a longer duration of response but no improvement in overall survival compared with prednisone alone. Docetaxel a taxane, was approved for use in combination with prednisone for the treatment of metastatic androgen-independent prostate cancer in 2004 based on results of 2 randomized trials that reported a statistically significant median survival benefit of 2 to 3 months compared with mitoxantrone. High-dose ketoconazole, an antifungal agent, with 17m 20-lyase inhibition activity, has been used off-label in combination with hydrocortisone (to offset cortisol suppression as a side effect of ketoconazole), to reduce adrenally-derived androgens in androgen-independent prostate cancer, and is one treatment option for subjects with advanced prostate cancer progressing after androgen deprivation.

TAK-700, a nonsteroidal inhibitor of 17,20-lyase, is being developed as an endocrine therapy for relevant hormone-sensitive cancers like prostate cancer.

Subjects participating in this study will have been diagnosed with metastatic, androgen-independent prostate cancer for which second line therapy is indicated. Study visits will be scheduled at least weekly during initial treatment periods, and every 4 weeks thereafter until disease progression or an adverse event.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject has histologically- or cytologically-confirmed prostate adenocarcinoma with metastatic, progressive disease while on androgen deprivation therapy.
Subject has radiograph-documented (computed tomography, magnetic resonance imaging or x-ray) metastatic disease.
Subject has undergone orchiectomy or is expected to continue receiving luteinizing hormone-releasing hormone analogue therapy, and has a testosterone level of <50 ng/dL at screening.
Subject has discontinued all antiandrogen therapy (within 4 weeks for flutamide and within 6 weeks for all others) prior to their first dose of study drug.
Subject has a prostate-specific antigen level ≥5 ng/mL.
Subject has an Eastern Cooperative Oncology Group performance status of 0 to 2.
Subject has an absolute neutrophile count ≥1500/uL, a platelet count ≥100,000/uL and hemoglobin ≥10 g/dL.
Subject has a serum creatinine level <2.0 mg/dL.
Subject has serum aspartate aminotransferase levels ≤1.5 times the institutional upper limit of normal, and bilirubin levels ≤1.5 times the institutional upper limit of normal.
Subject has clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory, unless the results are deemed not clinically significant by the investigator or sponsor.
Subject has cardiac enzyme results (B-type natriuretic peptide, creatine kinase-MB, and troponins I and T) within the reference range for the testing laboratory.
Subject has normal or, in the opinion of the investigator, clinically insignificant, physical examination findings, electrocardiogram and chest x-ray results.
Subject has a screening ejection fraction that is above the lower limit of the institutional normal range.

Exclusion Criteria:

Subject has known hypersensitivity to TAK-700 or related compounds.
Subject has received prior therapy with aminoglutethimide or ketoconazole within 30 days prior to the first dose of study drug.
Subject has received prior chemotherapy for prostate cancer.
The subject has received any investigational compound within 30 days prior to first dose of study drug.
Subject has received prior herbal product known to decrease prostate-specific antigen levels (eg, Saw Palmetto, PC-SPES) within 30 days prior to the first dose of study drug.
Subject has received radiation therapy for prostate cancer within 30 days prior to first dose of study drug.
Subject uses corticosteroids (with the exception of inhaled steroids) concurrently or within 30 days prior to first dose of study drug.
Subject has current spinal cord compression, current bilateral hydronephrosis, or current bladder neck outlet obstruction.
Subject has any symptoms which the investigator deems related to prostate cancer, ie, bone pain, pelvic pain.
Subject has a history of another malignancy, other than basal cell carcinoma or stage I squamous cell carcinoma of the skin, within the last 5 years.
Subject has a history of adrenal insufficiency.
Subject has a history of myocardial infarction, ischaemic symptomatic heart disease, cardiac arrhythmias or thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 12 months prior to first dose of study drug.
Subject has uncontrolled hypertension defined as blood pressure of greater than 150 mmHg systolic and 90 mmHg diastolic at two separate measurements no more than 60 minutes apart during screening visit.
Subject has a history of congestive heart failure (New York Heart Association Class II or greater).
Subject is known to have human immunodeficiency virus infection, chronic hepatitis B or C or any other serious medical condition, disease or psychiatric illness at Screening that might affect life expectancy or make it difficult to successfully manage and follow the subject according to the protocol.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00569153

Contacts

Contact: Takeda Study Registration Call Center

800-778-2860

medicalinformation@tpna.com

Locations

United States, California
	Recruiting
Los Angeles, California, United States
United States, Illinois
	Recruiting
Chicago, Illinois, United States
United States, Ohio
	Recruiting
Cleveland, Ohio, United States

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

Medical Director

Takeda Global Research & Development Center

More Information

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	TAK-700_201, TAK-700-201
Study First Received:	December 4, 2007
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00569153
Health Authority:	United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

Androgen-independent prostate cancer, metastatic

Study placed in the following topic categories:

Prostatic Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on January 15, 2009