Exogenous Testosterone Plus Dutasteride for the Treatment of Castrate Metastatic Prostate Cancer - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborators:	GlaxoSmithKline University of Washington
Information provided by (Responsible Party):	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00853697

Purpose

Usually, the male hormone testosterone makes prostate cancer cells grow. Lowering testosterone usually stops the growth of prostate cancer. However, after a period of time without testosterone, prostate cancer cells learn to grow again.

You are able to join this trial because your prostate cancer is growing even though you have very low levels of testosterone. Studies have shown that high doses of testosterone, in this situation, can cause prostate cancer cells to stop growing.

The investigators did a study several years ago in which the investigators gave high doses of testosterone to patients such as yourself. The investigators showed that giving testosterone in this situation was safe. The investigators also showed that the investigators could, in some cases, make the PSA go down using high-dose testosterone.

The investigators believe that they can improve this type of treatment by combining testosterone with another drug called dutasteride. Dutasteride is another type of hormone. It should make testosterone levels rise. The investigators believe that combination of dutasteride and testosterone will be more a more powerful regimen against your cancer than testosterone alone.

Condition	Intervention	Phase
Prostate Cancer Castration-resistant, Metastatic	Other: testosterone (AndroGel®) with the 5α-reductase inhibitor dutasteride	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Trial of Exogenous Testosterone Plus Dutasteride for the Treatment of Castrate Metastatic Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Dutasteride Oxymesterone Testosterone enanthate Testosterone undecanoate

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

determine anti-tumor effects of the combination of testosterone + dutasteride in pts with castration-resistant prostate ca, as indicated by the proportion of pts remaining alive & progression free [ Time Frame: 12 weeks from the start of testosterone treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To explore the association between AR expression in CRPC, as determined at baseline separately by AR FISH (performed on CTCs) and by 18F-FDHT uptake on PET scan, and progression free survival to the combination of testosterone plus dutasteride. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
To correlate post-treatment changes in CTCs and FDG and FDHT PET scans with post-treatment alterations in PSA and standard CT (or MRI) and bone scans. [ Time Frame: post treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	6
Study Start Date:	March 2009
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: testosterone with the 5α-reductase inhibitor dutast This trial is a multi-center, open-label, phase II trial of the combination of exogenous testosterone (AndroGel®) with the 5α-reductase inhibitor dutasteride in patients with castration-resistant metastatic prostate cancer.	Other: testosterone (AndroGel®) with the 5α-reductase inhibitor dutasteride Patients will be treated with dutasteride 3.5 mg once daily (oral administration). To avoid rapid conversion of testosterone to DHT in case 5α-reductase is not adequately inhibited during the first few days of concurrent treatment with dutasteride and testosterone, daily dutasteride treatment will be initiated 7 days prior to testosterone initiation. Patients will receive AndroGel® at the dose of 15 g (3 times the standard replacement dose for hypogonadism) once daily (topical administration), starting on Day 8 and continuing for 12 weeks (or until disease progression or withdrawal from the study). Other Names: Patients will be seen in clinic on day 8 and then on day 15±3, day 22±3, day 36±3 and during weeks 9 and 13 (±3 days), for a physical examination, safety assessments, and laboratory studies. Blood will be drawn at baseline, on day 8 and then on day 22±3, day 36±3 and during weeks 9 and 13 (±3 days), and at the completion of the study (week 13 or if patient is removed from study earlier) for the following assessments: CBC, comprehensive metabolic panel, PSA, testosterone, free testosterone, DHT, SHBG, LDH, lipid panel.

Arms

Assigned Interventions

Experimental: testosterone with the 5α-reductase inhibitor dutast

This trial is a multi-center, open-label, phase II trial of the combination of exogenous testosterone (AndroGel®) with the 5α-reductase inhibitor dutasteride in patients with castration-resistant metastatic prostate cancer.

Other: testosterone (AndroGel®) with the 5α-reductase inhibitor dutasteride

Patients will be treated with dutasteride 3.5 mg once daily (oral administration). To avoid rapid conversion of testosterone to DHT in case 5α-reductase is not adequately inhibited during the first few days of concurrent treatment with dutasteride and testosterone, daily dutasteride treatment will be initiated 7 days prior to testosterone initiation.

Patients will receive AndroGel® at the dose of 15 g (3 times the standard replacement dose for hypogonadism) once daily (topical administration), starting on Day 8 and continuing for 12 weeks (or until disease progression or withdrawal from the study).

Other Names:

Patients will be seen in clinic on day 8 and then on day 15±3, day 22±3, day 36±3 and
during weeks 9 and 13 (±3 days), for a physical examination, safety assessments,
and laboratory studies. Blood will be drawn at baseline, on day 8 and then on
day 22±3, day 36±3 and during weeks 9 and 13 (±3 days), and at the completion
of the study (week 13 or if patient is removed from study earlier) for the
following assessments: CBC, comprehensive metabolic panel, PSA, testosterone,
free testosterone, DHT, SHBG, LDH, lipid panel.

Eligibility

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

Criteria

Inclusion Criteria:

Patients should have histologically confirmed castration-resistant metastatic prostate cancer with evidence of disease progression. Patients must have been in a castrate state either by orchiectomy or by GnRH analogues for a minimum of one year. In detail, they should meet all of the following criteria:
Adult male > or = to 18 years of age
Histologically confirmed prostate cancer, currently with progressive disease, defined as rising PSA (50% or more increase to a level of 2 ng/mL or more, based on at least 3 PSA determinations obtained at least 1 weeks apart), or 2 new osseous lesions by bone scan, soft tissue disease progression by RECIST 1.1 criteria , or the appearance of new sites of disease (by MRI/CT).
Evidence of metastatic disease, documented within 4 weeks prior to dutasteride treatment initiation, based on a:
- CT or MRI of the abdomen and pelvis, and/or
- Radionuclide bone scan (in case of findings suspicious for spinal metastasis, MRI of the spine will be performed to rule out epidural disease)
Serum PSA ≥ 2 ng/mL within 4 weeks prior to dutasteride treatment initiation in order to register to the protocol
Normal organ function with acceptable initial laboratory values documented within 4 weeks prior to dutasteride treatment initiation:
- WBC > or = to 3000/µL
- Platelets > or = to 100,000/µL
- Creatinine < or = to 2 mg/dL
- Bilirubin < or = to 1.5 X ULN (institutional upper limits of normal)
- AST/ALT < or = to 2 X ULN
Karnofsky performance status > or = to 70%
Willingness to undergo serial blood draws for the purpose of measuring CTCs and other biomarkers. MSKCC patients will need to agree to participate in MSKCC protocol 90-040 Molecular studies and clinical correlations in human prostate cancer [PI: Scher]. Also, MSKCC patients will undergo serial imaging by FDHT and FDG PET scans, under protocol 00-095 [18f]-fluoro-2-deoxy-D-glucose and [18f]-dihydro-testosterone PET imaging in patients with progressive prostate cancer (PI: Morris), depending on tracer and scanner time availability. If the study is opened in other centers outside MSKCC, those centers will be exempt from procedures linked to the MSKCC Protocol # 00-095.
ADT treatment for at least 12 months prior to study entry with serum testosterone < 50 ng/dL.
Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

Patients meeting any of the following criteria will not be eligible for study entry:
Evidence of small-cell or neuroendocrine pathologic features
Uncontrolled urinary obstruction
Osseous metastatic disease with imminent risk (at the discretion of the treating physician) of pathologic fracture or cord compression (in patients with known spinal metastasis raising concern for cord compression, MRI of the spine should be performed to rule out epidural disease)
Any situation where, at the discretion of the treating physician, a potential "tumor flare" would be life-threatening
Sleep apnea (unless under good control with current treatment)
Polycythemia vera
History of allergic reactions attributed to compounds of similar chemical or biological composition to dutasteride
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situation that would compromise compliance with study requirements
Currently active secondary malignancy (as determined by the treating physician) other than non-melanoma skin cancer
Use of the following medications will be prohibited during the study:
- Current and/or previous use of the following medications:
- Finasteride (Proscar, Propecia) or dutasteride (GI198745, Avodart) exposure within 6 months of study entry.
- Anabolic androgenic steroids, including but not limited to testosterone, 17β testosterone esters, methyltestosterone, stanozolol, and danazol (within 6 months of study entry). Corticosteroids, including hydrocortisone, dexamethasone and prednisone are acceptable.
- Additional hormonal therapy within 4 weeks of study entry:
- Including megestrol, medroxyprogesterone, cyproterone, and DES
- Drugs with antiandrogenic properties (eg, spironolactone if > 50mg/d, flutamide, bicalutamide, nilutamide, ketoconazole,* progestational agents) * Includes topical ketoconazole.
Evidence of epidural disease by MRI

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853697

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

GlaxoSmithKline

University of Washington

Investigators

Principal Investigator:

Michael Morris, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00853697 History of Changes
Other Study ID Numbers:	09-008
Study First Received:	February 26, 2009
Last Updated:	February 3, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Prostate
DUTASTERIDE
TESTOSTERONE
09-008
Consortium Protocol LOI# c09-028

Additional relevant MeSH terms:

Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Dutasteride

Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
5-alpha Reductase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012