Samarium-153 With Neoadjuvant Hormonal and Radiation Therapy for Locally Advanced Prostate Cancer - Full Text View

Purpose

The purpose of this study is to determine the safety and effectiveness of Samarium-153 when given in combination with hormonal and external beam radiation therapy in men with high risk prostate cancer.

Condition	Intervention	Phase
Prostate Cancer	Drug: Samarium-153 Drug: Total Androgen Suppression (TAS) with Bicalutamide Drug: Total androgen suppression (TAS) with Goserelin Acetate Device: Radiation Therapy	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Pilot Study of Samarium-153 Combined With Neoadjuvant Hormonal Therapy and Radiation Therapy in Men With Locally Advanced Prostate Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: prostate cancer

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Goserelin Bicalutamide Goserelin acetate

U.S. FDA Resources

Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:

Maximum Tolerated Dose of Samarium-153 [ Time Frame: 5 months (1 month HT, administration of drug, 4 months HT and RT) ] [ Designated as safety issue: Yes ]
To determine the maximum tolerated dose (MTD) of Samarium as adjuvant to combined hormonal therapy (HT) and external beam radiation therapy (RT).

Dose levels:

Dose I: 0.25 mCi/kg IV Dose II: 0.5 mCi/kg IV Dose III: 0.75 mCi/kg IV Dose IV: 1.0 mCi/kg IV Dose V: 1.5 mCi/kg IV Dose VI: 2.0 mCi/kg IV

Dose-limiting toxicity will be defined as Grade 3 hematologic toxicity per NCI Common Toxicity Criteria. The maximally tolerated dose (MTD) will then be the last dose studied or the previous dose, based on clinical judgment of the degree of toxicity seen at the last dose.


Enrollment:	32
Study Start Date:	March 2003
Study Completion Date:	June 2011
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Samarium-153 (0.25 mCi/kg) Cohort 1: Patients receive 0.25 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy	Drug: Samarium-153 Samarium-153 will be administered as a single dose after one month of hormonal therapy. The dose level of Samarium-153 may change to determine maximum tolerated dose (MTD). Other Names: Samarium-153-ethylene diamine tetramethylene phosphonate Samarium (153Sm) lexidronam Quadramet Drug: Total Androgen Suppression (TAS) with Bicalutamide Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Casodex Drug: Total androgen suppression (TAS) with Goserelin Acetate Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Zoladex Device: Radiation Therapy Radiation therapy will begin 3 months following the initiation of hormone administration. Daily tumor doses will be given 5 days per week for 7-8 weeks. Other Names: XRT Radiotherapy
Experimental: Samarium-153 (0.5 mCi/kg) Cohort 2: Patients receive 0.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy	Drug: Samarium-153 Samarium-153 will be administered as a single dose after one month of hormonal therapy. The dose level of Samarium-153 may change to determine maximum tolerated dose (MTD). Other Names: Samarium-153-ethylene diamine tetramethylene phosphonate Samarium (153Sm) lexidronam Quadramet Drug: Total Androgen Suppression (TAS) with Bicalutamide Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Casodex Drug: Total androgen suppression (TAS) with Goserelin Acetate Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Zoladex Device: Radiation Therapy Radiation therapy will begin 3 months following the initiation of hormone administration. Daily tumor doses will be given 5 days per week for 7-8 weeks. Other Names: XRT Radiotherapy
Experimental: Samarium-153 (0.75 mCi/kg) Cohort 3: Patients receive 0.75 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy	Drug: Samarium-153 Samarium-153 will be administered as a single dose after one month of hormonal therapy. The dose level of Samarium-153 may change to determine maximum tolerated dose (MTD). Other Names: Samarium-153-ethylene diamine tetramethylene phosphonate Samarium (153Sm) lexidronam Quadramet Drug: Total Androgen Suppression (TAS) with Bicalutamide Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Casodex Drug: Total androgen suppression (TAS) with Goserelin Acetate Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Zoladex Device: Radiation Therapy Radiation therapy will begin 3 months following the initiation of hormone administration. Daily tumor doses will be given 5 days per week for 7-8 weeks. Other Names: XRT Radiotherapy
Experimental: Samarium-153 (1.0 mCi/kg) Cohort 4: Patients receive 1.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy	Drug: Samarium-153 Samarium-153 will be administered as a single dose after one month of hormonal therapy. The dose level of Samarium-153 may change to determine maximum tolerated dose (MTD). Other Names: Samarium-153-ethylene diamine tetramethylene phosphonate Samarium (153Sm) lexidronam Quadramet Drug: Total Androgen Suppression (TAS) with Bicalutamide Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Casodex Drug: Total androgen suppression (TAS) with Goserelin Acetate Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Zoladex Device: Radiation Therapy Radiation therapy will begin 3 months following the initiation of hormone administration. Daily tumor doses will be given 5 days per week for 7-8 weeks. Other Names: XRT Radiotherapy
Experimental: Samarium-153 (1.5 mCi/kg) Cohort 5: Patients receive 1.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy	Drug: Samarium-153 Samarium-153 will be administered as a single dose after one month of hormonal therapy. The dose level of Samarium-153 may change to determine maximum tolerated dose (MTD). Other Names: Samarium-153-ethylene diamine tetramethylene phosphonate Samarium (153Sm) lexidronam Quadramet Drug: Total Androgen Suppression (TAS) with Bicalutamide Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Casodex Drug: Total androgen suppression (TAS) with Goserelin Acetate Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Zoladex Device: Radiation Therapy Radiation therapy will begin 3 months following the initiation of hormone administration. Daily tumor doses will be given 5 days per week for 7-8 weeks. Other Names: XRT Radiotherapy
Experimental: Samarium-153 (2.0 mCi/kg) Cohort 6: Patients receive 2.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy	Drug: Samarium-153 Samarium-153 will be administered as a single dose after one month of hormonal therapy. The dose level of Samarium-153 may change to determine maximum tolerated dose (MTD). Other Names: Samarium-153-ethylene diamine tetramethylene phosphonate Samarium (153Sm) lexidronam Quadramet Drug: Total Androgen Suppression (TAS) with Bicalutamide Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Casodex Drug: Total androgen suppression (TAS) with Goserelin Acetate Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation. Other Name: Zoladex Device: Radiation Therapy Radiation therapy will begin 3 months following the initiation of hormone administration. Daily tumor doses will be given 5 days per week for 7-8 weeks. Other Names: XRT Radiotherapy

Detailed Description:

The likelihood of prostate cancer cells metastasizing to bone has an early and important influence on the natural history of prostate cancer. Bone-targeted therapy, when given sequentially with hormonal therapy (androgen suppression) and radiation therapy, prolongs the progression of the disease in clinically non-metastatic prostate cancer patients.

The use of Samarium-153 EDTMP in conjunction with hormonal therapy and external beam radiation therapy has never been previously evaluated in high risk clinically localized prostate cancer. Many patients with high-risk prostate cancer develop progressive disease within 2 years of therapy indicating that subclinical metastatic disease may be present at the time of initial diagnosis. In these high-risk patients, there may be a therapeutic benefit of combining hormonal therapy with external beam radiation therapy and Samarium-153 EDTMP to treat localized and subclinical bony disease, respectively.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

PSA 20-150 and Gleason score greater than or equal to 7 or clinical stage greater than or equal to T2, Gleason greater than or equal to 8, PSA less than or equal to 150
Pathologically positive lymph nodes
Pretreatment must be prior to study entry and prior to any hormonal therapy
Zubrod 0-1
Adequate hematologic function

Exclusion Criteria:

Patients with PSA equal to or greater than 150
Neuroendocrine features on histologic examination
Radiologic evidence of metastatic disease
Previous malignancy within last 5 years
Prior pelvic radiation therapy or orchiectomy

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00328614

Locations


United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Thomas Jefferson University

Cytogen Corporation

Investigators


Principal Investigator:	Edouard Trabulsi, MD	Thomas Jefferson University
Study Chair:	Richard Valicenti, MD, MA	UC Davis School of Medicine

More Information

Additional Information:

Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center This link exits the ClinicalTrials.gov site

Thomas Jefferson University Hospitals This link exits the ClinicalTrials.gov site


Responsible Party:	Thomas Jefferson University
ClinicalTrials.gov Identifier:	NCT00328614 History of Changes
Other Study ID Numbers:	02C.172 2001-114
Study First Received:	May 19, 2006
Results First Received:	June 24, 2013
Last Updated:	November 11, 2013
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Keywords provided by Thomas Jefferson University:


Locally advanced prostate cancer positive lymph nodes

Additional relevant MeSH terms:


Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Prostatic Diseases Androgens Ascorbic Acid Estrogens, Conjugated (USP) Methyltestosterone Goserelin Bicalutamide Samarium ethylenediaminetetramethylenephosphonate Hormones	Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Vitamins Micronutrients Growth Substances Estrogens Antineoplastic Agents, Hormonal Antineoplastic Agents Anabolic Agents Androgen Antagonists Hormone Antagonists Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on September 26, 2016