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

This study has been completed.
Sponsor:
Collaborator:
Cytogen Corporation
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00328614
First received: May 19, 2006
Last updated: November 11, 2013
Last verified: November 2013
  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:


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
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:
No publications provided

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
Samarium ethylenediaminetetramethylenephosphonate
Goserelin
Bicalutamide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Androgen Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on July 20, 2014