Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Samarium Sm 153 Lexidronam Pentasodium With or Without Vaccine Therapy in Treating Patients With Prostate Cancer and Bone Metastases

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Active	18 and over	NCI	NCI-07-C-0106 07-C-0106, 7678, NCT00450619

Special Category: NIH Clinical Center trial

Objectives

Primary

1. Compare the effect of samarium Sm 153 lexidronam pentasodium with or without recombinant fowlpox-TRICOM vaccine and recombinant vaccinia-TRICOM vaccine on the 4-month progression-free survival of patients with androgen-insensitive, prostate cancer metastatic to the bone.

Secondary

1. Compare immunologic response and prostate-specific antigen changes in patients treated with these regimens.
2. Compare response in patients treated with these regimens.
3. Compare the toxicity of these regimens in these patients.
4. Compare progression-free survival and overall survival of patients treated with these regimens.
5. Compare the relief of bone pain in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed prostate cancer
  • Metastatic androgen-insensitive disease
    • At least 2 bone lesions consistent with prostate cancer metastasis
  • Progressive disease, defined by 1 of the following criteria:
    • Two rising prostate-specific antigen (PSA) values separated by ≥ 1 week
    • New or enlarging lesions consistent with prostate cancer
    • Clinical progression
• Previously treated with docetaxel for metastatic disease, unless unable to tolerate docetaxel
• Concurrent medical castration therapy with testosterone-suppressing therapy (e.g., gonadotropin releasing hormone agonist) required unless patient has had prior surgical castration
• No symptomatic soft tissue disease or parenchymal disease
• No requirement for urgent local radiotherapy or orthopedic stabilization
• No brain metastasis

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from prior therapy, including surgery
• No prior recombinant fowlpox-TRICOM vaccine or recombinant vaccinia-TRICOM vaccine
• No prior samarium Sm 153 lexidronam pentasodium
• No prior splenectomy
• No chemotherapy within the past 4 weeks
• No radiotherapy to bone within the past 4 weeks
• No systemic steroid or steroid eye drops within the past 2 weeks
• No other concurrent therapy, including any of the following:
  • Chemotherapy or other anticancer treatment
  • Systemic glucocorticoids (topical or inhaled steroids allowed)
  • Radiotherapy
  • Major surgical procedures
  • Nonprotocol-related immunotherapy
• Concurrent bisphosphonates allowed except within 48 hours after radiotherapy

Patient Characteristics:

• ECOG performance status 0 or 1
• Life expectancy ≥ 6 months
• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• AST and ALT < 2.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 mg/dL (≤ 3.0 mg/dL in patients with Gilbert’s syndrome)
• Creatinine normal OR creatinine clearance > 60 mL/min
• Proteinuria < 1+ OR urine protein < 1,000 mg/24 hours
• Fertile patients must use effective contraception during and for 4 months after completion of study therapy
• No other active malignancies within the past 12 months except for nonmelanoma skin cancer or carcinoma in situ of the bladder
• No other life-threatening illnesses
• No evidence of being immunocompromised, including any of the following:
  • HIV positivity
  • Hepatitis B or C positivity
  • Concurrent use of topical steroids (including steroid eye drops) or systemic steroids
    • Nasal or inhaled steroids allowed
• No history of any of the following:
  • Cardiomyopathy or symptomatic congestive heart failure (unless on stable treatment)
  • Symptomatic arrhythmia not controlled by medication
  • Unstable atherosclerotic heart disease (e.g., unstable angina) or requirement for active intervention
  • Myocardial infarction or embolic stroke within the past 6 months
• No autoimmune diseases that require treatment, including any of the following:
  • Addison's disease
  • Hashimoto's thyroiditis
  • Systemic lupus erythematosus
  • Sjögren’s syndrome
  • Scleroderma
  • Myasthenia gravis
  • Goodpasture’s syndrome
  • Active Graves' disease
• History of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function (e.g., CNS, heart, lungs, kidneys, skin, or gastrointestinal tract) allowed
• No history of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen
  • Prior vaccination with vaccinia is not required
• No concurrent serious medical illness (e.g., one that requires treatment) that would preclude study treatment including, but not limited to, any of the following:
  • Inflammatory bowel disease
  • Crohn's disease
  • Ulcerative colitis
  • Active diverticulitis
• No history of seizures, encephalitis, or multiple sclerosis
• No cardiac disease accompanied by fatigue, palpitation, dyspnea, or angina with ordinary physical activity (i.e., New York Heart Association class II-IV disease)
• No history of congestive heart failure or objective evidence of congestive heart failure by physical exam or imaging, unless the underlying cause has been treated and patient has documented normal ejection fraction
• No pulmonary disease accompanied by fatigue or dyspnea with ordinary physical activity
• No serious hypersensitivity reaction to egg products
• No known hypersensitivity to EDTMP or similar phosphonate compounds
• No history of or active eczema or other eczematoid skin disorders
• No other acute, chronic, or exfoliative skin conditions, including any of the following:
  • Atopic dermatitis
  • Burns
  • Impetigo
  • Varicella zoster
  • Severe acne
  • Other open rashes or wounds
• Must be able to avoid close contact (e.g., share the same house or have close physical contact) with any of the following individuals for ≥ 3 weeks after treatment with the study vaccinia vaccine:
  • Individuals with a history of or active eczema or other eczematoid skin disorders
  • Individuals with other acute, chronic, or exfoliative skin conditions, including any of the following:
    • Atopic dermatitis
    • Burns
    • Impetigo
    • Varicella zoster
    • Severe acne
    • Other open rashes or wounds
  • Pregnant or nursing women
  • Children ≤ 3 years of age
  • Immunodeficient or immunosuppressed individuals by disease or therapy, including HIV positive individuals
• Willing to travel to the National Institutes of Health or participating institution for follow up visits
• Patients who are incontinent of urine must be willing to undergo bladder catheterization

Expected Enrollment

A total of 68 patients will be accrued for this study.

Outcomes

4-month progression-free survival

Objective response
Prostate-specific antigen outcomes
Immunologic response
Toxicity
Progression-free and overall survival
Bone pain

Outline

This is a multicenter, randomized, open-label, pilot study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive samarium Sm 153 lexidronam pentasodium (¹⁵³SM-EDTMP) IV over 1 minute on day 8. Treatment repeats every 12 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive recombinant vaccinia-TRICOM vaccine subcutaneously (SC) on day 1. Patients also receive recombinant fowlpox-TRICOM vaccine SC on days 15 and 29 and sargramostim (GM-CSF)* SC on days 1-4, 15-18, 29-32. Treatment with recombinant fowlpox-TRICOM vaccine and GM-CSF* repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ¹⁵³SM-EDTMP as in arm I.

   [Note: *Patient no longer receive GM-CSF as of 3/4/09.]

Some patients (only patients enrolled at The National Institutes of Health) who are HLA-A2-positive undergo apheresis for immunological studies. Blood serum is analyzed for interferon gamma-releasing T cells specific to prostate-specific antigen (PSA)-3A as measured by ELISPOT assay as well as antibodies to PSA, vaccinia, fowlpox, and antinuclear antibody titer**.

 [Note: **Antinuclear antibody titer no longer analyzed as of 3/4/2009.]

Bone pain is assessed periodically.

After completion of study treatment, patients are followed periodically for up to 15 years.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

James Gulley, MD, PhD, FACP, Principal investigator		Ph: 301-435-2956 Email: gulleyj@mail.nih.gov

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Registry Information
Official Title		A randomized phase 2.5 study of 153Sm-EDTMP (Quadramet) with or without a PSA/TRICOM vaccine in men with androgen-insensitive metastatic prostate cancer
Trial Start Date		2007-02-14
Trial Completion Date		2009-12-01 (estimated)
Registered in ClinicalTrials.gov		NCT00450619
Date Submitted to PDQ		2007-02-02
Information Last Verified		2009-06-14

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