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

Alternate Title

SB-715992 in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Docetaxel or Paclitaxel

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI SWOG-S0418 S0418, NCT00096499

Objectives

Primary

1. Determine the prostate-specific antigen response to SB-715992 in patients with hormone-refractory, androgen-independent metastatic prostate cancer that failed prior taxane-based chemotherapy.

Secondary

1. Determine the median overall survival and median progression-free survival of patients treated with this drug.
2. Determine the objective response rate (confirmed and unconfirmed, complete and partial response) in patients with measurable disease treated with this drug.
3. Determine the qualitative and quantitative toxic effects of this drug in these patients.
4. Determine, preliminarily, the pharmacokinetics and mechanism of activity of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the prostate
  • Metastatic disease (N1 and/or M1)
  • Unresponsive or refractory to androgen-deprivation therapy



• Must have received one, and only one, prior taxane-containing (docetaxel or paclitaxel) chemotherapy regimen for metastatic disease that was discontinued due to disease progression, intolerance, or patient request



• Evidence of disease progression as defined by ≥ 1 of the following:
  • Progression of measurable disease
  • Progression of evaluable disease
  • Rising prostate-specific antigen (PSA)
    • At least 2 consecutive rises in PSA levels, each taken ≥ 7 days apart
    • PSA ≥ 5 ng/mL



• Must have pre-study PSA > 5 ng/mL



• Measurable or evaluable disease
  • Soft tissue disease that has been irradiated within the past 2 months is not considered measurable disease
  • Soft tissue disease that has been irradiated ≥ 2 months prior to study entry is considered measurable disease provided the lesion progressed after radiation



• Surgical or medical castration required
  • If luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or LHRH antagonists (abarelix) were used, then must continue use during study therapy



• No prior or concurrent brain metastases (treated or untreated)
  • If clinical suspicion of brain metastases, must meet the following criteria:
    • Brain CT scan or MRI negative for metastatic disease within the past 56 days
    • No new symptoms since radiographic evaluation

Prior/Concurrent Therapy:

Biologic therapy

• No colony-stimulating factors during the first course of study therapy
• No concurrent anticancer biologic therapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior flutamide or ketoconazole
• At least 6 weeks since prior bicalutamide or nilutamide
• No concurrent anticancer hormonal therapy except LHRH agonist or antagonist for patients who have not undergone orchiectomy

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• Prior samarium Sm 153 lexidronam pentasodium allowed
• No prior strontium chloride Sr 89
• No prior radiotherapy to ≥ 30% of bone marrow
• No concurrent anticancer radiotherapy

Surgery

• See Disease Characteristics
• At least 3 weeks since prior surgery and recovered

Other

• At least 2 weeks since prior and no concurrent use of any of the following CYP3A4 inhibitors or inducers:
  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Rifampin
  • Rifabutin
  • Rifapentine
  • Itraconazole
  • Ketoconazole
  • Fluconazole (dose > 200 mg/day)
  • Voriconazole
  • Nefazodone
  • Fluvoxamine
  • Verapamil
  • Diltiazem
  • Grapefruit juice
  • Bitter orange
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Oxcarbazepine
  • Hypericum perforatum (St. John's wort)
  • Modafinil
• At least 6 months since prior and no concurrent amiodarone
• No other investigational drugs for 4 weeks before, during, and for 2 weeks after study therapy
• No other concurrent anticancer cytotoxic therapy
• No other concurrent anticancer therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• Concurrent enrollment on SWOG-9205 (central prostate cancer serum repository protocol) allowed

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL

Hepatic

• Bilirubin normal
• SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

  OR

• Creatinine clearance ≥ 40 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Fertile patients must use effective contraception
• No peripheral neuropathy ≥ grade 2
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to SB-715992
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other uncontrolled illness
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated stage I or II cancer in complete remission

Expected Enrollment

A total of 20-40 patients will be accrued for this study within 1.3-2.7 months.

Outcomes

Prostate-specific antigen response rate every 3 weeks

Objective response rate as measured by RECIST every 6 weeks
Adverse events as measured by CTC every 3 weeks
Biomarkers measured continuously

Outline

This is a multicenter study.

Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Tomasz Beer, MD, Protocol chair		Ph: 503-494-3253; 800-494-1234
Christopher Ryan, MD, Protocol co-chair		Ph: 503-220-8262

Registry Information
Official Title		A Phase II Study Of SB-715992 (NSC-727990) In Taxane-Resistant Androgen-Independent Metastatic Prostate Cancer
Trial Start Date		2005-04-01
Registered in ClinicalTrials.gov		NCT00096499
Date Submitted to PDQ		2004-09-16
Information Last Verified		2005-11-07
NCI Grant/Contract Number		CA32102