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Activity of TroVax® Alone vs. TroVax® Plus GM-CSF in Patients With Prostate Cancer

Phase 2
Completed
Conditions
Prostatic Neoplasms
Interventions
Biological: TroVax
Registration Number
NCT00448409
Lead Sponsor
The Methodist Hospital Research Institute
Brief Summary

To evaluate the efficacy and safety of Trovax and GM-CSF in patients with prostate cancer.

Detailed Description

Prostate cancer is the second leading cause of cancer death in American men. Hormonal ablation, in the form of medical or surgical castration is the cornerstone of management for metastatic prostate cancer however, treatment options for a patient in whom androgen ablation fails are limited. Second-line hormonal agents are generally associated with low response rates and no documented survival benefit.

Historically, chemotherapy was not considered to have significant activity in hormone refractory prostate cancer (HRPCa). This view has changed within the past 10 years, partly because of the availability of prostate-specific antigen (PSA) measurements to monitor tumor burden. Although it seems that chemotherapy, either as a single agent or combination of agents may lead to clinical responses, reduction in PSA measurements, pain control, or improved quality of life, no benefit in overall survival has been definitively proven. The current standard of care for the treatment of metastatic prostate cancer is hormone therapy (androgen blockade).3,4 When this strategy is no longer effective, few good treatment options are left. For this reason, prostate cancer research has aimed to identify new therapeutic modalities to increase the impact of these parameters as well as prolong patient survival.

A total of 24 men with prostate cancer ranging from non-metastatic rising PSA only disease to bony metastatic disease will be enrolled in the study. All patients will have failed androgen treatment and at least one prior taxane chemotherapy or have refused chemotherapy.

Out of the 24 patients, 12 patients will be treated using TroVax® and 12 will be treated using TroVax® plus GM-CSF.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
27
Inclusion Criteria
  • Histologically confirmed adenocarcinoma of the prostate.
  • Stable or progressive disease after androgen deprivation.
  • Karnofsky Performance Status ≥ 60%.
  • At least one prior taxane based chemotherapy for prostate cancer therapy (or patient refusal of chemotherapy)
  • At least four weeks have lapsed since prior chemotherapy (if administered)
  • Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy within one month prior to starting therapy or throughout the study.
  • Major surgery or radiation therapy completed ≥ 4 weeks prior to enrollment.
  • Clinically immunocompetent. All patients are assumed to be immunocompetent unless they have been diagnosed as being immunosuppressed, are receiving oral steroids, immunosuppressive chemotherapy for oncology disorders or are receiving immunosuppressive therapy following transplant.
  • Free of clinically apparent autoimmune disease (no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's disease, Hashimoto's thyroiditis, multiple sclerosis, insulin dependant diabetes mellitus or systemic (non-joint) manifestations of rheumatoid disease).
  • Absolute Lymphocyte Count ≥ 500/µl, ANC >1200/µl, Platelet count >100,000/µl, Hemoglobin > 8 mg/dl
  • No evidence of active ischemia on ECG
Exclusion Criteria
  • Patients receiving any other hormonal therapy, including any dose of megestrolacetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid must discontinue the agent for at least 4 weeks prior to enrollment. Progressive disease (as defined above) must be documented after discontinuation of the hormonal therapy.
  • Patients that initiate bisphosphonate therapy within one month prior to starting therapy or throughout the study.
  • No supplements or complementary medicines/botanicals are permitted during the study
  • Major surgery or radiation therapy completed ≤ 4 weeks prior to enrollment.
  • Prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment.
  • "Currently active" second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse.
  • Serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled.
  • Psychiatric illnesses/social situations that would limit compliance with protocol requirements.
  • Liver function tests (ALT, AST) more than 1.5 x upper limit of normal (ULN). The bilirubin must be within normal limits.
  • Renal function creatinine ≥1.5 x ULN.
  • Known allergy to egg proteins.
  • Known allergy to neomycin.
  • History of allergic response to previous vaccinia vaccinations.
  • Chronic oral corticosteroid use (especially anti-emetics) unless prescribed as replacement therapy in the case of adrenal insufficiency.
  • Known to test positive for HIV or hepatitis B or C.
  • Clinical indication of reduced cardiac function or an ejection fraction of ≤ 40%.
  • Requirement for radiotherapy (this is a sign of disease progression and is classed as a withdrawal criterion).
  • Concurrent chemotherapy, immunotherapy and radiation therapy
  • No investigational or commercial agents or therapies other than those included in protocol treatment may be administered with the intent to treat the patient's malignancy.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1TroVaxTroVax alone
2TroVaxTroVax plus GM-CSF
2GM-CSFTroVax plus GM-CSF
Primary Outcome Measures
NameTimeMethod
CD8+ve cellular response to 5T4 antigen as measured by Elispotat end of study
Assessment of the number of adverse events and serious adverse events in both groupsAEs as occur
Anti-5T4 antibody levels1st 2 cycles every 2 wks; thereafter about every 4 wks
PSA response rate to TroVax® and TroVax® in combination with GM-CSFrestaging every 8 weeks
Secondary Outcome Measures
NameTimeMethod
Progression-free survivalrestaging every 8 weeks
Objective response raterestaging every 8 weeks
Overall survival of the patientsrestaging every 8 weeks
Time to progressionrestaging every 8 weeks

Trial Locations

Locations (1)

The Methodist Hospital Research Institute

🇺🇸

Houston, Texas, United States

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