Clinical Trials

Docetaxel and Prednisone With or Without Vaccine Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

Location:

Jacksonville,  FL,  Rochester,  MN

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES:

Primary

- To evaluate the overall survival of patients with castrate-resistant, metastatic prostate cancer treated with docetaxel and prednisone with versus without vaccine therapy comprising vaccinia-PSA(L155)-TRICOM and fowlpox-PSA(L155)-TRICOM.

Secondary

- To evaluate the time to radiographic progression in patients treated with these regimens.

- To compare objective response of patients with measurable disease treated with these regimens.

- To evaluate prostate-specific antigen (PSA) response rates (decline ≥ 50%) in patients treated with these regimens.

- To evaluate immune response elicited in patients before and after docetaxel chemotherapy.

- To evaluate the association between development of PSA-specific immune responses, time to progression, and overall survival in patients treated with these regimens.

- To evaluate the association of predicted survival (by Halabi nomogram) with actual survival of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to disease progression (PSA vs radiographic criteria), extraskeletal metastases (yes vs no), and prior bisphosphonate (yes vs no). Patients are randomized to 1 of 2 treatment arms.

- Arm I (vaccine and chemotherapy): Patients receive vaccinia-PSA(L155)-TRICOM vaccine subcutaneously (SC) on day 1 of course 1 and fowlpox-PSA(L155)-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel IV over 1 hour on day 1 and oral prednisone twice daily on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

- Arm II (chemotherapy): Patients receive docetaxel IV over 1 hour on day 1 and oral prednisone twice daily on days 1-21. Treatment with repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection to measure frequency of PSA-specific T-cells and other biomarkers of immune response.

After completion of study therapy, patients are followed up every 3-6 months for 5 years.

Who is eligible to participate?

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate

- Evidence of metastatic disease by the presence of soft tissue and/or bone metastases on CT scan of the abdomen and/or pelvis, or bone scintigraphy

- Castrate-resistant disease defined by the following:

- Must have received standard-of-care androgen-deprivation treatment (ADT) (e.g., surgical castration, gonadotropin-releasing hormone [GnRH], or antagonist treatment)

- Patients on concurrent GnRH analogue or antagonist must continue on this treatment throughout this study

- Must have been treated with nonsteroidal antiandrogen with evidence of subsequent disease progression

- Must have castration levels of testosterone (< 50 ng/dL) within the past 4 weeks

- Progressive disease while receiving ADT, defined by any 1 of the following:

- At least 2 consecutive rises in serum PSA (each value ≥ 2.0 ng/mL) obtained at a minimum of 1-week intervals

- Measurable disease with ≥ 50% increase in the sum of the cross products of all measurable lesions, or the development of new measurable lesions by RECIST

- The greatest diameter of a target lymph node must be ≥ 2 cm with conventional techniques or ≥ 1 cm by spiral CT scan

- Non-measurable (bone) disease consisting of ≥ 2 new areas of uptake by bone scan consistent with metastatic disease compared to previous imaging during castration therapy

- Ambiguous results must be confirmed by other imaging modalities (e.g., X-ray, CT scan, or MRI)

- Presence of visceral metastases

- No known brain metastases

PATIENT CHARACTERISTICS:

- Life expectancy ≥ 18 months by Halabi nomogram

- ECOG performance status 0-2

- WBC ≥ 2,000/mm^3

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Creatinine ≤ 2.0 mg/dL

- AST and ALT ≤ 1.5 times upper limit of normal

- Total bilirubin normal

- Fertile patients must agree to use effective contraception before, during, and for ≥ 4 months after completion of study therapy

- No known infection with HIV 1 or HIV 2, HTLV-1, hepatitis B, or hepatitis C, or any other potentially immunosuppressive infection

- Patients must have negative serologic testing for HIV, hepatitis B surface antigen, and hepatitis C

- No history of autoimmune disease requiring active immunosuppressive therapy or ≥ grade 2 organ dysfunction as a result of known autoimmune disease

- Patients must have antinuclear antibody (ANA) titer < 1:320

- No other active malignancy except nonmelanoma skin cancer, carcinoma in situ of the bladder, or other adequately treated cancer that has been free of recurrence for ≥ 3 years

- No allergy to eggs

- No known intolerance or allergic reactions to docetaxel or compounds of similar chemical or biologic composition

- No known history of allergic or intolerable reaction to vaccinia virus vaccination (e.g., smallpox)

- Patients or close household contacts of patients cannot have close contact with persons with the following conditions within 3 weeks after potential vaccinia immunization:

- History of eczema, active eczema or other acute, chronic, or exfoliative skin conditions, including Darier's disease (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or open wounds)

- Pregnant or nursing women

- Children under 3 years of age

- Immunodeficient or immunosuppressed persons (e.g., HIV infection, or treated for other diseases with immunosuppressive agents)

- Any other moderate or severe acute illness until the illness resolves

- None of the following conditions within the past 6 months:

- Stroke

- Myocardial infarction

- Unstable angina

- NYHA class II-IV congestive heart failure

- Significant cardiomyopathy requiring treatment

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 4 weeks since prior nonsteroidal antiandrogen (e.g., flutamide) (6 weeks for bicalutamide or nilutamide)

- At least 4 weeks since any prior treatment and recovered

- More than 4 weeks since prior and no concurrent therapy with any of the following:

- Other systemic corticosteroids

- Inhaled, intranasal, or topical corticosteroids allowed

- No steroid eyedrops at least 2 weeks before and 4 weeks after protocol vaccination

- PC-SPES

- Saw palmetto

- Megestrol

- Ketoconazole

- 5-α-reductase inhibitors

- Patients on 5-α-reductase inhibitors for > 28 days may continue these agents throughout the study

- May not start therapy with 5-α-reductase inhibitors during study therapy

- Diethyl stilbestrol

- Any other hormonal agent or supplement with possible anticancer activity

- More than 4 weeks since prior external-beam radiation therapy

- More than 4 weeks since surgery

- More than 6 months since prior chemotherapy

- Prior and/or concurrent bisphosphonates allowed

- More than 2 weeks since prior and no concurrent CYP3A4 substrates, inhibitors, or inducers

- No prior chemotherapy for metastatic prostate cancer

- No prior radiotherapy to > 30% of bone marrow

- No prior anticancer vaccine

- No prior splenectomy

- No other concurrent investigational agents or anticancer therapy other than androgen-deprivation treatment

Last updated: 03/26/2012

NCT ID:

NCT01145508