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

PRIMARY OBJECTIVES:

I. To evaluate the overall survival in patients treated with PSA-TRICOM (fowlpox-PSA-TRICOM
vaccine and rilimogene-galvacirepvec) and docetaxel chemotherapy versus docetaxel
chemotherapy only.

SECONDARY OBJECTIVES:

I. To evaluate the time to radiographic progression after beginning docetaxel chemotherapy
in patients previously treated with PSA-TRICOM vaccine versus those not treated with this
vaccine.

II. To compare objective responses (according to Response Evaluation Criteria in Solid
Tumors [RECIST]) between the two treatment groups in those patients with measurable disease.

III. To evaluate prostate-specific antigen (PSA) response rates (decline >= 50%) in patients
treated with PSA-TRICOM and docetaxel chemotherapy versus docetaxel chemotherapy only.

IV. To evaluate immune responses elicited in patients treated before and after docetaxel
chemotherapy.

V. To evaluate the association between development of prostate antigen-specific immune
responses and time to progression and overall survival.

VI. To evaluate the association of predicted survival (by Halabi nomogram) with actual
survival in patients treated with PSA-TRICOM vaccine versus those not treated with this
vaccine.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A (vaccine and chemotherapy): Patients receive rilimogene-galvacirepvec subcutaneously
(SC) on day 1 of course 1 and fowlpox-PSA-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 intravenously
(IV) over 1 hour on day 1 and prednisone orally (PO) twice daily (BID) 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 B (chemotherapy): Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO
BID on days 1-21. Treatment repeats every 21 days for up to 12 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

Inclusion Criteria:

- Patient must have histologically confirmed diagnosis of prostate cancer
(adenocarcinoma of the prostate)

- Patient must have metastatic disease as evidenced by the presence of soft tissue
and/or bone metastases on imaging studies (computed tomography [CT] of
abdomen/pelvis, bone scintigraphy)

- Patient must have castrate-resistant disease, defined as follows:

- Patient must have received standard of care androgen deprivation treatment (ADT)
before trial entry (surgical castration versus gonadotropin-releasing hormone
[GnRH] analogue or antagonist treatment); subjects receiving GnRH analogue or
antagonist must continue this treatment throughout the time on this study

- Patient must have been treated previously with a nonsteroidal antiandrogen, with
evidence of subsequent disease progression; subjects must be off use of
anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide
or nilutamide) prior to randomization; subjects who demonstrate an anti-androgen
withdrawal response, defined as a >= 25% decline in PSA within 4-6 week of
stopping a nonsteroidal antiandrogen are not eligible until the PSA rises above
the nadir observed after antiandrogen withdrawal

- Patient must have castration levels of testosterone (< 50 ng/dL) within 4 weeks
prior to randomization

- Patient must have progressive disease while receiving ADT as defined by any one of
the following as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2)
criteria:

- PSA: at least two consecutive rises in serum PSA, obtained at a minimum of
1-week intervals, and each value >= 2.0 ng/mL

- Measurable disease: >= 50% increase in the sum of the cross products of all
measurable lesions or the development of new measurable lesions by RECIST
criteria version 1.1; the greatest diameter of a target lesion must be at least
1.0 cm by CT scan (1.5 cm in shortest axis for lymph nodes)

- Non-measurable (bone) disease: the appearance of two or more new areas of uptake
on bone scan consistent with metastatic disease compared to previous imaging
during castration therapy; the increased uptake of pre-existing lesions on bone
scan will not be taken to constitute progression, and ambiguous results must be
confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance
imaging [MRI])

- Patient must not have poor prognosis features suggested by the following required
information:

- Presence of visceral (non-lymph node, non-bone) metastases

- Poor performance status (Eastern Cooperative Oncology Group [ECOG] performance
status [PS] of 2 or greater)

- Alkaline phosphatase (IU/L) > 2 x institutional upper limit of normal

- Lactate dehydrogenase (LDH) (U/L) > 2 x institutional upper limit of normal

- Patient must have an ECOG performance status of 0 or 1

- White blood cell (WBC) count >= 2000/mm^3

- Absolute neutrophil count (ANC) >= 1500/mm^3

- Platelet count >= 100,000/mm^3

- Creatinine =< 2.0 mg/dL

- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 x
institutional upper limit of normal (ULN)

- Total bilirubin < institutional upper limit of normal (ULN)

- Patient must have completed any prior treatments (apart from androgen deprivation as
previously described) >= 4 weeks prior to randomization and have recovered (to <
grade 2) from any acute toxicities attributed to this prior treatment

- Patient must agree to use an accepted and effective method of contraception prior to
study entry and for the duration of study participation (or at least 4 months after
the last vaccination in subjects receiving vaccine series); if patient impregnates a
woman while participating in this study, he should inform his treating physician
immediately

- Patient must not be receiving any other investigational agents or be receiving
concurrent anticancer therapy other than ADT

- Patient must not have been treated with a prior anti-cancer vaccine (including
sipuleucel-T, Provenge®)

- Patient must not have received treatment with any of the following medications within
4 weeks of randomization or while on study:

- Systemic corticosteroids (excluding prednisone and dexamethasone administered as
part of study protocol); inhaled, intranasal or topical corticosteroids are
acceptable; steroid eye drops are contraindicated however, for 2 weeks prior to
vaccination and for at least 4 weeks after vaccinia vaccination

- PC-SPES

- Saw palmetto

- Megestrol

- Ketoconazole

- 5-alpha-reductase inhibitors - patients already taking 5-alpha-reductase
inhibitors prior to 28 days prior to randomization may stay on these agents
throughout the course of therapy, but these should not be started while patients
are on study

- Diethyl stilbestrol

- Any other hormonal agent or supplement with possible anti-cancer activity

- Patient must not have been treated with external beam radiation therapy within 4
weeks of randomization

- Patient must not have received prior radiation therapy to > 30% of bone marrow

- Patient must not have had surgery within 4 weeks of randomization

- Patient must not have received prior chemotherapy within 6 months of randomization;
prior and/or concurrent treatment with bisphosphonates, however, is permitted

- Patient must not have received prior chemotherapy for metastatic prostate cancer

- Patient cannot have a known history of human immunodeficiency virus (HIV) 1 or 2,
human T-lymphotropic virus (HTLV)-1, hepatitis B, or hepatitis C (or any other
potentially immunosuppressive infection); eligible subjects must have negative
serologic testing for HIV, hepatitis B surface antigen, and hepatitis C

- Patient cannot have a history of autoimmune disease requiring active
immunosuppressive therapy or have organ dysfunction >= grade 2 as a result of known
autoimmune disease; eligible subjects must have antinuclear antibodies (ANA) titer <
1:320

- Patient must not have undergone splenectomy

- Patient must not have other active malignancies other than non-melanoma skin cancers
or carcinoma in situ of the bladder; subjects with a history of other cancers who
have been adequately treated and have been recurrence-free for >= 3 years are
eligible

- Patient cannot have a known allergy to eggs

- Patient cannot have a known intolerance or allergic reactions to docetaxel or
compounds of similar chemical or biologic composition

- Patient cannot have a known history of allergy or intolerable reaction to a previous
vaccinia virus vaccination (e.g., smallpox)

- Patient or close household contacts of patient (those who share housing or have close
physical contact with the patient) cannot have close physical contact to persons with
the following conditions within 3 weeks after potential vaccinia immunization:

- A 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, or treated for other
diseases with immunosuppressive agents)

- Any other moderate or severe acute illness until the illness resolves Patients
who would be unable to avoid these conditions for a 3-week period are not
eligible; patients should also refer to the patient instruction sheet for
vaccinia virus

- Patient cannot have known brain metastases

- Patient cannot have a known history of recent (within 6 months) stroke, myocardial
infarction, unstable angina, New York Heart Association class II-IV congestive heart
failure, or significant cardiomyopathy requiring treatment

- Patient cannot take known strong inducers or inhibitors of cytochrome P450, family 3,
subfamily A, polypeptide 4 (CYP3A4) within 2 weeks of beginning docetaxel through its
discontinuation; substrates of CYP3A4 with a narrow therapeutic/toxicity window may
be used with caution, with prior approval of the study chair or institution's
principal investigator (PI)