A Randomized Phase II Study of Reolysin in Combination With Docetaxel and Prednisone or Docetaxel and Prednisone Alone in Patients With Metastatic Castration Resistant Prostate Cancer
- Patients must have a histological diagnosis of adenocarcinoma of the prostate.
- All patients must have a formalin fixed paraffin embedded tissue block (from their
primary or metastatic tumour) available for translational studies.
- Presence of clinically and/or radiologically documented disease (measureable or
non-measurable). All radiology studies must be performed within 28 days prior to
randomization (within 35 days if negative). Patients with elevated PSA only are not
- Androgen ablation must include either medical or surgical castration. If the patient
is receiving medical androgen ablation, a castrate level of testosterone (< 1.7
nmol/L) must be present.
- Patients must have metastatic or locally recurrent disease, for which no curative
therapy exists and for which systemic therapy is indicated due to progression
Progression is defined as one or both of the following:
A rising PSA, while receiving androgen ablative therapy, with 2 subsequent rises over a
reference value (not necessarily consecutively), measured a minimum of one week apart. The
PSA that confirms progression must have a value of ≥2 ng/ml and must be performed no
longer than 7 days prior to trial randomization. Patients who have had prolonged responses
to combined androgen blockade should be evaluated for a withdrawal response prior to
confirming eligibility OR
defined as the development of new metastatic lesions or progression in target disease
(RECIST 1.1) with a stable or rising PSA.
- The PSA must be ≥ 5 ng/ml at the time of study entry.
- ECOG performance of 0, 1 or 2.
- Age ≥ 18 years of age.
- Patients must have a life expectancy of ≥ 12 weeks.
- Previous Therapy
Previous major surgery is permitted provided that it has been at least 14 days prior to
patient randomization and that wound healing has occurred.
Patients may NOT have received any prior cytotoxic chemotherapy for recurrent/metastatic
castration resistant prostate cancer. Prior docetaxel treatment is not permitted unless it
was provided on an adjuvant therapy protocol more than 12 months prior to study enrolment.
Prior hormone therapy is required. Patients must be castrate resistant and have
discontinued anti-androgens for at least 4 weeks prior to study entry (at least 6 weeks
for bicalutamide). Therapy with LHRH agonist must continue for those prostate cancer
patients already receiving this treatment at the time of enrollment. If the patient has
discontinued the LHRH agonist, this must be restarted (if not surgically castrated) and
the castrate level of testosterone must be present. Prior therapy with CYP17 inhibitors
(e.g. abiraterone, ketoconazole) or novel anti-androgens (e.g. MDV3100) is permitted.
Prior external beam radiation is permitted provided a minimum of 4 weeks has elapsed
between the last dose and enrollment to the trial. Exceptions may be made for low dose,
non-myelosuppressive radiotherapy after consultation with NCIC CTG. Prior strontium is not
- Laboratory Requirements (must be done within 7 days prior to randomization)
Granulocytes (AGC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L
Serum creatinine ≤ 1.5 x ULN Total bilirubin ≤ 1.0 x ULN (unless elevated secondary to
conditions such as Gilbert's disease) ALT and AST ≤ 1.5 x ULN
- Patient consent must be appropriately obtained in accordance with applicable local
and regulatory requirements. Each patient must sign a consent form prior to
enrollment in the trial to document their willingness to participate.
Patients who cannot give informed consent (i.e. mentally incompetent patients, or those
physically incapacitated such as comatose patients) are not to be recruited into the
study. Patients competent but physically unable to sign the consent form may have the
document signed by their nearest relative or legal guardian. Each patient will be provided
with a full explanation of the study before consent is requested.
- Patients must be accessible for treatment and follow-up. Patients registered on this
trial must be treated and followed at the participating centre. This implies there
must be reasonable geographical limits (for example: 2 hour's driving distance)
placed on patients being considered for this trial. Investigators must assure
themselves that the patients registered on this trial will be available for complete
documentation of the treatment, adverse events, response assessment and follow-up.
- In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working
days of patient randomization.
- Patients with a history of other malignancies, except for adequately treated
non-melanoma skin cancer or solid tumours curatively treated with no evidence of
disease for ≥ 3 years.(Please call NCIC CTG if any questions about the interpretation
of this criterion).
- Patients who are on immunosuppressive therapy or have known HIV infection or active
hepatitis B or C.
- Patients with active or uncontrolled infections, or with serious illnesses or medical
conditions which would not permit the patient to be managed according to the
- Patients are not eligible if they have a known hypersensitivity to the study drug(s)
or their components, or are unable to discontinue therapy with acetaminophen.
- Patients with history of central nervous system metastases or untreated spinal cord
- Patients who have had prior treatment with docetaxel for advanced/metastatic disease.
- Men who are not sterile unless they use an adequate method of birth control.