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Reolysin Combined With Docetaxel and Prednisone or Docetaxel and Prednisone Alone in Metastatic Castration Resistant Prostate Cancer

Phase 2
Completed
Conditions
Prostate Cancer
Interventions
Drug: Docetaxel, Reolysin and Prednisone
Registration Number
NCT01619813
Lead Sponsor
Canadian Cancer Trials Group
Brief Summary

The purpose of this study is to find out if giving Reolysin in combination with docetaxel and prednisone can offer better results than standard therapy with docetaxel and prednisone.

Detailed Description

Researchers doing this study also want to evaluate the side effects of Reolysin when given together with docetaxel and prednisone.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
85
Inclusion Criteria
  • 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 (measurable 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 eligible.
  • 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 following castration.

Progression is defined as one or both of the following:

PSA Progression:

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

Radiological Progression:

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

Surgery:

Previous major surgery is permitted provided that it has been at least 14 days prior to patient randomization and that wound healing has occurred.

Chemotherapy:

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 enrollment.

Hormonal Therapy:

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.

Radiation:

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 permitted.

  • Laboratory Requirements (must be done within 7 days prior to randomization)

Hematology:

Granulocytes (AGC) ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L

Biochemistry:

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 Proteinuria <2g/24hrs (screen using spot testing; if ≥ grade 2 repeat with mid-stream urine - if still ≥ grade 2 then urine collection for 24 hours to confirm <2g/24hrs)

  • 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.
Exclusion Criteria
  • 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 protocol.
  • Patients are not eligible if they have a known hypersensitivity to the study drug(s) or their components.
  • Patients with history of central nervous system metastases or untreated spinal cord compression.
  • 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Docetaxel, Reolysin and PrednisoneDocetaxel, Reolysin and Prednisone-
Docetaxel and PrednisoneDocetaxel and Prednisone-
Primary Outcome Measures
NameTimeMethod
Disease Progression12 weeks

Efficacy will be based on the lack of disease progression measured at 12 weeks.

Secondary Outcome Measures
NameTimeMethod
Effect of Docetaxel and Reolysin on circulating tumour cells12 weeks

Effect of docetaxel and Reolysin on the circulating tumour cell (CTC) favourable status (\< 5 CTC per 7.5mL). Effect will be measured after 6 and 12 weeks of treatment.

Objective Response24 months

Objective response rate (in patients with measurable disease at baseline)

Overall Survival24 months
Determine patient tolerability and toxicity of Reolysin and Docetaxel in combination24 months

Determine the effect of Reolysin and Docetaxel in combination in patients.

PSA change rate24 months
Prognostic/Predictive molecular response24 months

Explore potential molecular factors which might be prognostic/predictive of response (tumour, CTCs, serial blood samples).

Trial Locations

Locations (11)

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

Ottawa Hospital Research Institute

🇨🇦

Ottawa, Ontario, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

🇨🇦

Hamilton, Ontario, Canada

London Regional Cancer Program

🇨🇦

London, Ontario, Canada

BCCA - Cancer Centre for the Southern Interior

🇨🇦

Kelowna, British Columbia, Canada

BCCA - Abbotsford Centre

🇨🇦

Abbotsford, British Columbia, Canada

Cancer Centre of Southeastern Ontario at Kingston

🇨🇦

Kingston, Ontario, Canada

Allan Blair Cancer Centre

🇨🇦

Regina, Saskatchewan, Canada

BCCA - Fraser Valley Cancer Centre

🇨🇦

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

🇨🇦

Vancouver, British Columbia, Canada

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