Clinical trial NCT01603420: External Beam Radiation With or Without Chemotherapy to Treat High Risk Prostate Cancer
Official title: Phase 2/3 Study of Dose-escalated External Beam Radiation Therapy With or Without Chemotherapy for High Risk Adenocarcinoma of the Prostate
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Prostate Cancer
Keywords: prostate
cancer
radiation
proton
chemotherapy
high risk
Lead sponsor: Proton Collaborative Group
Sponsor class: NETWORK
First posted: 2012-05-22
Enrollment: 2
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the effects on prostate cancer using radiation therapy with or without chemotherapy.

Detailed description: The recommended treatment for a high risk prostate cancer consists of a combination of radiation therapy and androgen suppression for 2-3 years. Recent studies have shown a survival advantage for chemotherapy for prostate cancer. Chemotherapy has already been successfully integrated in the treatment of other cancer types and is our belief that chemotherapy will prove to be beneficial for patients with high risk prostate cancer. However, a clinical study is necessary to compare the results good or bad of chemotherapy with radiation therapy.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed prostate adenocarcinoma (within 365 days of randomization.
* High-risk for recurrence as determined by evidence of at least one of the following: Gleason score 8-10, PSA \> 20, T state T3.
* Histological evaluation of prostate biopsy with assignment of a Gleason score to the biopsy material: Gleason score must be in the range 2-10. \> 6 cores are strongly recommended.
* Clinical stages T1a- T3 N0 M0 as staged by the treating investigator. (AJCC Criteria 7th Ed.-appendix III).
* PSA values \< = 50 ng/ml within 90 days prior to randomization. Must be completed prior to biopsy or at least 21 days after prostate biopsy.
* Absolute Neutrophil Count (ANC) \> = 1,800 cells/mm³ within 90 days prior to randomization.
* Platelets \> = 100,000 cells/mm³ within 90 days prior to randomization.
* Hemoglobin \> 10 g/dl within 90 days prior to randomization.
* ALT, AST, and total bilirubin within 1.5 X institutional upper normal limits within 90 days prior to randomization.
* ECOG status 0-1 (appendix II) documented within 90 days of randomization.
* Patient must sign study specific informed consent prior to randomization. Note: consent for legally authorized representative is not permitted.
* Completed all requirements listed in section 4.0 within the specified time frames.
* Able to start treatment within 56 days of randomization.
* At least 18 years old and less than or equal to 75 years of age.
* Men of child-producing potential must be willing to consent to use effective contraception while on treatment and for at least 3 months afterwards.
* Medical oncology consultation prior to randomization and medically approved for chemotherapy treatment per protocol.

Exclusion Criteria:

* Evidence of distant metastasis.
* Pelvic lymph nodes \> 1.5 cm in greatest dimension unless the enlarged lymph node is biopsied and negative.
* Prior prostate cancer surgery including but not limited to prostatectomy, hyperthermia and cryosurgery.
* Prior pelvic radiation for their prostate cancer.
* Prior androgen deprivation.
* Severe, active co-morbidity, defined as follows:
* Active rectal diverticulitis, Crohn's disease affecting the rectum or ulcerative colitis. (Non-active diverticulitis and Crohn's disease not affecting the rectum are allowed).
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months.
* Myocardial infarction within the last 6 months.
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization.
* Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
* Prior allergic reaction to the drugs involved in this protocol.
* Existing peripheral neuropathy \> = grade 2.
* Prior systemic chemotherapy for prostate cancer.
* History of proximal urethral stricture requiring dilatation.
* Major medical, addictive or psychiatric illness which in the investigator's opinion, will prevent the consent process, completion of the treatment and/or interfere with follow-up.
* Evidence of any other cancer within the past 5 years and \< 50% probability of a 5 year survival. (Prior or concurrent diagnosis of basal cell or non-invasive squamous cell cancer of the skin is allowed.)

Primary outcomes:
measure: Phase 2 - Assessment of Number of Freedom From Failure Events in the Chemotherapy Arm
timeFrame: No failures were reported at the time of study termination (22 months). This outcome was originally written to assess failure at 2 years. However, that end point was not reached.
measure: Phase 2 - Assessment of Number of Freedom From Failure Event Comparing Chemotherapy Arm to Standard Treatment Arm
timeFrame: at 5 years
measure: Phase 2 - Cumulative Number of Incidences of Grade 3 or Higher Adverse Events.
timeFrame: 2 years
measure: Phase 3 - Assessment of the Number of Freedom From Failure (FFF) Events Comparing the Chemotherapy Arm to the Standard Treatment Arm.
timeFrame: at 5 years
Secondary outcomes:
measure: Assessment of Number of Grade 2 or Higher Genitourinary (GU) and Gastrointestinal (GI) Adverse Events
timeFrame: at 6 months
measure: Assessment of Number of GI and GU Adverse Events
timeFrame: at 3 years
measure: Assessment of Total Number of Local/Distant Failures
timeFrame: at time of study closure (22 months)
measure: Assessment of Impotence by Summation of Relative Scores for Sexual Function From the EPIC Quality of Life Instrument.
timeFrame: Up to 10 years
measure: Assessment of Total Number of Salvage Androgen Deprivation Use With Comparison of Arms.
timeFrame: At study closure (22 months)
measure: Assessment of Total Number of Survival Events With Comparison of Group Arms
timeFrame: at study closure (22 months)
measure: Assessment of Total Number of Biochemical Failure Events
timeFrame: at study closure (22 months)
measure: Assessment of Quality of Life - Summation of Relative Scores From the EPIC Instrument.
timeFrame: Up to 10 years
Other outcomes:
Locations:
city: Warrenville
country: United States
facility: CDH Proton Center
state: Illinois
city: Oklahoma City
country: United States
facility: Procure Proton Therapy Center
state: Oklahoma
city: Hampton
country: United States
facility: Hampton University Proton Therapy Institute
state: Virginia
Study officials:
affiliation: Proton Collaborative Group
name: Carlos Vargas, MD
role: STUDY_CHAIR
References:
citation: Guttilla A, Bortolus R, Giannarini G, Ghadjar P, Zattoni F, Gnech M, Palumbo V, Valent F, Garbeglio A, Zattoni F. Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial. Radiat Oncol. 2014 Jan 14;9:24. doi: 10.1186/1748-717X-9-24.