External Beam Radiation With or Without Chemotherapy to Treat High Risk Prostate Cancer

Phase 2/3 Study of Dose-escalated External Beam Radiation Therapy With or Without Chemotherapy for High Risk Adenocarcinoma of the Prostate

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

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Luteinizing hormone-releasing hormone (LHRH); Other: Conformal Radiation Therapy (RT); Drug: Docetaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Warrenville, Illinois, United States, 60555
      • CDH Proton Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73142
      • ProCure Proton Therapy Center
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Hampton University Proton Therapy Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Radiation + 24mo luteinizing hormone-releasing hormone (LHRH); Conformal RT 79.2 Gy(RBE) total dose + 24 months LHRH agonist (androgen suppression).	Drug: Luteinizing hormone-releasing hormone (LHRH); Androgen suppression therapy using luteinizing hormone-releasing hormone (LHRH) agonists such as leuprolide, goserelin, buserelin, triptorelin.; Other Names: -Androgen Suppression; -Androgen Deprivation; -Zoladex; -Lupron; -Eligard; -Viadur; Other: Conformal Radiation Therapy (RT); 1.8 Gy(RBE) (or Gy for IMRT) per fraction,five fractions per week for a total dose of 79.2 Gy (RBE) (or Gy).; Other Names: Intensity-modulated Radiation Therapy (IMRT); Proton Therapy; Particle Therapy
Experimental: Radiation + Chemo + 6mo luteinizing hormone-releasing hormone; Conformal RT 79.2 Gy(RBE) total dose + Chemotherapy: Docetaxel 20mg/m2 x every 7 days x 8 weeks followed by 6 months LHRH (androgen suppression).	Drug: Luteinizing hormone-releasing hormone (LHRH); Androgen suppression therapy using luteinizing hormone-releasing hormone (LHRH) agonists such as leuprolide, goserelin, buserelin, triptorelin.; Other Names: -Androgen Suppression; -Androgen Deprivation; -Zoladex; -Lupron; -Eligard; -Viadur; Other: Conformal Radiation Therapy (RT); 1.8 Gy(RBE) (or Gy for IMRT) per fraction,five fractions per week for a total dose of 79.2 Gy (RBE) (or Gy).; Other Names: Intensity-modulated Radiation Therapy (IMRT); Proton Therapy; Particle Therapy; Drug: Docetaxel; Docetaxel 20mg/m2 IV every 7 days x 8 weeks.; Other Names: -taxotere; -docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2 - Assessment of Number of Freedom From Failure Events in the Chemotherapy Arm	Measurement of Freedom from Failure i.e. the first occurence of clinical failure (local recurrence, regional recurrence, or distant metastasis), biochemical failure by the Phoenix definition (Prostate Specific Antigen [PSA] > = 2 ng/ml over the nadir PSA discounting bounces per the investigators discretion), or the start of salvage therapy including androgen deprivation. This study was terminated prior to the time frame of 2 years being reached. Therefore, this outcome was assessed at time of study closure (22 months).	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.
Phase 2 - Assessment of Number of Freedom From Failure Event Comparing Chemotherapy Arm to Standard Treatment Arm	This endpoint will be examined if decision is made to not move forward with phase 3 study. This study was terminated prior to a decision being made about moving on to a phase 3 study. Therefore, this outcome was not assessed.	at 5 years
Phase 2 - Cumulative Number of Incidences of Grade 3 or Higher Adverse Events.	Assessment will be performed using CTCAE v4 criteria. This study was terminated prior to the time frame of 2 years being reached. Therefore, this outcome was assessed at time of study closure (22 months).	2 years
Phase 3 - Assessment of the Number of Freedom From Failure (FFF) Events Comparing the Chemotherapy Arm to the Standard Treatment Arm.	The events for FFF will be the first occurence of clinical failure (local recurrence, regional recurrence, or distant metastasis), biochemical failure by the Phoenix definition (PSA > = ng/ml over the nadir PSA discounting bounces per the investigators discretion), or the start of salvage androgen deprivation. This study was terminated prior to a decision being made about moving on to a phase 3 study. Therefore, this outcome was not assessed.	at 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Number of Grade 2 or Higher Genitourinary (GU) and Gastrointestinal (GI) Adverse Events	Assessment will be performed using CTCAE v 4 criteria.	at 6 months
Assessment of Number of GI and GU Adverse Events	Descriptive measurements of frequency will be compiled. This study was terminated prior to the time frame of 3 years being reached. Therefore, this outcome was not assessed. Data were collected on toxicities up until study closure at 22 months. However, this timepoint was not indicated as a secondary objective in the protocol. Therefore, data was not analyzed at time of study closure.	at 3 years
Assessment of Total Number of Local/Distant Failures	The total number of local/distant failures will be assessed.	at time of study closure (22 months)
Assessment of Impotence by Summation of Relative Scores for Sexual Function From the EPIC Quality of Life Instrument.	unable to assess due to lack of data	Up to 10 years
Assessment of Total Number of Salvage Androgen Deprivation Use With Comparison of Arms.	The total number of subjects with salvage androgen deprivation use will be assessed.	At study closure (22 months)
Assessment of Total Number of Survival Events With Comparison of Group Arms	The number of deaths in both arms will be assessed.	at study closure (22 months)
Assessment of Total Number of Biochemical Failure Events	The number of biochemical failure events will be assessed on both arms.	at study closure (22 months)
Assessment of Quality of Life - Summation of Relative Scores From the EPIC Instrument.	unable to assess due to lack of data	Up to 10 years

Collaborators and Investigators

• Sponsor: Proton Collaborative Group
• Investigators: Study Chair: Carlos Vargas, MD, Proton Collaborative Group

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: May 18, 2012
• First Submitted That Met QC Criteria: May 18, 2012
• First Posted (Estimate): May 22, 2012

Study Record Updates

• Last Update Posted (Estimate): March 14, 2016
• Last Update Submitted That Met QC Criteria: February 11, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: chemotherapy; cancer; radiation; prostate; high risk; proton
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Estrogens; Micronutrients; Vitamins; Antioxidants; Anabolic Agents; Docetaxel; Hormones; Ascorbic Acid; Androgens; Prolactin Release-Inhibiting Factors; Methyltestosterone; Estrogens, Conjugated (USP)
• Other Study ID Numbers: GU004-11