Clinical Trial Comparing 3-D RT vs. IMRT in Post- Prostatectomy Prostate Cancer Patients

NCT02678520 | Withdrawn Phase 2 DMC

• 1 other identifier: 2015-IIT-RT-IMRT
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Compare the incidence of acute rectal, bladder and other acute toxicities between 3-D Conformal Radiation Therapy (RT/CRT) and Intensity Modulated Radiation Therapy (IMRT) in Post-Prostatectomy Prostate Cancer Patients treated with post-operative radiation therapy

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Post Operative; Radiation; Prostatectomy; 3-D CRT; IMRT; RT; CRT; Conformal Radiation Therapy; Intensity Modulated Radiation Therapy; Hormone; Surgery; Hormonal Therapy

Outcome Measures

Primary Outcomes (5)

• Acute rectal, bladder and other toxicity rates - For participants 1 through 10 in each treatment arm

  Acute rectal, bladder and other toxicity rates will be estimated and 95% exact binomial confidence intervals will be calculated. Toxicity will be measured via analysis of patient adverse events (physiological parameter). Adverse events will be scored using NCI Common Toxicity Criteria for Adverse Events v 4.0.3 (June 14, 2010). A two-sample binomial test will be used. This time point is an interim toxicity monitoring event designed to protect against the unlikely event of significantly more grade 2 or higher toxicities in one treatment vs. the other. If at any point, after the first 10 patients in each arm, the grade 2 or higher acute toxicity rate in either arm is more than double the grade 2 or higher acute toxicity rate in the other treatment arm, enrollment will be suspended and review of safety profiles conducted. The PI and Data Safety Monitoring Committee will then either modify the protocol or close the study to accrual.

  Toxicity measured weekly starting at pre-treatment eval. and ending at end of treatment of participant 10 in both arms (Btwn approx. 7 to 11 wks per participant/through end of study; approx. 2 years)

• Acute rectal, bladder and other toxicity rates - For all 100 study participants

  After safety issues, if any, have been resolved and study continued, the TOTAL of ALL 100 subjects (50 in each treatment arm) will be measured thus: Acute rectal, bladder and other toxicity rates will be estimated and 95% exact binomial confidence intervals will be calculated. To compare these rates between 3-D CRT and IMRT treatment arms, a two-sample binomial test will be used. Toxicity will be measured via analysis of patient adverse events (physiological parameter). Adverse events will be scored using NCI Common Toxicity Criteria for Adverse Events v 4.0.3 (June 14, 2010).

  Toxicity measured weekly starting at pre-treatment eval. and ending at end of treatment of participant 100 (Btwn approx. 7 to 11 wks per participant/through end of study; approx. 2 years)

• Dose Volume Histogram (DVH) dose quantification and comparison

  To quantify and compare the dose volume histogram (DVH) doses (e.g., Vmean, Vmedian, V25, V50, V75) to the surrounding critical organs (i.e., rectum and bladder) between 3-D CRT and IMRT, a two-sample t-test will be used.

  DVH assessed at end of radiation therapy for each participant (Btwn approx. 7 to 11 wks for each participant) Overall DVH values compared at end of study-approx. 2 years)

• Quality of Life measure and comparison - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ C-30)

  To measure and compare participants' quality of life, overall scores will be obtained from participants via the EORTC QLQ C-30 survey instrument. This tool is used for each participant's measure of their own quality of life with this cancer. A two-sample t-test will then be used to make the comparison between treatment arms.

  EORTC QLQ C-30 will be assessed 2 times during each participant's study enrollment: at pre-treatment eval. (Wk 0), + after completion of radiation therapy (Betwn approx. wks 7 to 11) Overall scores will be compared at end of study - approx. 2 years

• Quality of Life measure and comparison - Expanded Prostate Cancer Index Composite 26 (EPIC-26)

  To measure and compare participants' quality of life, overall scores will be obtained from participants via the EPIC-26 survey instrument. This tool is used for each participant's measure of their own quality of life with this cancer. A two-sample t-test will then be used to make the comparison between treatment arms.

  EPIC-26 will be assessed 2 times during each participant's study enrollment: at pre-treatment eval. (Wk 0), + after completion of radiation therapy (Betwn approx. wks 7 to 11) Overall scores will be compared at end of study - approx. 2 years

Study Arms (2)

3-D conformal radiation therapy

EXPERIMENTAL

Intervention: Radiation therapy delivered to a total dose of 6600 centigray (cGy) at 200 cGy/fraction (fx) once daily using a 3-D conformal radiation technique (3-D CRT). The volume of radiation will encompass the prostatic fossa / surgical bed including any suspected regions of microscopic disease such as positive margins, extracapsular extension and/or seminal vesicle involvement. Hormonal therapy will be required for patients with "high risk" disease (both the adjuvant and salvage groups). For patients with "low risk" disease, hormonal therapy will be as per standard of care. Hormonal therapy will typically begin 2 months prior to radiation and continue for a total of 6 months. Hormonal therapy regimen will consist of Casodex (50 mg/day po for 6 months) and Zoladex (10.8 mg sc once every 3 months x 2 injections) or Lupron (22.5 mg im once every 3 months x 2 injections) to start on day 1 once the subject has been enrolled to the clinical trial.

Radiation: 3-D Conformal Radiation Therapy; Drug: Casodex, Zoladex , Lupron

Intensity modulated radiation therapy

ACTIVE COMPARATOR

Intervention: Radiation therapy delivered to a total dose of 6600 centigray (cGy) at 200 cGy/fraction (fx) once daily using intensity modulated radiation therapy (IMRT). The volume of radiation will encompass the prostatic fossa / surgical bed including any suspected regions of microscopic disease such as positive margins, extracapsular extension and/or seminal vesicle involvement. Hormonal therapy will be required for patients with "high risk" disease (both the adjuvant and salvage groups). For patients with "low risk" disease, hormonal therapy will be as per standard of care. Hormonal therapy will typically begin 2 months prior to radiation and continue for a total of 6 months. Hormonal therapy regimen will consist of Casodex (50 mg/day po for 6 months) and Zoladex (10.8 mg sc once every 3 months x 2 injections) or Lupron (22.5 mg im once every 3 months x 2 injections) to start on day 1 once the subject has been enrolled to the clinical trial.

Radiation: Intensity Modulated Radiation Therapy; Drug: Casodex, Zoladex , Lupron

Interventions

3-D Conformal Radiation Therapy RADIATION

Radiation delivered after surgery to remove the prostate, using 3-D Conformal Radiation Therapy. Radiation will be delivered to prostatic fossa / surgical bed including any suspected regions of microscopic disease such as positive margins, extracapsular extension and/or seminal vesicle involvement. The total dose of radiation will be 6600 centigray (cGy) at 200 cGy/fraction (fx) given once daily .

Also known as: 3-D CRT

3-D conformal radiation therapy

Intensity Modulated Radiation Therapy RADIATION

Radiation delivered after surgery to remove the prostate, using Intensity Modulated Radiation Therapy. Radiation will be delivered to prostatic fossa / surgical bed including any suspected regions of microscopic disease such as positive margins, extracapsular extension and/or seminal vesicle involvement. The total dose of radiation will be 6600 centigray (cGy) at 200 cGy/fraction (fx) given once daily .

Also known as: IMRT

Intensity modulated radiation therapy

Casodex, Zoladex , Lupron DRUG

Hormonal Therapy (6 Months): Required for "High Risk" Groups, and as per Standard of Care for "Low Risk" Groups. Hormonal therapy protocol regimen for the high risk "adjuvant" and "salvage" groups will consist of Casodex (50 mg/day po for 6 months) and Zoladex (10.8 mg subcutaneously once every 3 months x 2) or Lupron (22.5 mg given intramuscularly once every 3 months x 2 injections or 7.5 mg IM q once monthly x 6) to start on day 1 of the clinical trial. Hormonal therapy will typically begin 2 months prior to radiation and continue for a total of 6 months.

Also known as: Hormone Therapy

3-D conformal radiation therapy; Intensity modulated radiation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented adenocarcinoma of the prostate.
• Status post radical prostatectomy with sampling of the pelvic lymph nodes with histologically confirmed adenocarcinoma of the prostate, with the patients falling into either the "adjuvant low or high risk groups" or the "salvage low or high risk groups" as indicated below. In those cases where patients undergo a prostatectomy without any sampling of the pelvic lymph nodes, patients will be also considered eligible if they are found to have a negative pelvic CT or MRI scan which shows no evidence of lymphatic nodal metastases after the prostatectomy.
• "Adjuvant High Risk Group" are those patients with an undetectable or persistent/decreasing PSA levels (before starting therapy) who MUST be able to start radiation therapy treatments within 6 months of radical prostatectomy with at least ONE of the 3 disease features:
• Pathologic T2N0 (with no clinical evidence of metastases) and Gleason Score ≥ 8
• Pathologic T3aN0 (with no clinical evidence of metastases) with Extra-Capsular Extension and Gleason Score ≥ 8
• Pathologic T3bN0 (with no clinical evidence of metastases) with any Gleason Score
• "Salvage High Risk Group" are those patients who experience a PSA failure (defined as at least 1 detectable PSA level \> 0.2 ng/ml or at least 2 consecutive increases in PSA levels over baseline which are at least 1 month apart after radical prostatectomy) with at least ONE of the 4 following features:
• Pathologic T3bN0 disease (with no clinical evidence of metastases),
• Pathologic T2-3aN0 disease (with no clinical evidence of metastases) with Gleason Score ≥ 8,
• Pathologic T2-3aN0 disease (with no clinical evidence of metastases) with PSA Doubling Time ≤ 10 months,
• Pathologic T2-3aN0disease (with no clinical evidence of metastases) with Pre-RT PSA level ≥ 1.0 ng/ml
• "Adjuvant Low Risk Group" are those patients with an undetectable or persistent/decreasing PSA levels (before starting therapy) who MUST be able to start radiation therapy treatments within 6 months of radical prostatectomy with at least ONE of the 2 disease features:
• Pathologic T2N0 (with no clinical evidence of metastases), Gleason Score ≤ 7, with positive margins
• Pathologic T3aN0 (with no clinical evidence of metastases) with Extra-Capsular Extension, Gleason Score ≤ 7, with or without positive margins
• "Salvage Low Risk Group" are those patients who experience a PSA failure (defined as at least 1 detectable PSA level \> 0.2 ng/ml or at least 2 consecutive increases in PSA levels over baseline which are at least 1 month apart after radical prostatectomy) with the following feature: - Pathologic T2-3aN0 disease (with no clinical evidence of metastases) with Gleason Score ≤7, with or without positive margins

You may not qualify if:

• Patients who have received prior pelvic irradiation are not eligible.
• Any coexisting medical condition precluding full compliance with the study.
• Patients with active infections or known infection with HIV. Testing for HIV status will not be required.
• Psychological, familiar, sociological or geographical conditions which would not permit compliance with the study protocol.

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

The University of Kansas Cancer Center (KUCC)

Fairway, Kansas, 66205, United States

Location

Related Publications (3)

• Pilepich MV, Winter K, John MJ, Mesic JB, Sause W, Rubin P, Lawton C, Machtay M, Grignon D. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1243-52. doi: 10.1016/s0360-3016(01)01579-6.

  PMID: 11483335 BACKGROUND

• D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA. 2004 Aug 18;292(7):821-7. doi: 10.1001/jama.292.7.821.

  PMID: 15315996 BACKGROUND

• Denham JW, Steigler A, Lamb DS, Joseph D, Mameghan H, Turner S, Matthews J, Franklin I, Atkinson C, North J, Poulsen M, Christie D, Spry NA, Tai KH, Wynne C, Duchesne G, Kovacev O, D'Este C; Trans-Tasman Radiation Oncology Group. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol. 2005 Nov;6(11):841-50. doi: 10.1016/S1470-2045(05)70348-X.

  PMID: 16257791 BACKGROUND

Related Links

• American Cancer Society, Cancer Facts and Figures, 2014, p. 4

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; bicalutamide; Goserelin; Leuprolide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Parvesh Kumar, MD

  University of Kansas Medical Center - Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: February 9, 2016
• Study Start: December 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: July 22, 2016

Record last verified: 2016-07

Locations

US (1)