Clinical Trials of Adjuvant Androgen Deprivation in Localized Prostate Cancer (AADLPC)

• ClinicalTrials.gov Identifier: NCT02175212
• Recruitment Status: Completed
• First Posted: June 26, 2014
• Results First Posted: November 4, 2016
• Last Update Posted: November 20, 2020
• Sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Information provided by (Responsible Party): Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Tracking Information

• First Submitted Date: June 23, 2014
• First Posted Date: June 26, 2014
• Results First Submitted Date: May 4, 2016
• Results First Posted Date: November 4, 2016
• Last Update Posted Date: November 20, 2020
• Study Start Date: November 2005
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 16, 2016)

Biochemical Disease Free Survival: Estimated Percentage of Participants With Biochemical Disease-free Survival at 5 Years [ Time Frame: 5 years ]

Biochemical relapse was defined as the time from inclusion in the study (randomization) until the patient meets criteria for Biochemical failure (Phoenix criteria: PSA nadir plus 2 ng/ml).

• Original Primary Outcome Measures (submitted: June 25, 2014): Biochemical relapse was defined as the time from inclusion in the study (randomization) until the patient meets criteria for Biochemistry (Phoenix criteria: PSA nadir plus 2 ng/ml). [ Time Frame: 5 years ]

Current Secondary Outcome Measures (submitted: September 16, 2016)

• Metastasis Free Survival: Estimated Percentage of Participants With Metastasis-free Survival at 5 Years [ Time Frame: 5 years ]
  Metastasis free survival: defined as the time from inclusion in the study (randomization) until the appearance of distant metastases: a positive result in any of the tests performed (scintigraphy, chest radiography, thorax, abdominal and pelvic CT and MRI).
• Overall Survival: Estimated Percentage of Participants Alive at 5 Years [ Time Frame: 5 years ]
  Overall Survival: defined as the time that elapses from the patient enters the study until the patient dies from any cause.
• Cause-specific Survival [ Time Frame: 5 years ]
  Cause-specific survival included all deaths from prostate cancer or treatment complications, and deaths from unknown causes in patients with either active cancer or a previously documented relapse
• Late Toxicity [ Time Frame: 5 years ]
  Defined as the maximal rectal, urinary and cardiovascular (CV) toxicity per patient more than 90 days after completion of RT. Scoring scales used were the radiation morbidity scoring criteria of the European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group (EORTC/RTOG) and the Common Terminology Criteria for Adverse Events (CTCAEs) v 3.0 for the remained toxicity. CV events were defined according to the World Health Organization criteria

Original Secondary Outcome Measures (submitted: June 25, 2014)

Metastasis free survival. [ Time Frame: 3 and 5 years ]

Metastasis free survival: defined as the time from inclusion in the study (randomization) until the appearance of distant metastases: a positive result in any of the tests performed (scintigraphy, chest radiography, thorax, abdominal and pelvic CT and MRI).

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: June 25, 2014)

Overall Survival [ Time Frame: 3 and 5 years ]

Overall Survival: defined as the time that elapses from the patient enters the study until the patient dies from any cause.

Descriptive Information

• Brief Title: Clinical Trials of Adjuvant Androgen Deprivation in Localized Prostate Cancer
• Official Title: Phase III Multicenter Randomized Trial of Adjuvant Androgen Deprivation in Combination With Three-dimensional Conformal Radiotherapy Doses in High and Intermediate Risk Localized Prostate Cancer.
• Brief Summary: The present study is a phase III randomized and multicentric trial evaluating the potential additional impact effect of two years adjuvant androgen deprivation when combined with neoadjuvant (4 months) and high-dose (76 Gy) conformal radiotherapy in moderate high-risk prostate cancer patients. Stratification will be performed by prognostic factors and by participating institution.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Adenocarcinoma

Intervention

• Drug: Short term androgen deprivation
  • Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months)
  • Bicalutamide 50 mg tablet every day for 2 months
  Other Name: Neoadjuvant and concomitant
• Drug: Long term androgen deprivation
  • Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months)
  • Bicalutamide 50 mg tablet every day for 2 months
  • Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy
  Other Name: Neoadjuvant, concomitant and adjuvant
• Radiation: Short term androgen deprivation
  Minimum dose of 76 Gy (range 76-82 Gy)
• Radiation: Long term androgen deprivation
  Minimum dose of 76 Gy (range 76-82 Gy)

Study Arms

• Experimental: Long term androgen deprivation
  • Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months)
  • Bicalutamide 50 mg tablet every day for 2 months
  • High dose conformal radiotherapy
  • Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy
  Interventions:

  • Drug: Long term androgen deprivation
  • Radiation: Long term androgen deprivation
• Active Comparator: Short term androgen deprivation
  • Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months)
  • Bicalutamide 50 mg tablet every day for 2 months
  • High dose conformal radiotherapy
  Interventions:

  • Drug: Short term androgen deprivation
  • Radiation: Short term androgen deprivation

Publications *

• Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, von Eschenbach AC, Kuban DA, Rosen I. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1097-105. doi: 10.1016/s0360-3016(02)02829-8.
• Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Venkatramen ES, Reuter VE, Fair WR, Ling CC, Fuks Z. Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys. 1998 Jun 1;41(3):491-500. doi: 10.1016/s0360-3016(98)00091-1.
• Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC, Reuter VE, Venkatraman ES, Leibel SA. High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol. 2001 Sep;166(3):876-81. Erratum In: J Urol 2001 Nov;166(5):1839.
• Vicini FA, Abner A, Baglan KL, Kestin LL, Martinez AA. Defining a dose-response relationship with radiotherapy for prostate cancer: is more really better? Int J Radiat Oncol Biol Phys. 2001 Dec 1;51(5):1200-8. doi: 10.1016/s0360-3016(01)01799-0.
• Hanks GE, Hanlon AL, Epstein B, Horwitz EM. Dose response in prostate cancer with 8-12 years' follow-up. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):427-35. doi: 10.1016/s0360-3016(02)02954-1.
• Leibel SA, Fuks Z, Zelefsky MJ, Hunt M, Burman CM, Mageras GS, Chui CS, Jackson A, Amols HI, Ling CC. Technological advances in external-beam radiation therapy for the treatment of localized prostate cancer. Semin Oncol. 2003 Oct;30(5):596-615. doi: 10.1016/s0093-7754(03)00354-3.
• Joon DL, Hasegawa M, Sikes C, Khoo VS, Terry NH, Zagars GK, Meistrich ML, Pollack A. Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation. Int J Radiat Oncol Biol Phys. 1997 Jul 15;38(5):1071-7. doi: 10.1016/s0360-3016(97)00303-9.
• Zietman AL, Prince EA, Nakfoor BM, Shipley WU. Neoadjuvant androgen suppression with radiation in the management of locally advanced adenocarcinoma of the prostate: experimental and clinical results. Urology. 1997 Mar;49(3A Suppl):74-83. doi: 10.1016/s0090-4295(97)00173-8.
• Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002 Jul 13;360(9327):103-6. doi: 10.1016/s0140-6736(02)09408-4.
• 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.
• Lawton CA, Winter K, Murray K, Machtay M, Mesic JB, Hanks GE, Coughlin CT, Pilepich MV. Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001 Mar 15;49(4):937-46. doi: 10.1016/s0360-3016(00)01516-9.
• Granfors T, Modig H, Damber JE, Tomic R. Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study. J Urol. 1998 Jun;159(6):2030-4. doi: 10.1016/S0022-5347(01)63235-X.
• Zagars GK, Johnson DE, von Eschenbach AC, Hussey DH. Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long-term results of a prospective randomized study. Int J Radiat Oncol Biol Phys. 1988 Jun;14(6):1085-91. doi: 10.1016/0360-3016(88)90383-5.
• Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B, Hug EB, Asbell SO, Grignon D. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1285-90. doi: 10.1016/j.ijrobp.2004.08.047.
• Jani AB, Basu A, Abdalla I, Connell PP, Krauz L, Vijayakumar S. Impact of hormone therapy when combined with external beam radiotherapy for early-stage, intermediate-, or high-risk prostate cancer. Am J Clin Oncol. 2003 Aug;26(4):382-5. doi: 10.1097/01.COC.0000026483.80660.94.
• Nguyen KH, Horwitz EM, Hanlon AL, Uzzo RG, Pollack A. Does short-term androgen deprivation substitute for radiation dose in the treatment of high-risk prostate cancer? Int J Radiat Oncol Biol Phys. 2003 Oct 1;57(2):377-83. doi: 10.1016/s0360-3016(03)00573-x.
• Zapatero A, Valcarcel F, Calvo FA, Algas R, Bejar A, Maldonado J, Villa S. Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study. J Clin Oncol. 2005 Sep 20;23(27):6561-8. doi: 10.1200/JCO.2005.09.662.
• Zapatero A, Guerrero A, Maldonado X, Alvarez A, San-Segundo CG, Rodriguez MAC, Sole JM, Olive AP, Casas F, Boladeras A, de Vidales CM, de la Torre MLV, Vara S, Sanz JL, Calvo FA. High-dose radiotherapy and risk-adapted androgen deprivation in localised prostate cancer (DART 01/05): 10-year results of a phase 3 randomised, controlled trial. Lancet Oncol. 2022 May;23(5):671-681. doi: 10.1016/S1470-2045(22)00190-5. Epub 2022 Apr 12.
• Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez-San Segundo C, Cabeza Rodriguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, Martin de Vidales C, Vazquez de la Torre ML, Calvo FA. Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial. Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):341-348. doi: 10.1016/j.ijrobp.2016.06.2445. Epub 2016 Jun 22.
• Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodriguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villa S, Perez de la Haza A, Calvo FA. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Mar;16(3):320-7. doi: 10.1016/S1470-2045(15)70045-8. Epub 2015 Feb 19. Erratum In: Lancet Oncol. 2015 Jun;16(6):e262.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 16, 2016): 362
• Original Actual Enrollment (submitted: June 25, 2014): 358
• Actual Study Completion Date: September 24, 2020
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histological proven adenocarcinoma of the prostate
• Stage: cT1c-3b N0M0 according to American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM)
• Prostatic Specific Antigen (PSA)<100 ng/ml
• Intermediate (T1-T2 with Gleason Score [GS] 7 and/or PSA 10-20)
• High risk (T3 and/or GS 8-10 and/or PSA > 20)
• Karnofsky Index (KI) performance status ≥70%
• Written informed consent

Exclusion Criteria:

• T4 N1 M1,
• Previous surgical treatment (prostatectomy or cryosurgery)
• Neoadjuvant hormonal treatment > 3 months.
• History of pelvic radiotherapy (RT)
• Contraindications for radiotherapy
• Concomitant use of chemotherapy
• Serious psychiatric or medical condition
• Current synchronic malignancies

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT02175212
• Other Study ID Numbers: DART01/05
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Original Responsible Party: Same as current
• Current Study Sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Almudena Zapatero, MD PhD, IP; Grupo de Investigación Clínica en Oncología Radioterapia

• PRS Account: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Verification Date: November 2020