Clinical Trials of Adjuvant Androgen Deprivation in Localized Prostate Cancer

Prostate Adenocarcinoma Clinical Trial

— AADLPC  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02175212
• Other study ID #: DART01/05
• Status: Completed
• Phase: Phase 3
• Start date: November 2005
• Est. completion date: September 24, 2020

Study information

• Verified date: November 2020
• Source: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 362
• Est. completion date: September 24, 2020
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• 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
• 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

Radiation:
• Short term androgen deprivation
Minimum dose of 76 Gy (range 76-82 Gy)
• Long term androgen deprivation
Minimum dose of 76 Gy (range 76-82 Gy)

Locations

Country	Name	City	State
Spain	Hospital Universitario de la Princesa	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Country where clinical trial is conducted

Spain, 

References & Publications (17)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Zapatero A, Valcárcel F, Calvo FA, Algás R, Béjar A, Maldonado J, Villá S. Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvan — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biochemical Disease Free Survival: Estimated Percentage of Participants With Biochemical Disease-free Survival at 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).	5 years
Secondary	Metastasis Free Survival: Estimated Percentage of Participants With Metastasis-free Survival at 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).	5 years
Secondary	Overall Survival: Estimated Percentage of Participants Alive at 5 Years	Overall Survival: defined as the time that elapses from the patient enters the study until the patient dies from any cause.	5 years
Secondary	Cause-specific Survival	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	5 years
Secondary	Late Toxicity	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	5 years