Clinical Trials of Adjuvant Androgen Deprivation in Localized Prostate Cancer

NCT ID: NCT02175212

Last Updated: 2020-11-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

362 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-11-30

Study Completion Date

2020-09-24

Brief Summary

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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

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Conditions

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Prostate Adenocarcinoma

Keywords

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Patients with prostate adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Long term androgen deprivation

Intervention Type DRUG

* 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

Long term androgen deprivation

Intervention Type RADIATION

Minimum dose of 76 Gy (range 76-82 Gy)

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

Group Type ACTIVE_COMPARATOR

Short term androgen deprivation

Intervention Type DRUG

* 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

Short term androgen deprivation

Intervention Type RADIATION

Minimum dose of 76 Gy (range 76-82 Gy)

Interventions

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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

Intervention Type 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

Intervention Type DRUG

Short term androgen deprivation

Minimum dose of 76 Gy (range 76-82 Gy)

Intervention Type RADIATION

Long term androgen deprivation

Minimum dose of 76 Gy (range 76-82 Gy)

Intervention Type RADIATION

Other Intervention Names

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Neoadjuvant and concomitant Neoadjuvant, concomitant and adjuvant

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Almudena Zapatero, MD PhD, IP

Role: PRINCIPAL_INVESTIGATOR

Grupo de Investigación Clínica en Oncología Radioterapia

Locations

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Hospital Universitario de la Princesa

Madrid, , Spain

Site Status

Countries

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Spain

References

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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.

Reference Type BACKGROUND
PMID: 12128107 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9635694 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11490237 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11728678 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12243818 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14571409 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9276374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9123741 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12126818 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11483335 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11240234 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9598512 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3133327 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15817329 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12902891 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12957248 (View on PubMed)

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.

Reference Type RESULT
PMID: 16170164 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35427469 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27598804 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25702876 (View on PubMed)

Other Identifiers

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DART01/05

Identifier Type: -

Identifier Source: org_study_id