Clinical Trials of Adjuvant Androgen Deprivation in Localized Prostate Cancer

NCT02175212 | Completed Phase 3 Results

• 1 other identifier: DART01/05
• Study Type: interventional
• Target: 362
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Adenocarcinoma

Keywords

Patients with prostate adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Metastasis Free Survival: Estimated Percentage of Participants With Metastasis-free Survival at 5 Years

  5 years

• Overall Survival: Estimated Percentage of Participants Alive at 5 Years

  5 years

• Cause-specific Survival

  5 years

• Late Toxicity

  5 years

Study Arms (2)

Long term androgen deprivation

EXPERIMENTAL

* 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

Drug: Long term androgen deprivation; Radiation: Long term androgen deprivation

Short term androgen deprivation

ACTIVE COMPARATOR

* 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

Drug: Short term androgen deprivation; Radiation: Short term androgen deprivation

Interventions

Short term androgen deprivation 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

Also known as: Neoadjuvant and concomitant

Short term androgen deprivation

Long term androgen deprivation 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

Also known as: Neoadjuvant, concomitant and adjuvant

Long term androgen deprivation

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa: lead

Study Sites (1)

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Related Publications (20)

• 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.

  PMID: 12128107 BACKGROUND

• 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.

  PMID: 9635694 BACKGROUND

• 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.

  PMID: 11490237 BACKGROUND

• 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.

  PMID: 11728678 BACKGROUND

• 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.

  PMID: 12243818 BACKGROUND

• 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.

  PMID: 14571409 BACKGROUND

• 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.

  PMID: 9276374 BACKGROUND

• 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.

  PMID: 9123741 BACKGROUND

• 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.

  PMID: 12126818 BACKGROUND

• 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

• 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.

  PMID: 11240234 BACKGROUND

• 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.

  PMID: 9598512 BACKGROUND

• 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.

  PMID: 3133327 BACKGROUND

• 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.

  PMID: 15817329 BACKGROUND

• 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.

  PMID: 12902891 BACKGROUND

• 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.

  PMID: 12957248 BACKGROUND

• 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.

  PMID: 16170164 RESULT

• 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.

  PMID: 35427469 DERIVED

• 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.

  PMID: 27598804 DERIVED

• 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.

  PMID: 25702876 DERIVED

MeSH Terms

Interventions

Neoadjuvant Therapy; Adjuvants, Pharmaceutic

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Limitations and Caveats

* Relatively short follow-up and low number of events. * The lack of patient-reported outcomes. * Our decision to include vascular events other than strictly cardiac events (e.g. the presence of CVA or thromboembolic disease).

Results Point of Contact

• Title: Dr. Almudena Zapatero
• Organization: Hospital Universitario de la Princesa; Health Research Institute IIS from Hospital Universitario de la Princesa

almudena.zapatero@salud.madrid.org

+34 91 520 23 15

Study Officials

• Almudena Zapatero, MD PhD, IP

  Grupo de Investigación Clínica en Oncología Radioterapia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2014
• First Posted: June 26, 2014
• Study Start: November 1, 2005
• Primary Completion: June 1, 2014
• Study Completion: September 24, 2020
• Last Updated: November 20, 2020
• Results First Posted: November 4, 2016

Record last verified: 2020-11

Locations

ES (1)