Conformal Radiotherapy (CRT) Alone Versus CRT Combined With HDR BT or Stereotactic Body Radiotherapy for Prostate Cancer

NCT ID: NCT01839994

Last Updated: 2013-04-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2018-12-31

Brief Summary

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The purpose of this study is to compare the outcomes of conventionally fractionated conformal radiotherapy with CF-CRT combined with either high-dose-rate brachytherapy or stereotactic body radiotherapy for intermediate or high-risk prostate cancer patients.

Detailed Description

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Prostate cancer is considered as a disease with relatively slow natural course and good clinical prognosis. Such description, however, does not well refer to intermediate and high-risk cases where long-term rate of biochemical progression remains not satisfactory, and the available treatment modalities entail a considerable morbidity. Over the last decade several competitive therapeutic approaches have evolved in curative treatment for intermediate and high-risk prostate cancer. The use of intensity-modulated radiation therapy (IMRT) made possible to escalate the total dose to the prostate without excessive toxicity.

Based on assumption of low value of low α/β value for adenocarcinoma of prostate, there is a potential of escalating the biological dose to the tumor with higher dose per fraction. High-dose-rate brachytherapy (HDR-BT) is one of the options, with the ability to conform radiation dose to the prostate with sharp dose gradient adjacent to critical organs. An increasing number of studies suggest its usefulness as a boost in intermediate and high risk disease. The randomized trial conducted in UK compared external beam radiotherapy (EBRT) alone with EBRT and HDR brachytherapy as a boost. Combining EBRT with HDR BT - boost resulted in significantly higher relapse-free-survival (RFS) with comparable incidence of severe late toxicity. However, the total dose used in EBRT alone - arm and radiotherapy technique may be considered suboptimal according to current standards.

Stereotactic body radiotherapy (SBRT) may be an interesting alternative to HDR brachytherapy, not requiring implantation of multiple catheters and anesthesia. SBRT boost for advanced localized prostate cancer has the potential to reduce toxicity while escalating the dose. First results of trials combining conventional irradiation with hypofractionated stereotactic boost and institutional pilot results gave promising outcome.

The comparison of these modalities of radiation therapy for prostate cancer will be performed in the current phase III trial study.

Conditions

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Prostate Cancer

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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CF-CRT combined with BT or SBRT boost

Conventionally fractionated CRT (IMRT or Rapid Arc) to the TD of 50 Gy, 2.0 Gy d fx, 5 days a week over the period of 5 weeks AND two 10 Gy fractions of real- time HDR brachytherapy OR CRT combined with two stereotactic body radiotherapy boosts of 10 Gy per fraction delivered with dynamic SBRT technique (IMRT or Rapid Arc).

The choice between two ways of delivering radiation dose to the boost volume will be based solely on clinical criteria, decision made by interdisciplinary team, according to the institutional protocol (in non-randomized fashion).

Hormonal treatment: three months of neoadjuvant androgen deprivation (MAB -maximal androgen blockade) in all patients. Long-term (3 years) of adjuvant hormonotherapy (LHRH agonists only) in high risk patients.

Group Type EXPERIMENTAL

CF-CRT combined with BT or SBRT boost.

Intervention Type RADIATION

CF-CRT to the prostate and SV (IM risk group) or to the prostate, SV and LN (high risk group) to the TD of 50 Gy, 2.0 Gy d fx, 5 days a week over the period of 5 weeks AND A. Two 10 Gy fractions of HDR BT 1-7 d. before external beam radiotherapy and one 1-7 d. after external beam radiotherapy OR B. Two stereotactic body radiotherapy (SBRT) fractions of 10 Gy to the prostate (CTV boost) delivered with dynamic SBRT technique (IMRT or Rapid Arc). First and second fraction of SBRT boost is scheduled 1-7 d. before and 1-7 d. after the start of conventionally fractionated radiotherapy, respectively.

Hormonal treatment (neoadjuvant androgen deprivation)

Intervention Type DRUG

Hormonal treatment: three months of neoadjuvant androgen deprivation (MAB -maximal androgen blockade) in all patients. Long-term (3 years) of adjuvant hormonotherapy (LHRH agonists only) in high risk patients.

CF-CRT alone

Conventionally fractionated external beam conformal radiotherapy (IMRT or Rapid Arc) to the prostate and seminal vesicles (intermediate risk group) or to the prostate, SV and pelvic lymph nodes (high risk group) to the total dose of 50 Gy in 2.0 Gy per fraction, 5 days a week over the period of 5 weeks, followed by a boost to the prostate (26 or 28 Gy in 2.0 Gy per fraction 5 days a week over the period of 2.5 weeks) to the total dose of 76 or 78 Gy (intermediate or high risk group of patients, respectively).

Hormonal treatment: three months of neoadjuvant androgen deprivation (MAB -maximal androgen blockade) in all patients. Long-term (3 years) of adjuvant hormonotherapy (LHRH agonists only) in high risk patients.

Group Type ACTIVE_COMPARATOR

CF-CRT alone

Intervention Type RADIATION

Conventionally fractionated EB-CRT (IMRT or Rapid Arc) to the TD of 50 Gy, followed by a boost to the prostate (26 or 28 Gy in 2.0 Gy per fraction 5 days a week over the period of 2.5 weeks) to the total dose of 76 or 78 Gy (intermediate or high risk group of patients, respectively).of 50 Gy in 2.0 Gy per fraction, 5 days a week over the period of 5 weeks, followed by a boost to the prostate (26 or 28 Gy in 2.0 Gy per fraction 5 days a week over the period of 2.5 weeks) to the total dose of 76 or 78 Gy (intermediate or high risk group of patients, respectively).

Hormonal treatment (neoadjuvant androgen deprivation)

Intervention Type DRUG

Hormonal treatment: three months of neoadjuvant androgen deprivation (MAB -maximal androgen blockade) in all patients. Long-term (3 years) of adjuvant hormonotherapy (LHRH agonists only) in high risk patients.

Interventions

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CF-CRT combined with BT or SBRT boost.

CF-CRT to the prostate and SV (IM risk group) or to the prostate, SV and LN (high risk group) to the TD of 50 Gy, 2.0 Gy d fx, 5 days a week over the period of 5 weeks AND A. Two 10 Gy fractions of HDR BT 1-7 d. before external beam radiotherapy and one 1-7 d. after external beam radiotherapy OR B. Two stereotactic body radiotherapy (SBRT) fractions of 10 Gy to the prostate (CTV boost) delivered with dynamic SBRT technique (IMRT or Rapid Arc). First and second fraction of SBRT boost is scheduled 1-7 d. before and 1-7 d. after the start of conventionally fractionated radiotherapy, respectively.

Intervention Type RADIATION

CF-CRT alone

Conventionally fractionated EB-CRT (IMRT or Rapid Arc) to the TD of 50 Gy, followed by a boost to the prostate (26 or 28 Gy in 2.0 Gy per fraction 5 days a week over the period of 2.5 weeks) to the total dose of 76 or 78 Gy (intermediate or high risk group of patients, respectively).of 50 Gy in 2.0 Gy per fraction, 5 days a week over the period of 5 weeks, followed by a boost to the prostate (26 or 28 Gy in 2.0 Gy per fraction 5 days a week over the period of 2.5 weeks) to the total dose of 76 or 78 Gy (intermediate or high risk group of patients, respectively).

Intervention Type RADIATION

Hormonal treatment (neoadjuvant androgen deprivation)

Hormonal treatment: three months of neoadjuvant androgen deprivation (MAB -maximal androgen blockade) in all patients. Long-term (3 years) of adjuvant hormonotherapy (LHRH agonists only) in high risk patients.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Pathologically proven adenocarcinoma of the prostate
2. Clinical stage T1-T3a (Intermediate or high risk features according to NCCN criteria)
3. No evidence of nodal or distant spread as determined by chest X-ray, bone scan and abdominal ultrasound or CT-scan or other investigations such as Positron Emission Tomography \[PET\] scan if required
4. No evidence of bulky spread beyond the capsule of the prostate, no seminal vesicle involvement assessed by TRUS or MRI of pelvis.
5. Good performance status (ZUBROD \<2, Karnofsky index \>=80%).
6. No contradictions for spinal anesthesia.
7. No contradictions for hormonal treatment (androgen deprivation).
8. Adequate bone marrow, renal and liver function.
9. Life expectancy in excess of 5 years.
10. No prior malignancy, except basal or squamous cell skin cancer.
11. Informed consent for participation in the study (confirmed by the signature together with the standard medical consent form for radiotherapy within the pelvis)

Exclusion Criteria

1. Different histology than adenocarcinoma.
2. Previous or concurrent malignancy, with the exception of basal cell carcinoma of the skin.
3. Locally advanced disease: bulky T3a and/or T3b.
4. Presence of metastatic disease (nodal and/or distant).
5. PSA \>100ng/ml
6. Any previous therapy other than hormonal treatment.
7. Concurrent uncontrolled medical conditions.
8. Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
9. Withdrawal of informed consent.

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Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Maria Sklodowska-Curie National Research Institute of Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rafał Suwiński, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland

Locations

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Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch

Gliwice, Silesian Voivodeship, Poland

Site Status

Countries

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Poland

Central Contacts

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Katarzyna Behrendt, MD

Role: CONTACT

+4832278818

Rafał Suwiński, MD, PhD

Role: CONTACT

+48322788806

Facility Contacts

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Katarzyna Behrendt, MD

Role: primary

+4832278818

Rafał Suwiński, MD, PhD

Role: backup

+4832278806

References

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Zelefsky MJ, Chan H, Hunt M, Yamada Y, Shippy AM, Amols H. Long-term outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer. J Urol. 2006 Oct;176(4 Pt 1):1415-9. doi: 10.1016/j.juro.2006.06.002.

Reference Type BACKGROUND
PMID: 16952647 (View on PubMed)

Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, Lee AK, Pollack A. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):67-74. doi: 10.1016/j.ijrobp.2007.06.054. Epub 2007 Aug 31.

Reference Type BACKGROUND
PMID: 17765406 (View on PubMed)

Pieters BR, de Back DZ, Koning CC, Zwinderman AH. Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: a systematic review. Radiother Oncol. 2009 Nov;93(2):168-73. doi: 10.1016/j.radonc.2009.08.033. Epub 2009 Sep 11.

Reference Type BACKGROUND
PMID: 19748692 (View on PubMed)

Martinez AA, Gustafson G, Gonzalez J, Armour E, Mitchell C, Edmundson G, Spencer W, Stromberg J, Huang R, Vicini F. Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer. Int J Radiat Oncol Biol Phys. 2002 Jun 1;53(2):316-27. doi: 10.1016/s0360-3016(02)02733-5.

Reference Type BACKGROUND
PMID: 12023135 (View on PubMed)

Martinez AA, Gonzalez J, Ye H, Ghilezan M, Shetty S, Kernen K, Gustafson G, Krauss D, Vicini F, Kestin L. Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-dose-rate boost and external beam radiotherapy. Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):363-70. doi: 10.1016/j.ijrobp.2009.10.035.

Reference Type BACKGROUND
PMID: 21195875 (View on PubMed)

Hoskin PJ, Rojas AM, Bownes PJ, Lowe GJ, Ostler PJ, Bryant L. Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer. Radiother Oncol. 2012 May;103(2):217-22. doi: 10.1016/j.radonc.2012.01.007. Epub 2012 Feb 16.

Reference Type BACKGROUND
PMID: 22341794 (View on PubMed)

Miralbell R, Molla M, Rouzaud M, Hidalgo A, Toscas JI, Lozano J, Sanz S, Ares C, Jorcano S, Linero D, Escude L. Hypofractionated boost to the dominant tumor region with intensity modulated stereotactic radiotherapy for prostate cancer: a sequential dose escalation pilot study. Int J Radiat Oncol Biol Phys. 2010 Sep 1;78(1):50-7. doi: 10.1016/j.ijrobp.2009.07.1689. Epub 2009 Nov 10.

Reference Type BACKGROUND
PMID: 19910135 (View on PubMed)

Quon H, Cheung PC, Loblaw DA, Morton G, Pang G, Szumacher E, Danjoux C, Choo R, Kiss A, Mamedov A, Deabreu A. Quality of life after hypofractionated concomitant intensity-modulated radiotherapy boost for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2012 Jun 1;83(2):617-23. doi: 10.1016/j.ijrobp.2011.07.005. Epub 2011 Nov 11.

Reference Type BACKGROUND
PMID: 22079736 (View on PubMed)

Jabbari S, Weinberg VK, Kaprealian T, Hsu IC, Ma L, Chuang C, Descovich M, Shiao S, Shinohara K, Roach M 3rd, Gottschalk AR. Stereotactic body radiotherapy as monotherapy or post-external beam radiotherapy boost for prostate cancer: technique, early toxicity, and PSA response. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):228-34. doi: 10.1016/j.ijrobp.2010.10.026. Epub 2010 Dec 22.

Reference Type BACKGROUND
PMID: 21183287 (View on PubMed)

Oermann EK, Slack RS, Hanscom HN, Lei S, Suy S, Park HU, Kim JS, Sherer BA, Collins BT, Satinsky AN, Harter KW, Batipps GP, Constantinople NL, Dejter SW, Maxted WC, Regan JB, Pahira JJ, McGeagh KG, Jha RC, Dawson NA, Dritschilo A, Lynch JH, Collins SP. A pilot study of intensity modulated radiation therapy with hypofractionated stereotactic body radiation therapy (SBRT) boost in the treatment of intermediate- to high-risk prostate cancer. Technol Cancer Res Treat. 2010 Oct;9(5):453-62. doi: 10.1177/153303461000900503.

Reference Type BACKGROUND
PMID: 20815416 (View on PubMed)

Other Identifiers

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CRT/BT/SBRT-COI-02

Identifier Type: -

Identifier Source: org_study_id

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