Comparative Study of Radiotherapy Treatments to Treat High Risk Prostate Cancer Patients

NCT ID: NCT02303327

Last Updated: 2024-12-09

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

307 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2029-01-31

Brief Summary

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In North America, the number of new cases of prostate cancer increases every year. Many efforts have been made to develop more efficient and safer curative treatments for high risk prostate cancer patients.

This phase III clinical trial is designed to compare the safety of a standard pelvic external beam radiation therapy (EBRT) combined with a high dose rate brachytherapy (HDRB) boost (direct insertion of radiation source over a period of minutes via flexible needles temporarily inserted in the prostate) to a shorter course of hypofractionated dose escalation radiotherapy (larger radiation dose per daily treatment) in patients with high risk prostate cancer.

The investigators plan to recruit 296 patients across Quebec who will be randomized in either treatment plan.

Detailed Description

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In North America, the number of new cases of prostate cancer increases every year. To this day, the standard curative treatment for high risk prostate cancer patients is external beam radiation therapy (EBRT) combined with hormonal manipulation (Luteinizing hormone-releasing hormone LHRH agonists such as Eligard) to lower levels of testosterone to slow down or even stop the growth of prostate cancer. It has been recently demonstrated that combination of high dose rate brachytherapy (HDRB) boost (direct insertion of radiation source in the prostate for killing the tumor) to EBRT could be an effective treatment for prostate cancer patients. On the other hand, other recent studies have suggested that dose escalation and hypofractionated radiation delivery (larger radiation dose per daily treatment) can be more efficient than standard fractionation in prostate cancer patients.

This phase III clinical trial is designed to compare the safety of a conventional pelvic EBRT combined with a HDRB boost (i.e. 46 Gy in 23 fractions followed by a 15-Gy HDRB boost) to a shorter course of hypofractionated dose escalation radiotherapy (i.e. 68 Gy in 25 fractions) in patients with high risk prostate cancer. The patients will be randomized to either of the two different courses of treatment. All the patients will be also treated with hormonal therapy for a total duration of 28 months (2 months before radiation therapy (RT), 2 months during RT and for 24 months after RT). The patients will undergo different test before the treatment, such as bone scan, blood test, CT scan and bone density. The patient's follow-up will be the first month after start of RT, every 4 months for the first 2 years, then every 6 months the third year and then annually for 10 years. On every visit, the patient will undergo digital rectal examination (DRE) as well as evaluation of testosterone and prostate specific antigen (PSA) levels.

The safety of the new course of radiation therapy will be evaluated by the acute (at and before 90 days) and delayed toxicities (at 90 days, at 180 days and after) measured by Common Terminology Criteria for Adverse Events (CTCAE version 4). We will also determine Biochemical Failure Free Survival, Distant Metastasis Free Survival, Disease Specific Survival, Overall Survival and the Health-related Quality of Life using the Expanded Prostate Cancer Index Composite (EPIC). We will also monitor the development of gastrointestinal and genitourinary toxicities and establish the predictive value of PTEN deletion and TMPRSS2ETS fusion (genetic markers to predict the nature and progression of prostate tumors).

This study will be conducted through the Genitourinary Radiation Oncology Group of Quebec (GROUQ) in 12 selected radiation oncology centers. We plan to recruit 296 patients across Quebec and the recruitment should be completed within 24 months of activation.

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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ADT+EBRT+ HDR brachytherapy boost

Standard fractionation radiotherapy: 46 Gy in 23 fractions (EBRT) and a 15-Gy HDRB boost in conjunction with 28 months of androgen deprivation therapy (ADT).

Group Type OTHER

EBRT + HDR brachytherapy boost

Intervention Type RADIATION

Standard radiotherapy (EBRT, 23 fractions) with the addition of High Dose-Rate (HDR) brachytherapy boost within 3 weeks of beginning or finishing the EBRT.

Androgen deprivation therapy

Intervention Type DRUG

28 months of androgen deprivation therapy (injections every 4 months for a total of 28 months)

ADT+Hypofractionated Dose Escalation RT

Hypofractionated dose escalation radiotherapy: 68 Gy in 25 fractions in conjunction with 28 months of androgen deprivation therapy (ADT).

Group Type ACTIVE_COMPARATOR

Hypofractionated Dose Escalation Radiotherapy

Intervention Type RADIATION

Radiation therapy (higher radiation dose per treatment) will be given once a day, five days a week, over approximately 5 weeks.

Androgen deprivation therapy

Intervention Type DRUG

28 months of androgen deprivation therapy (injections every 4 months for a total of 28 months)

Interventions

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EBRT + HDR brachytherapy boost

Standard radiotherapy (EBRT, 23 fractions) with the addition of High Dose-Rate (HDR) brachytherapy boost within 3 weeks of beginning or finishing the EBRT.

Intervention Type RADIATION

Hypofractionated Dose Escalation Radiotherapy

Radiation therapy (higher radiation dose per treatment) will be given once a day, five days a week, over approximately 5 weeks.

Intervention Type RADIATION

Androgen deprivation therapy

28 months of androgen deprivation therapy (injections every 4 months for a total of 28 months)

Intervention Type DRUG

Other Intervention Names

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ADT

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed adenocarcinoma of the prostate diagnosed within 6 months prior to randomization, (if longer than 6 months, needs to be approved by the PI).
* Clinical stage including at least one of the following: T3 or T4, Gleason Score \> 8, and/ or Prostate-specific antigen (PSA) \> 20 (ng/ml or μg/L).
* Pelvic and para-aortic lymph nodes must be negative on CT scan or MRI of the abdomen and pelvis performed within 12 (recommended time limit, may exceed in certain cases) weeks prior to randomization. For patients who have started androgen suppression prior to randomization, CT or MRI may be done after start of therapy, provided it is done no more than 28 days following start of androgen suppression therapy (any lymph node appearing \> 1.5 cm on CT or MRI must be histologically negative by either needle aspirate or lymph node dissection performed within 12 weeks prior to randomization).
* Investigations, including chest x-ray (CXR is recommended and not mandatory) CT scan and bone scan (with radiographs of suspicious areas) have been performed within 12 weeks (recommended time limit) prior to randomization and are negative for metastases. For patients who have started androgen suppression prior to randomization, bone scan may be done up to and including 28 days after the commencement of therapy.
* Patients will have had a PSA test done at the time of diagnosis. This PSA test could be repeated within 28 days prior to randomization. The PSA value used to confirm high risk disease and the value to be entered on the eligibility checklist must be the higher of these two values. These criteria will be the same regardless of whether or not the patient has initiated hormone therapy prior to randomization.
* The patient may have received prior androgen suppression therapy provided that androgen suppression therapy commenced no more than 28 days prior to randomization.
* The patient must not have received any cytotoxic anticancer therapy for prostate cancer prior to randomization. Patients may have received treatment with a 5-alpha-reductase inhibitor (e.g. Finasteride) for benign prostatic hypertrophy (BPH), which must have been discontinued prior to the randomization.
* ECOG performance status must be 0 or 1.
* Hematology and Biochemistry: Laboratory requirements have been done within 28-42 days prior to randomization: hemoglobin \> 100 g/L, absolute Neutrophils \> 1.5 x 109/L, platelets \> 100 x 109/L, serum creatinine \< 1.5 x ULN

Exclusion Criteria

* Patients with a history of other malignancies, except: non-melanoma skin cancer; or other solid tumours curatively treated with no evidence of disease for \> 5 years.
* The presence of small-cell or transitional-cell carcinoma in the biopsy specimen.
* Patients who had previous chemotherapy for carcinoma of the prostate.
* Patients who had prior surgical treatment for carcinoma of the prostate apart from trans-urethral resection, including bilateral orchiectomy.
* Patients with any contraindication to pelvic radiotherapy: including, but not limited to, previous pelvic radiotherapy. Inflammatory bowel disease (at the discretion of the treating oncologist) or severe bladder irritability.
* Patients with serious non malignant disease resulting in a life expectancy less than 3 years.
* Other serious illness, psychiatric or medical condition that would not permit the patient to be managed according to the protocol including active uncontrolled infection and significant cardiac dysfunction. Patients with medical conditions that would contraindicate the treatment regimen outlined in the protocol \[e.g. intake of study drugs\].
* Known hypersensitivity to any protocol-indicated study medications.
* Presence of bilateral hip replacement prostheses.
* Patients with history of severe congestive heart failure will not be eligible.
* Patients with congenital long QT syndrome or patients taking Class IA, Class III or Class IC anti-arrhythmic medications will require a cardiologist's evaluation prior to eligibility assessment. Patients with cardiovascular diseases can be included as long as the benefits of androgen deprivation therapy outweigh the potential risk of cardiovascular events.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Sir Mortimer B. Davis - Jewish General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dr. Tamim Niazi

Radiation Oncologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tamim Niazi, MD

Role: PRINCIPAL_INVESTIGATOR

Jewish General Hospital, McGill University

Locations

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Eastern Health

St. John's, Newfoundland and Labrador, Canada

Site Status

Lawson Health Research Institute

London, Ontario, Canada

Site Status

Windsor Regional Hospital

Windsor, Ontario, Canada

Site Status

Centre Hospitalier des Vallées de l'Outaouais, Hôpital de Gatineau

Gatineau, Quebec, Canada

Site Status

CHUM Notre-Dame

Montreal, Quebec, Canada

Site Status

Montréal General Hospital

Montreal, Quebec, Canada

Site Status

Jewish General Hospital, McGill University

Montreal, Quebec, Canada

Site Status

CHUQ, L'Hôtel-Dieu de Québec

Québec, Quebec, Canada

Site Status

Centre de santé Rimouski-Neigette

Rimouski, Quebec, Canada

Site Status

CHUS - Hôpital Fleurimont

Sherbrooke, Quebec, Canada

Site Status

Centre Hospitalier régional de Trois-Rivières

Trois-Rivières, Quebec, Canada

Site Status

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Site Status

Countries

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Canada

References

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Canadian Cancer Statistics 2010. www.cancer.ca.

Reference Type BACKGROUND

Levy IG, Gibbons L, Collins JP, Perkins DG, Mao Y. Prostate cancer trends in Canada: rising incidence or increased detection? CMAJ. 1993 Sep 1;149(5):617-24.

Reference Type BACKGROUND
PMID: 8364818 (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)

McCammon R, Rusthoven KE, Kavanagh B, Newell S, Newman F, Raben D. Toxicity assessment of pelvic intensity-modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate for intermediate- and high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):413-20. doi: 10.1016/j.ijrobp.2008.10.050. Epub 2009 Apr 11.

Reference Type BACKGROUND
PMID: 19362783 (View on PubMed)

Pervez N, Small C, MacKenzie M, Yee D, Parliament M, Ghosh S, Mihai A, Amanie J, Murtha A, Field C, Murray D, Fallone G, Pearcey R. Acute toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):57-64. doi: 10.1016/j.ijrobp.2009.01.048.

Reference Type BACKGROUND
PMID: 19395192 (View on PubMed)

Hong TS, Tome WA, Jaradat H, Raisbeck BM, Ritter MA. Pelvic nodal dose escalation with prostate hypofractionation using conformal avoidance defined (H-CAD) intensity modulated radiation therapy. Acta Oncol. 2006;45(6):717-27. doi: 10.1080/02841860600781781.

Reference Type BACKGROUND
PMID: 16938815 (View on PubMed)

Arcangeli G, Saracino B, Gomellini S, Petrongari MG, Arcangeli S, Sentinelli S, Marzi S, Landoni V, Fowler J, Strigari L. A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2010 Sep 1;78(1):11-8. doi: 10.1016/j.ijrobp.2009.07.1691. Epub 2010 Jan 4.

Reference Type BACKGROUND
PMID: 20047800 (View on PubMed)

Hsu IC, Pickett B, Shinohara K, Krieg R, Roach M 3rd, Phillips T. Normal tissue dosimetric comparison between HDR prostate implant boost and conformal external beam radiotherapy boost: potential for dose escalation. Int J Radiat Oncol Biol Phys. 2000 Mar 1;46(4):851-8. doi: 10.1016/s0360-3016(99)00501-5.

Reference Type BACKGROUND
PMID: 10705005 (View on PubMed)

Sathya JR, Davis IR, Julian JA, Guo Q, Daya D, Dayes IS, Lukka HR, Levine M. Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol. 2005 Feb 20;23(6):1192-9. doi: 10.1200/JCO.2005.06.154.

Reference Type BACKGROUND
PMID: 15718316 (View on PubMed)

Guix B, et al. Treatment of Intermediate-or High-risk Prostate Cancer by Dose Escalation with High-dose 3D-conformal Radiotherapy (HD-3D-CRT) or Low-dose 3D-conformal Radiotherapy Plus HDR Brachytherapy (LD-3D-CRT+HDR-B): Early Results of a Prospective Comparative Trial. Int J Radiat Oncol Biol Phys. 78[3], S78. 11-1-2010.

Reference Type BACKGROUND

Cury FL, Duclos M, Aprikian A, Patrocinio H, Kassouf W, Shenouda G, Faria S, David M, Souhami L. Single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment of intermediate-risk prostate cancer - long term results. Int J Radiat Oncol Biol Phys. 2012 Mar 15;82(4):1417-23. doi: 10.1016/j.ijrobp.2011.05.025. Epub 2011 Jul 23.

Reference Type BACKGROUND
PMID: 21784585 (View on PubMed)

Roach M 3rd, Bae K, Speight J, Wolkov HB, Rubin P, Lee RJ, Lawton C, Valicenti R, Grignon D, Pilepich MV. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol. 2008 Feb 1;26(4):585-91. doi: 10.1200/JCO.2007.13.9881. Epub 2008 Jan 2.

Reference Type BACKGROUND
PMID: 18172188 (View on PubMed)

Roach M 3RD, Lu J, Pilepich MV, Asbell SO, Mohiuddin M, Terry R, Grignon D, Lawton C, Shipley W, Cox J. Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials. Int J Radiat Oncol Biol Phys. 2000 Jun 1;47(3):617-27. doi: 10.1016/s0360-3016(00)00577-0.

Reference Type BACKGROUND
PMID: 10837944 (View on PubMed)

Other Identifiers

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PCS VI

Identifier Type: -

Identifier Source: org_study_id