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

NCT02303327 | Active Not Recruiting Phase 3

• 1 other identifier: PCS VI
• Study Type: interventional
• Target: 307
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Acute and delayed toxicity differences measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.

  The acute toxicity will be evaluated at or before 90 days and for the delayed toxicity, it will be determined at 90 -180 days and after (persisting or appearing after 180 days).

Secondary Outcomes (9)

• Freedom from biochemical failure measured by PSA level.

  At 3 and 5 years.

• Rate of local failures measured by number of recurrences in the prostate.

  At 3 and 5 years.

• Rate of regional failures measured by number of recurrences in the lymph nodes.

  At 3 and 5 years.

• Rate of distant failures measured by number of metastases.

  At 3 and 5 years.

• Disease specific survival measured by number of deaths associated to the prostate cancer.

  At 5 years.

Study Arms (2)

ADT+EBRT+ HDR brachytherapy boost

OTHER

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).

Radiation: EBRT + HDR brachytherapy boost; Drug: Androgen deprivation therapy

ADT+Hypofractionated Dose Escalation RT

ACTIVE COMPARATOR

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

Radiation: Hypofractionated Dose Escalation Radiotherapy; Drug: Androgen deprivation therapy

Interventions

EBRT + HDR brachytherapy boost 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.

ADT+EBRT+ HDR brachytherapy boost

Hypofractionated Dose Escalation Radiotherapy RADIATION

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

ADT+Hypofractionated Dose Escalation RT

Androgen deprivation therapy DRUG

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

Also known as: ADT

ADT+EBRT+ HDR brachytherapy boost; ADT+Hypofractionated Dose Escalation RT

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sir Mortimer B. Davis - Jewish General Hospital: lead

Study Sites (12)

Eastern Health

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Lawson Health Research Institute

London, Ontario, N6C 2R5, Canada

Location

Windsor Regional Hospital

Windsor, Ontario, N8W2X3, Canada

Location

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

Gatineau, Quebec, J8P 7H2, Canada

Location

CHUM Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Montréal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Jewish General Hospital, McGill University

Montreal, Quebec, H3T 1E2, Canada

Location

CHUQ, L'Hôtel-Dieu de Québec

Québec, Quebec, G1R 2J6, Canada

Location

Centre de santé Rimouski-Neigette

Rimouski, Quebec, G5L 5T1, Canada

Location

CHUS - Hôpital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Centre Hospitalier régional de Trois-Rivières

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Related Publications (13)

• Canadian Cancer Statistics 2010. www.cancer.ca.

  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.

  PMID: 8364818 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

• 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.

  PMID: 19362783 BACKGROUND

• 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.

  PMID: 19395192 BACKGROUND

• 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.

  PMID: 16938815 BACKGROUND

• 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.

  PMID: 20047800 BACKGROUND

• 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.

  PMID: 10705005 BACKGROUND

• 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.

  PMID: 15718316 BACKGROUND

• 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.

  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.

  PMID: 21784585 BACKGROUND

• 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.

  PMID: 18172188 BACKGROUND

• 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.

  PMID: 10837944 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Androgen Antagonists

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Tamim Niazi, MD

  Jewish General Hospital, McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiation Oncologist

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: November 27, 2014
• Study Start: January 1, 2015
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2029
• Last Updated: December 9, 2024

Record last verified: 2024-12

Locations

CA (12)