Clinical trial NCT03432780: Radiation-hormone and Docetaxel VS Radiation-hormone in Patients With High-Risk Localized Prostate Cancer
Official title: Randomized Phase II Clinical Study of Radiation Therapy, Hormone Therapy and Chemotherapy With Docetaxel Versus Radiation Therapy and Hormone Therapy in Patients With High-Risk Localized Prostate Cancer (Stage III and IV)"
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Prostate Cancer Stage III
Prostate Cancer Stage IV
Lead sponsor: Spanish Oncology Genito-Urinary Group
Sponsor class: OTHER
Collaborators: name: Pivotal S.L.
First posted: 2018-02-14
Enrollment: 134
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, multicenter, multidisciplinary, parallel-group, open-label study with randomized group assignment
Primary purpose: PREVENTION

Brief summary: A prospective, multicenter, parallel-group, open-label, randomized, phase II Clinical Study of Radiation Therapy, Hormone Therapy and Docetaxel Versus Radiation Therapy and Hormone Therapy in Patients with High-Risk Localized Prostate Cancer (Stage III and IV) whose primary objective is determine the percentage of patients free of biochemical recurrence within 5 years of receiving a combination of radiation therapy with docetaxel associated with hormone therapy or the standard of care of radiation therapy and hormone therapy in patients with stage III and IV localized prostate cancer with a poor prognosis.

Detailed description: Randomized Phase II Clinical Study of Radiation Therapy, Hormone Therapy and Chemotherapy with Docetaxel Versus Radiation Therapy and Hormone Therapy in Patients with High-Risk Localized Prostate Cancer (Stage III and IV) Primary Objective: To determine the percentage of patients free of biochemical recurrence within 5 years of receiving a combination of radiation therapy with docetaxel associated with hormone therapy or the standard of care of radiation therapy and hormone therapy in patients with stage III and IV localized prostate cancer with a poor prognosis.

Design: A prospective, multicenter, multidisciplinary, parallel-group, open-label study with randomized group assignment.

Eligibility criteria: Inclusion Criteria:

1. Histological confirmation of adenocarcinoma of the prostate.
2. Age \> 18 years.
3. Localized high-risk prostate cancer, defined as:

   * Stage III: T3 N0 M0, Gleason grade 8, 9, or 10, or
   * Stage IV: T4 N0 M0, any Gleason grade or Tx N1 M0, any Gleason grade
4. PSA \> 20 ng/mL.
5. Karnofsky index ≥ 70%
6. Good bone marrow reserve, with white blood cell count \> 3000/mm3, hemoglobin \>9.5 g/dL and platelets \> 150,000/mm3.
7. Absence of hepatic abnormality, with bilirubin values \< 1.5 mg/dL and with SGOT/SGPT values up to 2 times the upper limit of normality for each site.
8. Absence of abnormality in renal function, with creatinine levels up to 2 times the upper limit of normality for each site.
9. Having given informed consent in writing.

Exclusion Criteria:

1. Previous hormone treatment during more than 3 months.
2. Previous surgical treatment, pelvic radiation therapy, or chemotherapy for the current illness.
3. Concomitant second neoplasm or history of neoplastic disease in the last 5 years, except for cutaneous basal cell carcinoma.
4. Metabolic disease or uncontrolled systemic disease.
5. Previous history of grade III-IV neuropathy (NCI CTCAE v3).
6. Psychological, social, family, or geographical conditions that may compromise compliance with or follow-up of the study.
7. Having received treatment with an investigational medicinal product during the 30 days prior to inclusion in the study.
8. Inflammatory bowel disease.

Primary outcomes:
measure: Percentage of patients free of biochemical recurrence within 5 years of receiving a combination of radiation therapy with docetaxel associated with hormone therapy or the standard of care of radiation therapy and hormone therapy
timeFrame: 5 years of randomization
Secondary outcomes:
measure: Percentage of patients with biochemical recurrence-free survival
timeFrame: 5 years
measure: Percentage of patients with progression-free survival
timeFrame: 5 years
measure: Percentage of patients with overall survival.
timeFrame: 5 years
measure: Clinical response rate
timeFrame: 5 years
measure: Biochemical response rate.
timeFrame: 5 years
measure: Quality of life of the patients
timeFrame: screening and week 9
measure: Safety profile of the treatment.
timeFrame: 5 years
Other outcomes:
Locations:
Study officials:
References:
citation: Armstrong CM, Gao AC. Drug resistance in castration resistant prostate cancer: resistance mechanisms and emerging treatment strategies. Am J Clin Exp Urol. 2015 Aug 8;3(2):64-76. eCollection 2015.
citation: 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.
citation: Lawton CA, Winter K, Byhardt R, Sause WT, Hanks GE, Russell AH, Rotman M, Porter A, McGowan DG, DelRowe JD, Pilepich MV. Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85-31). Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1997 Jul 15;38(5):931-9. doi: 10.1016/s0360-3016(97)00288-5.
citation: Kumar P, Perrotti M, Weiss R, Todd M, Goodin S, Cummings K, DiPaola RS. Phase I trial of weekly docetaxel with concurrent three-dimensional conformal radiation therapy in the treatment of unfavorable localized adenocarcinoma of the prostate. J Clin Oncol. 2004 May 15;22(10):1909-15. doi: 10.1200/JCO.2004.02.001.
citation: Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. doi: 10.1056/NEJMoa040720.
citation: Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1513-20. doi: 10.1056/NEJMoa041318.
citation: Hennequin C, Giocanti N, Favaudon V. Interaction of ionizing radiation with paclitaxel (Taxol) and docetaxel (Taxotere) in HeLa and SQ20B cells. Cancer Res. 1996 Apr 15;56(8):1842-50.
citation: Mason KA, Hunter NR, Milas M, Abbruzzese JL, Milas L. Docetaxel enhances tumor radioresponse in vivo. Clin Cancer Res. 1997 Dec;3(12 Pt 1):2431-8.
citation: Kumar P. A new paradigm for the treatment of high-risk prostate cancer: radiosensitization with docetaxel. Rev Urol. 2003;5 Suppl 3(Suppl 3):S71-7.