Radiotherapy Plus Hormone Therapy in Biochemically-relapsing Prostate Cancer Patients Following Surgery (CARLHA)

Safety and Efficacy of Radiotherapy Combined With a 6-month LH-RH Agonist and Abiraterone Hormone Therapy Treatment in Biochemically-relapsing Prostate Cancer Following Surgery

As there is no prospective data on the combination of abiraterone and salvage radiotherapy, the aim of this study is to further evaluate the safety profile of abiraterone acetate plus prednisone in patients with prostate cancer who are biochemically relapsing after surgery and undergo salvage radiotherapy with 6-months LH-RH agonist.

The investigators hypothesize that the toxicity profile of both treatments should not potentiate each other. This study will also provide preliminary data on the efficacy of this combination.

Study Overview

• Status: Completed
• Conditions: Biochemically-relapsing Prostate Adenocarcinoma Following Radical Prostatectomy
• Intervention / Treatment: Drug: Abiraterone

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Institut Bergonie
  • Caen, France
    • Centre François Baclesse
  • Dijon, France
    • Centre Georges François Leclerc
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest/Rene Gauducheau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Histologically confirmed prostate adenocarcinoma
2. The patients should have undergone only surgery for localized prostate adenocarcinoma: pT2, pT3 or pT4 with bladder neck involvement
3. pN0: negative lymphadenectomy at the time of prostatectomy
4. At inclusion the patients should have no clinical signs of progressive disease and should be M0 (bone and pelvic scans).
5. ≥ 18 years of age with life expectancy ≥ 10 years
6. Performance Status (ECOG) ≤ 1
7. PSA ≤ 0.1 ng/ml after prostatectomy (dosage performed within 2 months after surgery)
8. PSA ≥ 0.2 ng/ml et ≤ 2 ng/ml at the time of inclusion
9. Elevation of PSA over three consecutive assays performed in the same laboratory, with a minimal interval of two months between assays, (PSA nadir level followed by two other progressive assays)
10. At least 6 months between surgery and biochemical relapse
11. Serum potassium ≥ 3.5 mmol/L in the 72 hours before first dose of abiraterone acetate
12. Serum creatinine < 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min

13. Liver function:

    Serum bilirubin < 1.5 x ULN (except for patients with documented Gilbert's disease) AST and ALT < 2.5 x ULN

14. Patients must be affiliated to a Social Security System.
15. Patient information and written informed consent form signed for both principal and additional research
16. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria:

1. pN1: histologically-proven lymph node involvement at initial lymphadenectomy
2. Histology other than adenocarcinoma
3. Previous hormone therapy including prior therapy with ketoconazole or other CYP17 inhibitor(s) for prostate cancer.
4. Patients being treated within the last 14 days prior to inclusion with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A4 (Clarithromycin, Ketoconazole, Itraconazole, Voriconazole, Ritanovir, see appendix 11) or requiring those treatments during the study
5. Active or symptomatic viral hepatitis or chronic liver disease
6. Surgical or chemical castration
7. History of cancer, with the exception of basal cell carcinoma or any other cancer treated in the 5 years before inclusion and in complete remission.
8. Previous pelvic radiotherapy
9. Uncontrolled hypertension (defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy (see appendix 10 for mandatory BP measurement guidelines)
10. Severe and moderate hepatic impairment (Child-Pugh class B and C)

11. Patients with severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to:

    Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline

12. Known hypersensitivity to any of the study drugs or excipients.
13. Galactosemia, Glucose-galactose malabsorption or lactase deficiency
14. Patients with any psychological, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
15. Individual deprived of liberty or placed under the authority of a tutor.
16. Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within a period of 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: abiraterone; Abiraterone acetate (three dose levels in phase I) + prednisone (10mg/day)+LHRH + Radiotherapy	Drug: Abiraterone; Abiraterone acetate 1000mg/day + prednisone alone for one month before initiating the sequence of radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
to determine the maximum tolerated dose and the phase II recommended dose of abiraterone acetate treatment plus prednisone and LH-RH agonist combined with prostate radiotherapy	within 11 weeks after Radiotherapy initiation

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the 3-year biochemical relapse-free survival	3 years

Other Outcome Measures

Outcome Measure	Time Frame
overall safety profile	3 years

Collaborators and Investigators

• Sponsor: UNICANCER

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2012
• Primary Completion (Actual): January 7, 2022
• Study Completion (Actual): January 7, 2022

Study Registration Dates

• First Submitted: January 29, 2013
• First Submitted That Met QC Criteria: January 29, 2013
• First Posted (Estimate): January 30, 2013

Study Record Updates

• Last Update Posted (Actual): May 19, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: abiraterone; prostate adenocarcinoma; biochemically-relapsing
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: GEP12-UC-0101/1104; 2011-004831-30 (EudraCT Number)