PROPER2: Personalized Radiotherapy for Biochemical Recurrence of Prostate Cancer After Prostatectomy.

Sponsor

Lund University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04858880

Collaborator

(none)

374

Enrollment

Locations

Arms

107.7

Anticipated Duration (Months)

124.7

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A randomized phase III trial to study the effect of adding lymph node irradiation in patients with poor prostate-specific antigen (PSA) response during salvage radiotherapy for biochemical recurrence (0.15 ≤ PSA <0.70 ng/ml) after prostatectomy.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Radiation: Radiation to the prostate bed with or without addition of radiation of lymph node irradiation.	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

374 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Personalized Radiotherapy for Biochemical Recurrence of Prostate Cancer After Prostatectomy: a Randomized Phase III Study.

Actual Study Start Date :

Apr 9, 2021

Anticipated Primary Completion Date :

Apr 1, 2030

Anticipated Study Completion Date :

Apr 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Continued salvage radiotherapy + lymph node irradiation (non responders) Continued salvage radiotherapy as initially planned (to 70.0 Gy/73.5 Gy in 35 fractions to the prostate bed/local recurrence if present) + the addition of lymph node irradiation (46 Gy/23 fractions) given in sequence. Total number of fractions: 35 + 8 = 43 with 15 of the lymph node irradiation fractions delivered concomitant with the prostate bed/local recurrence irradiation. These patients are classified as non responders according to weekly PSA measurements during the first 4 weeks of radiotherapy.	Radiation: Radiation to the prostate bed with or without addition of radiation of lymph node irradiation. Radiation to the prostate bed with or without addition of radiation of lymph node irradiation (non responders). Patients with PSA response continues radiotherapy as initially planned, and are not followed according to the study protocol, only according to clinical practice.
Active Comparator: Continued salvage radiotherapy (non responders) Continued salvage radiotherapy as initially planned (to 70.0 Gy/73.5 Gy in 35 fractions to the prostate bed/local recurrence if present). These patients are classified as non responders according to weekly PSA measurements during the first 4 weeks of radiotherapy.	Radiation: Radiation to the prostate bed with or without addition of radiation of lymph node irradiation. Radiation to the prostate bed with or without addition of radiation of lymph node irradiation (non responders). Patients with PSA response continues radiotherapy as initially planned, and are not followed according to the study protocol, only according to clinical practice.
No Intervention: Continued salvage radiotherapy (responders) Continued salvage radiotherapy as initially planned (to 70.0 Gy/73.5 Gy in 35 fractions to the prostate bed/local recurrence if present). These patients are classified as responders according to weekly PSA measurements during the first 4 weeks of radiotherapy, and are not followed according to the study protocol, follow up according to clinical practice.

Arm

Intervention/Treatment

Experimental: Continued salvage radiotherapy + lymph node irradiation (non responders)

Continued salvage radiotherapy as initially planned (to 70.0 Gy/73.5 Gy in 35 fractions to the prostate bed/local recurrence if present) + the addition of lymph node irradiation (46 Gy/23 fractions) given in sequence. Total number of fractions: 35 + 8 = 43 with 15 of the lymph node irradiation fractions delivered concomitant with the prostate bed/local recurrence irradiation. These patients are classified as non responders according to weekly PSA measurements during the first 4 weeks of radiotherapy.

Radiation: Radiation to the prostate bed with or without addition of radiation of lymph node irradiation.

Radiation to the prostate bed with or without addition of radiation of lymph node irradiation (non responders). Patients with PSA response continues radiotherapy as initially planned, and are not followed according to the study protocol, only according to clinical practice.

Active Comparator: Continued salvage radiotherapy (non responders)

Continued salvage radiotherapy as initially planned (to 70.0 Gy/73.5 Gy in 35 fractions to the prostate bed/local recurrence if present). These patients are classified as non responders according to weekly PSA measurements during the first 4 weeks of radiotherapy.

Radiation: Radiation to the prostate bed with or without addition of radiation of lymph node irradiation.

No Intervention: Continued salvage radiotherapy (responders)

Continued salvage radiotherapy as initially planned (to 70.0 Gy/73.5 Gy in 35 fractions to the prostate bed/local recurrence if present). These patients are classified as responders according to weekly PSA measurements during the first 4 weeks of radiotherapy, and are not followed according to the study protocol, follow up according to clinical practice.

Outcome Measures

Primary Outcome Measures

Failure-free survival (FFS). [FFS after SRT, with failure defined as either biochemical or clinical recurrence (imaging or biopsy confirmed). FFS is calculated from the randomization date (arms A and B) until end of follow up (month 60 after]
Failure-free survival after salvage radiotherapy (SRT), with failure defined as either biochemical, defined as verified PSA level of ≥ 0.2 ng/ml above the post-radiotherapy PSA nadir value or clinical Recurrence, imaging or biopsy confirmed.

Secondary Outcome Measures

Systemic treatment-free survival. [Is evaluated from the randomization date (arms A and B) until end of follow up (month 60 after end of radiotherapy).]
Arms A and B will be compared regarding systemic treatment-free survival.
Distant metastasis-free survival. [Is evaluated from the randomization date (arms A and B) until end of follow up (month 60 after end of radiotherapy).]
Arms A and B will be compared regarding distant metastasis-free survival. survival.
Prostate cancer specific survival. [Is evaluated from the randomization date (arms A and B) until end of follow up (month 60 after end of radiotherapy).]
Arms A and B will be compared regarding prostate cancer specific survival survival.
Overall survival. [Is evaluated from the randomization date (arms A and B) until end of follow up (month 60 after end of radiotherapy).]
Arms A and B will be compared regarding overall survival.
Numbers of patients with acute toxicity (≤ 3 months after end of salvage radiotherapy). [Up to 3 months after end of salvage radiotherapy.]
Toxicity that will be evaluated is presence of cystitis, bladder spasm, incontinence, urinary urgency, urinary retention, nausea, diarrhea, colitis, ileus, bloating, bowel obstruction, bowel perforation, gastrointestinal hemorrhage, rectal mucositis, erectile dysfunction, fatigue, lymphedema, pain, blood toxicity.
Numbers of patients with late toxicity (> 3 months to 5 years after end of salvage radiotherapy). [After 3 months after end of salvage therapy until end of follow up at month 60 after end of salvage therapy.]
Toxicity that will be evaluated is presence of cystitis, bladder spasm, incontinence, urinary urgency, urinary retention, nausea, diarrhea, colitis, ileus, bloating, bowel obstruction, bowel perforation, gastrointestinal hemorrhage, rectal mucositis, erectile dysfunction, fatigue, lymphedema, pain, blood toxicity.
Patients self-esteem of quality of life. [Quality of life evaluated using questionnaire by the European Organisation for Research and Treatment of Cancer (EORTC), questionnaire is QLQ-C30. Is done at baseline, at end of radiotherapy (43 days in Arm A, 35 days in Arm B), month 12, 24, and 60.]
Arms A and B will be compared regarding quality of life.
Patients self-esteem of quality of life. [Quality of life evaluated using questionnaire by the European Organisation for Research and Treatment of Cancer (EORTC), questionnaire is QLQ - PR25. Is done at baseline, at end of radiotherapy (43 days in Arm A, 35 days in Arm, month 12, 24, and 60.]
Arms A and B will be compared regarding quality of life.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Life expectancy > 10 years
Age ≥18 years.
World Health Organization (WHO) performance status 0-1.
Estimated life expectancy >10 years.
Histological evidence of prostate cancer in the prostatectomy specimen
Primary tumor, regional nodes, metastasis (TNM): any primary tumor (pT), pathologically node-negative (pN0), M0.
Biochemical Recurrence (BCR) after prostatectomy, with 0.15 ≤ PSA <0.70 ng/ml.
Patients must be able to comply with the protocol.
Signed informed consent.
Adequate laboratory findings (Haemoglobin (Hb) >90g/L, absolute neutrophil count

1.0x109/L, platelets >75x109/l, bilirubin <1.5x upper limit of normal (ULN), alanine aminotransferase (ALAT) <5x ULN and creatinine <1.5 ULN).

Exclusion Criteria:

Metastases (regional lymph nodes or distant)* diagnosed with imaging.
Prior or ongoing hormonal therapy (antiandrogens or gonadotropin releasing hormone).
Prior radiotherapy to the pelvis.
Prior malignancy other than prostate cancer and basalioma in the past five years.
Clinically significant (i.e. active) cardiovascular disease e.g. myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) class III-IV congestive heart failure.
Severe pulmonary disease.
Any other serious or uncontrolled illness which in the opinion of the investigator makes it undesirable for the patient to enter the trial.