Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202305854600529 Date of Approval: 22/05/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Quality of Life and Survival Outcomes of Metastatic Prostate Cancer Patients Treated with Prostate Directed Radiotherapy
Official scientific title Evaluating the Outcomes and Tolerability of Adding Local Radical Prostate Radiotherapy to the Standard of Care in Metastatic Prostate Cancer Patients
Brief summary describing the background and objectives of the trial Background: The role of cytoreductive local radiotherapy in metastatic prostate cancer has recently been established. This study focused on the clinical and survival outcomes of local radiotherapy in metastatic prostate cancer. The impact of local radiation treatment on patient-reported health-related quality of life significantly influences the prognosis of metastatic prostate cancer Aim: The study is challenging to establish the best lines of management of metastatic prostate cancer patients to improve the disease outcomes regarding local control of symptoms, survival, and quality of life through evaluating the outcomes and tolerability of combining local prostate-directed radiotherapy with standard systemic therapies. Primary Objectives: 1. To assess clinical and radiological response after adding local radiotherapy to the standard of care versus standard of care only. 2. To measure and compare progression free survival in local radiotherapy added to the standard of care arm versus the standard of care only arm. 3. To assess and report early and late adverse events and possible toxicities after the addition of local radiotherapy to the standard treatment. 4. To evaluate various quality of life domains after adding local radiotherapy to the standard treatment versus the standard treatment only. 6. To stratify and subgroup metastatic prostate cancer patients based on metastatic burden of disease into low metastatic volume and high metastatic volume prostate cancer. Secondary Objectives: 1. To measure overall survival in local radiotherapy added to the standard of care arm versus the standard of care only arm. 2. To determine the clinicopathological features of metastatic prostate cancer patients.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 01/11/2020
Actual trial start date 23/11/2020
Anticipated date of last follow up 01/11/2022
Actual Last follow-up date 21/11/2022
Anticipated target sample size (number of participants) 50
Actual target sample size (number of participants) 63
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Permuted block randomization Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Radical local prostate radiotherapy We used the conventional fractionation regimen of radiation dose 70Gy which was delivered in 35 fractions over 7 weeks duration (1.8Gy/fraction). Alternatively, the hypofractionation regimen of 55Gy in 20 fractions was also used (2.75Gy/fraction) 4 weeks for the hypofractionated schedule and 7 weeks for the conventionally fractionated schedule All metastatic prostate cancer patients were treated with the standard ADT (Gonadotropin hormone–releasing hormone agonist ± bicalutamide) or underwent orchiectomy 2 months prior to randomization. Local external beam radiotherapy was delivered as one of two regimens either: conventional regimen 70 Gy in 35 daily fractions of 2 Gy over 7 weeks, or hypofractionated regimen 55 Gy in 20 daily fractions of 2.75 Gy over 4 weeks. Patients were simulated in supine position with an empty rectum and comfortably full bladder. Pelvic immobilization was ensured using knee support. Planning CT scans were acquired without intravenous contrast. We used forward planned three-dimensional (3D) conformal radiotherapy with planning target volume (PTV) that included the prostate with 10 mm margin circumferentially except posteriorly (6 mm) and the proximal 2 cm of seminal vesicles. We didn’t include elective pelvic nodal irradiation in the field. Patients were followed up weekly during radiotherapy, then 1 month after finishing radiotherapy, then every 3 months for a year. All patients were then requested to fill in the questionnaire; European Organization for Research and Treatment of Cancer Quality-of- Life Questionnaire Prostate Module (EORTC-QLQ-PR25) at baseline then every 3 months throughout the study. This module was composed of multi-item scales to measure prostate cancer specific health-related quality of life outcomes. We used this questionnaire to measure baseline HRQoL in metastatic prostate cancer patients who were receiving the standard of care and to determine changes in patient reported HRQoL after local radiotherapy (Appendix A). Early and late genitourinary and gastrointestinal toxicity symptoms were reported at baseline, then every 3 months at regular follow-up visits or when serious adverse events develop. These adverse events were reported and graded in patients allocated to prostate radiotherapy using the Radiation Therapy Oncology Group (RTOG) scale (11). Early toxicity was recorded during the first 90 days post-radiation whereas late toxicity was recorded after the first 90 days following radiation treatment. The metastatic burden of the disease was assessed through CT and bone scans and classified according to the CHAARTED definition. 34
Control Group Standard of care androgen deprivation therapy Goserelin acetate 3.6 mg every 28 days ± bicalutamide 50 mg PO daily. Lifelong The control arm receiving the standard androgen deprivation either surgically through bilateral orchiectomy or medically by LHRH agonist; Goserelin acetate 3.6 mg every 28 days ± bicalutamide 50 mg PO daily. 29 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Patients diagnosed with metastatic prostate cancer who were receiving standard of care, androgen deprivation therapy and were: • Patients scored performance status 0-2 according to Eastern Cooperative Oncology Group (ECOG) performance scale. • Histologically proven adenocarcinoma of the prostate. • De-novo (synchronous) and metachronous metastatic prostate cancer patients. • Low volume metastatic prostate cancer (< 4 bone metastases) according to CHAARTED definition. • High-volume metastatic prostate cancer (≥ 4 bone metastases at least 1 beyond spine or pelvis, ± visceral metastases) according to CHAARETED definition. • No previous radical prostatectomy. • With or without nodal involvement. • Adequate hematological profile; Hemoglobin ≥ 10.0 g/dl, neutrophil count ≥1500 cells/mm3 and platelets ≥100000/mL before the start of treatment. • Written informed consent. Patients scored PS > 2 according to ECOG performance scale. • Presence of other diagnosed malignancies • Previous radical prostatectomy. • Previous local prostate radiotherapy or brachytherapy. • Presence of brain metastases or leptomeningeal metastases. Aged: 65+ Year(s) 50 Year(s) 85 Year(s) Male
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/03/2020 Research Ethics Committee Faculty of Medicine Suez Canal University
Ethics Committee Address
Street address City Postal code Country
Faculty of Medicine - Suez Canal University Circular Road, Ismailia, Egypt, 411522 Al Ismailiyya 411522 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. Clinical and radiological response after adding local radiotherapy to the standard of care versus standard of care only. 2. progression free survival 3. Early and late adverse events and possible toxicities after the addition of local radiotherapy to the standard treatment. 4. Patient reported Health related quality of life after radiation treatment versus the standard treatment only. 3 months, 6 months, 9 months and 12 months
Secondary Outcome Overal survival, Clinicopathological features of metastatic prostate cancer 3 months, 6 months, 9 months, 12 months interval
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Department of Clinical Oncology and Nuclear Medicine Suez Canal University Hospital Ring road kilo 4.5 Ismailia 40451 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
The principal investigator Salah El-Deen El-Ayoubi st., Building 6R Ismailia 41511 Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Suez Canal University Ring Road kilo 4.5 Al Ismailiyya 40451 Egypt University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Heba Ayoub Pgs.000936596@med.suez.edu.eg 01285663153 Salah El Din El Ayoubi st.
City Postal code Country Position/Affiliation
Al Ismailiyya 40451 Egypt Assistant Lecturer of Clinical Oncology MSc
Role Name Email Phone Street address
Scientific Enquiries Fifi El Sayef fifimostafa@gmail.com +201028278685 Reda street
City Postal code Country Position/Affiliation
Al Ismailiyya 40451 Egypt Lecturer of Clinical Oncology and Nuclear Medicine MD
Role Name Email Phone Street address
Public Enquiries Eman El Semary Eman.semary87@gmail.com +2010056634 Salah El Din El Ayoubi St.
City Postal code Country Position/Affiliation
Al Ismailiyya 40451 Egypt Lecturer of Clinical Oncology and Nuclear Medicine MD
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Yes, individual participant data will be available to other researchers. All individual participant data were collected during the study after deidentification. Data will be available immediately following publication to any researcher who wishes to access the data. Data will be available indefinitely after publication. Informed Consent Form,Study Protocol 12 months Data could be easily accessed and communicated by contacting email of the principal investigator: Pgs.000936596@med.suez.edu.eg
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://medsuezedu-my.sharepoint.com/personal/pgs_000936596_med_suez_edu_eg/Documents/Documents/Results/ Yes 17/05/2023
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 17/05/2023
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks https://drive.google.com/file/d/1c2rKWkPUPl5QtBw8Pm8BSj87DLMuvXun/view?usp=drivesdk
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 16/05/2023 The background of the study was added The study is challenging to establish the best lines of management of metastatic prostate cancer patients to improve the disease outcomes regarding local control of symptoms, survival, and quality of life through evaluating the outcomes and tolerability of combining local prostate-directed radiotherapy with standard systemic therapies. Primary Objectives: 1. To assess clinical and radiological response after adding local radiotherapy to the standard of care versus standard of care only. 2. To measure and compare progression free survival in local radiotherapy added to the standard of care arm versus the standard of care only arm. 3. To assess and report early and late adverse events and possible toxicities after the addition of local radiotherapy to the standard treatment. 4. To evaluate various quality of life domains after adding local radiotherapy to the standard treatment versus the standard treatment only. 6. To stratify and subgroup metastatic prostate cancer patients based on metastatic burden of disease into low metastatic volume and high metastatic volume prostate cancer. Secondary Objectives: 1. To measure overall survival in local radiotherapy added to the standard of care arm versus the standard of care only arm. 2. To determine the clinicopathological features of metastatic prostate cancer patients. Background: The role of cytoreductive local radiotherapy in metastatic prostate cancer has recently been established. This study focused on the clinical and survival outcomes of local radiotherapy in metastatic prostate cancer. The impact of local radiation treatment on patient-reported health-related quality of life significantly influences the prognosis of metastatic prostate cancer Aim: The study is challenging to establish the best lines of management of metastatic prostate cancer patients to improve the disease outcomes regarding local control of symptoms, survival, and quality of life through evaluating the outcomes and tolerability of combining local prostate-directed radiotherapy with standard systemic therapies. Primary Objectives: 1. To assess clinical and radiological response after adding local radiotherapy to the standard of care versus standard of care only. 2. To measure and compare progression free survival in local radiotherapy added to the standard of care arm versus the standard of care only arm. 3. To assess and report early and late adverse events and possible toxicities after the addition of local radiotherapy to the standard treatment. 4. To evaluate various quality of life domains after adding local radiotherapy to the standard treatment versus the standard treatment only. 6. To stratify and subgroup metastatic prostate cancer patients based on metastatic burden of disease into low metastatic volume and high metastatic volume prostate cancer. Secondary Objectives: 1. To measure overall survival in local radiotherapy added to the standard of care arm versus the standard of care only arm. 2. To determine the clinicopathological features of metastatic prostate cancer patients.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial phase 02/09/2023 It was designed as a phase 2 trial due to the small sample size Phase-3 Phase-2
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial phase 07/09/2023 the study was designed as phase 3 randomized controlled study Phase-2 Phase-3
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 16/05/2023 In fact, the sample size was estimated as 50 participants. But there was a misunderstanding about the required target number. By 70, I meant the total number of actually recruited or enrolled patients in this study. 70 50
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 16/05/2023 63 patients were randomly assigned to either prostate radiotherapy or control groups. We excluded 7 patients who didn't meet the inclusion criteria. 70 63
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 16/05/2023 This is the required form of the authentic ethics approval letter TRUE, Dr. Amira Gamal , Faculty of Medicine - Suez Canal University Circular Road, Ismailia, Egypt, 411522, Al Ismailiyya, 411522, Egypt, , 01 Mar 2021, +20643200789, rec@med.Suez.edu.eg, 25510_24355_4737.pdf TRUE, Research Ethics Committee Faculty of Medicine Suez Canal University, Faculty of Medicine - Suez Canal University Circular Road, Ismailia, Egypt, 411522, Al Ismailiyya, 411522, Egypt, , 01 Mar 2021, +20643200789, rec@med.Suez.edu.eg, 25510_24355_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 11/07/2023 There was a fault in the saved date of ethics approval TRUE, Research Ethics Committee Faculty of Medicine Suez Canal University, Faculty of Medicine - Suez Canal University Circular Road, Ismailia, Egypt, 411522, Al Ismailiyya, 411522, Egypt, , 01 Mar 2021, +20643200789, rec@med.Suez.edu.eg, 25510_24355_4737.pdf TRUE, Research Ethics Committee Faculty of Medicine Suez Canal University, Faculty of Medicine - Suez Canal University Circular Road, Ismailia, Egypt, 411522, Al Ismailiyya, 411522, Egypt, , 01 Mar 2020, +20643200789, rec@med.Suez.edu.eg, 25510_24355_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 16/05/2023 I want to update the authentic ethics approval letter TRUE, Dr. Amira Gamal , Faculty of Medicine - Suez Canal University Circular Road, Ismailia, Egypt, 411522, Al Ismailiyya, 411522, Egypt, , 01 Mar 2021, +20643200789, rec@med.Suez.edu.eg, 25510_24355_4737.pdf TRUE, Dr. Amira Gamal , Faculty of Medicine - Suez Canal University Circular Road, Ismailia, Egypt, 411522, Al Ismailiyya, 411522, Egypt, , 01 Mar 2021, +20643200789, rec@med.Suez.edu.eg, 25510_24355_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 16/05/2023 I meant that the study was self funded without receiving any grants or funds. The principal investigator, Salah El-Deen El-Ayoubi st., Building 6R, Ismailia, 41511, Egypt, Self Funded,
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 17/05/2023 To include the IPD sharing statement Yes, individual participant data will be available to other researchers Yes, individual participant data will be available to other researchers. All individual participant data were collected during the study after deidentification. Data will be available immediately following publication to any researcher who wishes to access the data. Data will be available indefinitely after publication.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD URL 17/05/2023 To save results url https://medsuezedu-my.sharepoint.com/personal/pgs_000936596_med_suez_edu_eg/Documents/Documents/Results/
Section Name Field Name Date Reason Old Value Updated Value
Reporting Date of the first journal publication 17/05/2023 No change 01 Jan 0001
Section Name Field Name Date Reason Old Value Updated Value
Reporting Results & Publication URL 17/05/2023 Add URL links of the study results https://medsuezedu-my.sharepoint.com/personal/pgs_000936596_med_suez_edu_eg/Documents/Documents/Results/
Section Name Field Name Date Reason Old Value Updated Value
Reporting Link to protocol 17/05/2023 Add link of the study protocol https://drive.google.com/file/d/1c2rKWkPUPl5QtBw8Pm8BSj87DLMuvXun/view?usp=drivesdk
Section Name Field Name Date Reason Old Value Updated Value
Reporting Results Available 17/05/2023 Results are now available through the url link No Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting Result Summary Pdf file1 17/05/2023 To upload results document 25510_18283_1045.pdf