Ignite Creation Date:
2025-12-25 @ 4:14 AM
Ignite Modification Date:
2026-03-09 @ 1:17 PM
Study NCT ID:
NCT06838520
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-02-20
First Post:
2025-02-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of ADT and ARPI on Bone Loss of Patients with Prostate Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011471', 'term': 'Prostatic Neoplasms'}, {'id': 'D000230', 'term': 'Adenocarcinoma'}], 'ancestors': [{'id': 'D005834', 'term': 'Genital Neoplasms, Male'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D005832', 'term': 'Genital Diseases, Male'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D011469', 'term': 'Prostatic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-04-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-02', 'completionDateStruct': {'date': '2030-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-02-17', 'studyFirstSubmitDate': '2025-02-03', 'studyFirstSubmitQcDate': '2025-02-17', 'lastUpdatePostDateStruct': {'date': '2025-02-20', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-02-20', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2030-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'BMD loss measured at lumbar spine', 'timeFrame': 'every 6 months, up to 2 years', 'description': 'Measured by bone densitometry'}, {'measure': 'BMD loss measured at hip', 'timeFrame': 'every 6 months, up to 2 years', 'description': 'Measured by bone densitometry'}], 'secondaryOutcomes': [{'measure': 'trabecular bone score (TBS) changes', 'timeFrame': 'every 6 months, up to 2 years', 'description': 'Measured by bone densitometry'}, {'measure': 'major osteoporotic fracture risk', 'timeFrame': '24 months', 'description': 'Estimated by Fracture Risk Assessment Tool (FRAX®)'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['prostate cancer', 'ADT', 'ARPI', 'bone health'], 'conditions': ['Prostate Cancer (Adenocarcinoma)']}, 'referencesModule': {'references': [{'pmid': '30321335', 'type': 'BACKGROUND', 'citation': 'Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, Bilezikian J. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr Rev. 2019 Aug 1;40(4):1109-1151. doi: 10.1210/er.2018-00126.'}, {'pmid': '32880851', 'type': 'BACKGROUND', 'citation': "D'Andrea S, Martorella A, Coccia F, Castellini C, Minaldi E, Totaro M, Parisi A, Francavilla F, Francavilla S, Barbonetti A. Relationship of Vitamin D status with testosterone levels: a systematic review and meta-analysis. Endocrine. 2021 Apr;72(1):49-61. doi: 10.1007/s12020-020-02482-3. Epub 2020 Sep 3."}, {'pmid': '30929797', 'type': 'BACKGROUND', 'citation': 'Feng W, Guo J, Li M. RANKL-independent modulation of osteoclastogenesis. J Oral Biosci. 2019 Mar;61(1):16-21. doi: 10.1016/j.job.2019.01.001. Epub 2019 Jan 11.'}, {'pmid': '34127184', 'type': 'BACKGROUND', 'citation': 'Kokorovic A, So AI, Serag H, French C, Hamilton RJ, Izard JP, Nayak JG, Pouliot F, Saad F, Shayegan B, Aprikian A, Rendon RA. Canadian Urological Association guideline on androgen deprivation therapy: Adverse events and management strategies. Can Urol Assoc J. 2021 Jun;15(6):E307-E322. doi: 10.5489/cuaj.7355. No abstract available.'}, {'pmid': '30286662', 'type': 'BACKGROUND', 'citation': 'Bhowmik D, Song X, Intorcia M, Gray S, Shi N. Examination of burden of skeletal-related events in patients naive to denosumab and intravenous bisphosphonate therapy in bone metastases from solid tumors population. Curr Med Res Opin. 2019 Mar;35(3):513-523. doi: 10.1080/03007995.2018.1532884. Epub 2018 Nov 20.'}]}, 'descriptionModule': {'briefSummary': 'This study aims to assess the impact of Androgen Deprivation Therapy (ADT) and Androgen Receptor Pathway Inhibitors (ARPI) on bone quality in patients with prostate cancer. Patients undergoing ADT for prostate cancer often experience adverse effects such as decreased bone density and increased fracture risk. While ARPIs are emerging as novel therapeutic agents, their effects on bone quality remain unclear. This study will compare patients receiving combined ADT and ARPI therapy with those receiving ADT alone, evaluating changes in bone density, bone microarchitecture, and bone metabolic markers. The findings will help optimize treatment strategies for prostate cancer patients, reduce the risk of osteoporosis, and improve overall quality of life.', 'detailedDescription': 'Prostate cancer is the second most common malignancy in men worldwide and ranks fifth in cancer mortality among men. In developed countries in Europe and America, it has the highest incidence rate. In recent years, with the development of the social economy, increased life expectancy, changes in lifestyle, and improvements in the level of medical and health care, the incidence of prostate cancer in China is gradually rising, posing a serious threat to the life safety of men. In China, more than half of the patients with newly diagnosed prostate cancer have advanced metastatic disease. The skeleton is the most common site of metastasis in these patients. Metastatic lesions may cause pathological fractures and spinal cord compression. Patients with extensive bone metastasis are prone to fatigue, weight loss, anemia, and in severe cases, even systemic organ failure. Hormonal therapy based on ADT remains the main treatment for advanced prostate cancer, with the goal of reducing or eliminating the promoting effect of androgens on cancer cell growth.\n\nWhile ADT treatment benefits patients with metastatic prostate cancer, it also leads to numerous side effects, such as cardiovascular diseases, changes in body composition, decreased bone mineral density (BMD), hot flashes, gynecomastia, cognitive decline, fatigue, anemia, and sexual dysfunction. ADT treatment can affect the number and function of osteoblasts and osteoclasts through various pathways, disrupting the balance of bone remodeling and leading to cancer treatment-induced bone loss. Under normal conditions, testosterone can be converted to estradiol via aromatase and bind to the estrogen receptors on the surface of osteoclasts, indirectly regulating these cells. With increasing age, the bioactivity of both testosterone and estrogen declines in normal men, resulting in low-turnover bone metabolic changes and a bone loss rate of 0.5% to 1% per year. In patients undergoing ADT, the levels of testosterone and estrogen decrease more significantly, and the number of osteoclasts increases markedly. Moreover, ADT treatment can reduce muscle mass and increase fat, leading to sarcopenic obesity, which is accompanied by chronic low-grade inflammation throughout the body and disrupts bone homeostasis. ADT may also lower the levels of circulating vitamin D, which not only affects bone mineralization but also has adverse effects on skeletal muscle and prostate cancer itself. Studies have shown that after 12 months of ADT treatment, the median lumbar spine BMD in patients decreased by an average of 3.6%, higher than that in untreated elderly men (0.5% to 1%). The BLADE study (NCT03202381) confirmed that long-term ADT treatment with either Gonadotropin-releasing hormone (GnRH) receptor agonists or antagonists significantly reduces bone quality. In fact, bone loss caused by ADT treatment can also lead to skeletal-related events (SREs), represented by pathological fractures, bone radiotherapy, bone surgery, and spinal cord compression.\n\nARPIs play a crucial role in the treatment of prostate cancer. Prostate cancer cells often rely on androgens for growth, and ARPIs work by blocking the androgen receptor pathway, thereby inhibiting the proliferation of cancer cells. These inhibitors, such as abiraterone, enzalutamide, and apalutamide, have significantly improved outcomes for patients with advanced prostate cancer, including those with metastatic castration-resistant prostate cancer (mCRPC). By reducing the levels of androgens or blocking their effects, ARPIs may also negatively impact bone quality in patients with prostate cancer. These agents, by reducing androgen levels, may lead to decreased BMD and increased fracture risk.\n\nThe impact of combining ADT with ARPIs on bone quality remains unclear. While clinical trial data on ARPIs in nonmetastatic castration-resistant prostate cancer (nmCRPC) have shown mixed results regarding bone health. Further research is needed to fully understand the combined effects of ADT and ARPIs on bone quality. It is essential to gain a deeper understanding of the patterns of osteoporosis to provide most effective bone-protective therapies to prevent the occurrence of SREs.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'This study will include male patients with locally advanced or metastatic hormone-sensitive prostate cancer (mHSPC) in mainland China. All patients must have visited the urology or oncology outpatient departments of a tertiary hospital and have a pathological confirmation of the disease.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age ≥ 18 years, male gender;\n2. Histologically or cytologically confirmed prostate cancer;\n3. Clinical stage of metastatic hormone-sensitive prostate cancer (mHSPC);\n4. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2;\n5. Life expectancy ≥ 12 months;\n6. Willing and able to provide written informed consent.\n\nExclusion Criteria:\n\n1. Suffering from double primary malignancies.\n2. Having previously received androgen deprivation therapy (ADT) or other pharmacological treatments (e.g., denosumab, bisphosphonates, or corticosteroids).\n3. Having osteoporosis at baseline (T-score ≤ -2.5).\n4. Having known bone diseases.\n5. Having spinal metastases confirmed by imaging (e.g., ECT, MRI, CT, or PSMA PET-CT).\n6. Having poor general condition (i.e., ECOG ≥ 4).\n7. Having a life expectancy of less than 12 months.\n8. Having elevated serum PSA levels (≥4 ng/dL) or testosterone levels (≥50 ng/dL) after 6 months of ADT.'}, 'identificationModule': {'nctId': 'NCT06838520', 'briefTitle': 'Effect of ADT and ARPI on Bone Loss of Patients with Prostate Cancer', 'organization': {'class': 'OTHER', 'fullName': 'The First Affiliated Hospital with Nanjing Medical University'}, 'officialTitle': 'A Prospective Study on the Impact of Androgen Deprivation Therapy (ADT) and Androgen Receptor Pathway Inhibitors (ARPI) on Bone Loss in Prostate Cancer Patients', 'orgStudyIdInfo': {'id': '2024-SR-999'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Group A: ADT alone', 'description': 'Men with locally advanced prostate cancer or metastatic hormone-sensitive prostate cancer, about to start treatment.\n\nADT including LHRH agonist and antagonist.', 'interventionNames': ['Other: Bone health assessment']}, {'label': 'Group B: ADT + ARPIs', 'description': 'Men with locally advanced prostate cancer or metastatic hormone-sensitive prostate cancer, about to start treatment.\n\nADT including LHRH agonist and antagonist. ARPIs including Abiraterone Acetate, Enzalutamide, Apalutamide, Darolutamide or Rezvilutamide.', 'interventionNames': ['Other: Bone health assessment']}], 'interventions': [{'name': 'Bone health assessment', 'type': 'OTHER', 'description': 'Assessments of physical function, DXA scan', 'armGroupLabels': ['Group A: ADT alone', 'Group B: ADT + ARPIs']}]}, 'contactsLocationsModule': {'locations': [{'zip': '213004', 'city': 'Changzhou', 'state': 'Jiangsu', 'country': 'China', 'contacts': [{'name': 'Dong Xue, MD', 'role': 'CONTACT', 'email': 'xuedongdx@163.com', 'phone': '+8615251840611'}], 'facility': 'The Third Affiliated Hospital of Soochow University', 'geoPoint': {'lat': 31.77359, 'lon': 119.95401}}, {'zip': '210009', 'city': 'Nanjing', 'state': 'Jiangsu', 'country': 'China', 'contacts': [{'name': 'Bianjiang Liu, MD', 'role': 'CONTACT', 'email': 'bjliu@njmu.edu.cn', 'phone': '+8613851493417'}], 'facility': 'The First Affiliated Hospital of Nanjing Medical University', 'geoPoint': {'lat': 32.06167, 'lon': 118.77778}}, {'zip': '215006', 'city': 'Suzhou', 'state': 'Jiangsu', 'country': 'China', 'contacts': [{'name': 'Xuedong Wei, MD', 'role': 'CONTACT', 'email': 'wxd0422@163.com', 'phone': '+8615251840611'}], 'facility': 'The First Affiliated Hospital of Soochow University', 'geoPoint': {'lat': 31.30408, 'lon': 120.59538}}, {'zip': '225009', 'city': 'Yangzhou', 'state': 'Jiangsu', 'country': 'China', 'contacts': [{'name': 'Xuefei Ding', 'role': 'CONTACT', 'email': 'xuefeid@126.com', 'phone': '+8615251840611'}], 'facility': "Northern Jiangsu People's Hospital", 'geoPoint': {'lat': 32.39722, 'lon': 119.43583}}], 'centralContacts': [{'name': 'Bianjiang Liu, MD', 'role': 'CONTACT', 'email': 'bjliu@njmu.edu.cn', 'phone': '+8613851493417'}, {'name': 'Ruizhe Zhao, MD', 'role': 'CONTACT', 'email': 'drzrzurology@njmu.edu.cn', 'phone': '+8615251840611'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'The First Affiliated Hospital with Nanjing Medical University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Bianjiang Liu', 'investigatorAffiliation': 'The First Affiliated Hospital with Nanjing Medical University'}}}}