None listed
Conditions
Brief summary
The purpose of this study is to investigate the safety and efficacy of stereotactic ablative body radiotherapy (SABR) plus Avelumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Who is it for? You may be eligible for this study if you are an adult with metastatic castration-resistant prostate cancer (mCRPC) and have a predicted life expectancy of at least 6 months. Study details This project will investigate the combination of SABR and Avelumab for metastatic castration resistant prostate cancer (mCRPC). SABR is a noninvasive, high precision radiotherapy technique. The high precision of SABR allows a high dose of radiation to be delivered to the target areas with minimal toxicity to the surrounding areas. Avelumab is a monoclonal antibody that works against a protein called PD1 on the surface of the cancer cells. It is thought that cancer cells with increased levels of PD1 avoid detection by the body’s immune system. In this study, we hypothesise that combining Avelumab with standard therapy high dose precision radiotherapy (SABR) may enhance the antitumour efficacy of Avelumab in mCRPC. This study will evaluate the patient survival, tumour regrowth and side effects with this combined treatment in patients with mCRPC.
Interventions
SABR (stereotactic ablative body radiosurgery) treatment . SABR will be delivered as a single fraction of 20 Gy to 1-2 metastases (bone and/or lymph node) with the location of sites selected at the discretion of the treating radiation oncologist. This will be followed by Avelumab commencing within 5 days +/- 3 days of SABR. Avelumab will be administered at 10 mg/kg intravenous (IV) every 2 weeks (Q2W). A second course of treatment with SABR to 1-2 different metastases will be delivered 5 days +/
SABR (stereotactic ablative body radiosurgery) treatment . SABR will be delivered as a single fraction of 20 Gy to 1-2 metastases (bone and/or lymph node) with the location of sites selected at the discretion of the treating radiation oncologist. This will be followed by Avelumab commencing within 5 days +/- 3 days of SABR. Avelumab will be administered at 10 mg/kg intravenous (IV) every 2 weeks (Q2W). A second course of treatment with SABR to 1-2 different metastases will be delivered 5 days +/-3 days after cycle 1 of Avelumab. The length of an Avelumab cycle is 14 days. All radiotherapy courses should be completed in a single session. The sites treated with radiotherapy should ideally be inclusive of both a bone and a lymph node metastasis.
Sponsors
Monash Health
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age. 2. Willing and able to provide informed written consent. 3. Life expectancy of at least 6 months. 4. Adenocarcinoma of the prostate diagnosed histologically without small cell differentiation. 5. Prior surgical orchiectomy or maintained on luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy 6. Prior treatment with 1 of the following agents: CYP17 inhibitors (including abiraterone acetate (ABI), TAK-700, TOK-001 and ketoconazole), enzalutamide or other experimental anti-androgens (e.g. ARN-509, TOK-001). 7. Prior treatment with up to 1 line of systemic chemotherapy for mCRPC is permitted. 8. Evidence of biochemical or imaging progression in the setting of surgical or medical castration. PD for study entry is defined by one of the following three criteria: a. PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of 1 week between each measurement. b. Soft tissue or visceral disease progression as per RECIST 1.1 criteria c. Bone progression: 2 new lesions on bone scan. 9. Radiographic evidence of metastatic disease documented with bone scan or CT scan. Patients with any number of metastatic sites are permitted to enrol. 10. Adequate organ function laboratory values: a. Absolute neutrophil count (ANC) at 1.5 x 109/L b. Platelets at 100 x 109/L c. Hemoglobin at 9 g/dL d. Creatinine at 1.5 X upper limit of normal (ULN) OR at 60 mL/min calculated creatinine clearance for subject with creatinine levels greater than 1.5 X ULN e. Serum total bilirubin at 1.5 X ULN OR direct bilirubin at ULN for participants with total bilirubin levels greater than 1.5 ULN f. Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) at 2.5 X ULN OR at 5 X ULN for participants with liver metastases g. International normalised ratio (INR)/activated partial prothrombin time (aPTT) at 1.5 X ULN unless subject is receiving anticoagulant therapy as long as prothrombin time (PT) or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants. 11. Eastern cooperative oncology group (ECOG) performance status 0-1. 12. Be willing and able to comply with all study requirements, including treatment, attending assessments and follow-up. 13. Participants should agree to use a highly efficient method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion criteria
1. Subjects for whom urgent treatment with cytotoxic chemotherapy is indicated (e.g., symptomatic metastases). 2. Subjects with active, known or suspected autoimmune disease except type I diabetes mellitus, hypothyroidism only requiring hormone replacement and skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment. 3. Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization. Use of inhaled, intranasal, and topical steroids is acceptable. 4. Prior therapy with anti- PD-1, anti- PD-L1/L2, anti-CD137, or anti-Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways 5. Has had previous high dose radiotherapy (biological equivalent of 30Gy in 10 fractions) to an area to be treated, which includes vertebral bodies 6. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study 7. Prior organ transplantation including allogenic stem-cell transplantation 8. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade 3) 9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (less than 6 months prior to enrollment), myocardial infarction (less than 6 months prior to enrollment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication 10. Initiation or discontinuation of bisphosphonates or denosumab within the previous 28 days. 11. Brain metastases or active epidural disease. 12. Active concurrent malignancy (with the exception of non-melanomatous skin cancer or other superficial cancers not requiring treatment e.g. non-muscle invasive bladder cancer). 13. Evidence of interstitial lung disease or active, non-infectious pneumonitis. 14. Known human immunodeficiency virus (HIV) or active Hepatitis B or C. 15. Has received a live vaccine within 30 days of registration. 16. Has a known history of active TB (Bacillus Tuberculosis). 17. Has had prior chemotherapy, targeted small molecule therapy, radiation therapy or radioisotopes (such as Strontium-89 or Radium-223) 28 days prior to starting study drug 18. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade greater than 1); however, alopecia, sensory neuropathy Grade 2, or other Grade 2 not constituting a safety risk based on investigator’s judgment are acceptable 19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study. 20. Is expecting to father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
Outcome results
None listed