A phase II study of Avelumab + stereotactic ablative body radiosurgery (SABR) for metastatic castration-resistant prostate cancer (mCRPC)
- Conditions
- Metastatic castration-resistant prostate cancer (mCRPC).Cancer - Prostate
- Registration Number
- ACTRN12618000954224
- Lead Sponsor
- Monash Health
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Male
- Target Recruitment
- 25
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess radiographic progression-free survival (rPFS) at 24 weeks in mCRPC patients treated with Avelumab + SABR .<br><br>[The 30-day Safety Follow Up and 3-month Follow-up visit procedures are listed in The Schedule of Events of the protocol. After the end of treatment, each participant will be followed for 30 days for AE monitoring (SAEs will be collected for 90 days after the end of treatment as in the protocol). Participants who discontinue treatment will have post treatment follow-up for disease status until initiating a non-study systemic cancer treatment, withdrawing consent or becoming lost to follow-up. <br><br>24 weeks progression-free survival post treatment]
- Secondary Outcome Measures
Name Time Method