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Trial registered on ANZCTR


Registration number
ACTRN12618000954224
Ethics application status
Approved
Date submitted
18/05/2018
Date registered
6/06/2018
Date last updated
27/11/2018
Date data sharing statement initially provided
27/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A phase II study of Avelumab + stereotactic ablative body radiosurgery (SABR) for metastatic castration-resistant prostate cancer (mCRPC)
Scientific title
A phase II study of Avelumab + stereotactic ablative body radiosurgery (SABR) for metastatic castration-resistant prostate cancer (mCRPC). To assess radiographic progression-free survival (rPFS).
Secondary ID [1] 294337 0
MS100070-0082
Universal Trial Number (UTN)
Trial acronym
ICE-PAC
Linked study record
NA

Health condition
Health condition(s) or problem(s) studied:
Metastatic castration-resistant prostate cancer (mCRPC). 307057 0
Condition category
Condition code
Cancer 306168 306168 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 300642 0
Treatment: Devices
Intervention code [2] 300822 0
Treatment: Drugs
Intervention code [3] 301399 0
Treatment: Other
Comparator / control treatment
NA
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305177 0
To assess radiographic progression-free survival (rPFS) at 24 weeks in mCRPC patients treated with Avelumab + SABR .

Timepoint [1] 305177 0
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.

24 weeks progression-free survival post treatment
Secondary outcome [1] 344404 0
• To assess rPFS in non-irradiated metastases by using data-linkage to medical records, computed tomography (CT) scan, MRI, study-specific questionnaire,

Timepoint [1] 344404 0
30 day safety follow-up and 6 month overall survival from End of Study treatment day
Secondary outcome [2] 347570 0
To assess time to PSA progression (PCWG2 criteria)
Timepoint [2] 347570 0
30 day safety follow-up and 6 month overall survival from End of Study treatment day
Secondary outcome [3] 347571 0
To assess objective response rate (RECIST for soft tissue lesions on CT)
Timepoint [3] 347571 0
30 day safety follow-up and 6 month overall survival from End of Study treatment day
Secondary outcome [4] 347572 0
To assess OS 6 months after last patient is enrolled using data-linkage to medical records, telephone follow-up, audit of national deaths registry, study-specific questionnaire
Timepoint [4] 347572 0
30 day safety follow-up and 6 month overall survival from End of Study treatment day
Secondary outcome [5] 347573 0
To assess safety and toxicity of treatment using serum assay, study-specific questionnaire, 100mm visual analogue scale, Participant grading their experience of toxicity graded on a 100mm visual analogue scale, participants providing a subjective opinion of safety on a 100mm visual analogue scale,
Timepoint [5] 347573 0
30 day safety follow-up and 6 month overall survival from End of Study treatment day

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
NA
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
NA
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Simon’s two stage design will be employed

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 10580 0
Box Hill Hospital - Box Hill
Recruitment hospital [2] 10581 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 22064 0
3168 - Clayton
Recruitment postcode(s) [2] 22065 0
3128 - Box Hill

Funding & Sponsors
Funding source category [1] 298980 0
Commercial sector/Industry
Name [1] 298980 0
Merck KGaA
Address [1] 298980 0
Frankfurter Str. 250, 64283 Darmstadt
Country [1] 298980 0
Germany
Funding source category [2] 299146 0
Hospital
Name [2] 299146 0
Monash Health
Address [2] 299146 0
246 Clayton Road, Clayton VIC 3168
Country [2] 299146 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Road, Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 298406 0
None
Name [1] 298406 0
Address [1] 298406 0
Country [1] 298406 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299910 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 299910 0
246 Clayton Road, Clayton VIC 3168
Ethics committee country [1] 299910 0
Australia
Date submitted for ethics approval [1] 299910 0
26/06/2017
Approval date [1] 299910 0
27/09/2017
Ethics approval number [1] 299910 0

Summary
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.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 81958 0
Dr Edmond Kwan
Address 81958 0
Monash Health, 246 Clayton Road, Clayton VIC 3168
Country 81958 0
Australia
Phone 81958 0
+61 3 8572 2392
Fax 81958 0
Email 81958 0
edmond.kwan@monash.edu
Contact person for public queries
Name 81959 0
Miss Sabah Saad
Address 81959 0
Monash Health, 246 Clayton Road, Clayton VIC 3168
Country 81959 0
Australia
Phone 81959 0
+61 3 8572 2392
Fax 81959 0
Email 81959 0
sabah.saad@monashhealth.org
Contact person for scientific queries
Name 81960 0
Dr Edmond Kwan
Address 81960 0
Monash Health, 246 Clayton Road, Clayton VIC 3168
Country 81960 0
Australia
Phone 81960 0
+61 3 8572 2392
Fax 81960 0
Email 81960 0
edmond.kwan@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results