scholarly journals Protocol Amendment

2020 ◽  
Author(s):  
Keyword(s):  
Protocol Amendment

ICEPAC: A phase II multicenter study of avelumab combined with stereotactic ablative body radiotherapy (SABR) in metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 86-86
Author(s):  
Arun Azad ◽  
Lavinia Anne Spain ◽  
Angelyn Anton ◽  
Chun Loo Gan ◽  
Linda Garrett ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Disease Control ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Checkpoint Inhibitors ◽  
Disease Assessment ◽  
Castration Resistant Prostate Cancer ◽  
Protocol Amendment ◽  
Stereotactic Ablative Body Radiotherapy ◽  
Taxane Chemotherapy

86 Background: Studies investigating immune checkpoint inhibitors (ICI) in mCRPC have produced modest results. Radiation therapy may be synergistic with ICIs. We hypothesised that SABR would enhance anti-tumour activity of PD-L1 inhibitor avelumab in patients (pts) with progressive mCRPC. Methods: This phase II, single arm, multicentre study enrolled mCRPC pts following progression on ≥1 novel androgen receptor-directed therapy. Up to two lines of prior taxane chemotherapy were permitted. Pts received avelumab 10mg/kg IV q2weeks for a total of 24 weeks (12 cycles). A single fraction of 20Gy SABR was administered to 1-2 disease sites within five days prior to first and second doses of avelumab. Primary endpoint was disease control rate (DCR); secondary endpoints were PSA response (PSA50), overall response rate (ORR), radiographic progression-free survival (rPFS), overall survival (OS) and safety. Radiographic disease assessment (CT and bone scintigraphy) was performed after cycles 6 and 12 of avelumab treatment. Following enrolment of 14 pts, a protocol amendment allowed avelumab beyond 12 cycles in pts with disease control at 24 weeks. Results: Thirty-one pts were enrolled, with 30 evaluable for the primary endpoint. Median follow-up was 18 months (mo). Pt characteristics: median age 71 years (IQR 64-75), bone-only disease 42%, visceral disease 16%, prior taxane chemotherapy 84%, treatment with both abiraterone and enzalutamide 13%. Seventy metastatic sites received SABR, most frequently to bone (90%) and soft tissue (29%) disease. Avelumab was given as second-line, third-line and fourth- or greater line systemic therapy in 29%, 42% and 29% of pts, respectively. Median cycles of avelumab administered was 9 (IQR 5-13). DCR (95% CI) was 50% (31-69) and 60% (32-84) in all-comers and soft tissue disease subgroup, respectively. Following protocol amendment, 7/17 pts (41%) received avelumab beyond 12 cycles. Incidence of grade 3-4 treatment-related AEs was 16% (no grade 5 events), with three pts requiring oral/IV corticosteroid therapy. Conclusions: Avelumab with SABR demonstrated durable disease control in treatment-refractory mCRPC with an acceptable toxicity profile. This combination warrants further investigation. Clinical trial information: ACTRN12618000954224. [Table: see text]

scholarly journals Efficacy and Safety of Degludec Compared to Glargine 300 Units/mL in Insulin-Experienced Patients With Type 2 Diabetes: Trial Protocol Amendment (NCT03078478)

2019 ◽  
Vol 13 (3) ◽  
pp. 498-506 ◽  
Author(s):  
Athena Philis-Tsimikas ◽  
Irene Stratton ◽  
Lone Nørgård Troelsen ◽  
Britta Anker Bak ◽  
Lawrence A. Leiter
Keyword(s):  
Patient Safety ◽  
Blood Glucose ◽  
Data Collection ◽  
Treatment Period ◽  
Collection System ◽  
Data Collection System ◽  
Protocol Amendment ◽  
Trial Conduct ◽  
Glucose Meter ◽  
Blood Glucose Meter

Background: A head-to-head trial (NCT03078478) between insulin degludec and insulin glargine U300 with the primary objective of comparing the risk of hypoglycemia is being conducted. During trial conduct, safety concerns related to the glycemic data collection system led to a postinitiation protocol amendment, described here. Methods: This randomized (1:1), open-label, treat-to-target, multinational trial was initiated in March 2017 with a planned treatment period of 52 weeks (16 weeks titration + 36 weeks maintenance). Overall, ~1600 insulin-experienced patients at risk of developing hypoglycemia based on predefined risk factors were included. The protocol amendment implemented in February 2018 resulted in assuring patient safety and an extension of the total treatment period up to 88 weeks (16 weeks titration + variable maintenance 1 + 36 weeks maintenance 2). The original glycemic data collection system (MyGlucoHealth blood glucose meter + electronic diary) was discontinued because of safety concerns and replaced with an Abbott blood glucose meter and paper diary to collect self-measured blood glucose and hypoglycemic episodes. The primary endpoint of number of severe or blood-glucose confirmed symptomatic hypoglycemic episodes will be evaluated with the same analysis duration and statistical methods as the original protocol. Only relevant changes were implemented to maintain patient safety while permitting evaluation of the scientific objectives of the trial. Conclusions: These observations highlight the importance of safety surveillance during trial conduct despite the use of currently marketed glucose monitoring devices. The prompt protocol amendment and ensuing actions ensured that the scientific integrity of the trial was not compromised.

Sign in / Sign up

Export Citation Format

Share Document