PMID- 34986897
OWN - NLM
STAT- MEDLINE
DCOM- 20220107
LR  - 20231105
IS  - 1745-6215 (Electronic)
IS  - 1745-6215 (Linking)
VI  - 23
IP  - 1
DP  - 2022 Jan 5
TI  - Statistical analysis plan for the Dual mTorc Inhibition in advanCed/recurrent 
      Epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, 
      endometrioid and high-grade serous type, and carcinosarcoma) trial (DICE).
PG  - 13
LID - 10.1186/s13063-021-05669-9 [doi]
LID - 13
AB  - BACKGROUND: Treatment for ovarian cancer includes platinum-based chemotherapy, 
      but many women become resistant to chemotherapy, becoming platinum-resistant. 
      Standard of care for these women is weekly paclitaxel chemotherapy, but cancers 
      can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 
      inhibitor, is an oral therapy that can be added to standard treatment. The DICE 
      trial is a phase II international multicentre, parallel-group, superiority 
      clinical trial with 1:1, open label randomisation which has the aim of 
      investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned 
      sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian 
      cancer. OBJECTIVE: To outline the planned analyses for DICE in a statistical 
      analysis plan (SAP) before database hard lock and the start of analysis. This 
      ensures that bias is minimised during the analysis phase. RESULTS: This SAP 
      provides detailed descriptions of the analysis principles and statistical 
      procedures for analysing primary and secondary outcomes of the trial. The primary 
      outcome is overall progression-free survival (PFS). Secondary outcomes include 
      progression-free survival (PFS) at 24 weeks, overall response rate (ORR), 
      duration of response (DoR), time to progression (TTP), clinical benefit rate 
      (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to 
      Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety 
      and tolerability as assessed by adverse events and the quality-of-life 
      questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description 
      includes significance levels, sensitivity analyses and compliance analysis. 
      DISCUSSION: The DICE trial will determine whether the addition of TAK228 to 
      weekly paclitaxel chemotherapy shows a statistically significant improvement to 
      participant's progression free and overall survival and that the adverse events 
      (AEs) and quality of life (QoL) are not significantly worse than the standard 
      treatment. The study commenced recruitment in September 2018. An interim analysis 
      was performed in early 2021, the results of which advised continuation of the 
      trial. The study recruitment is ongoing and is due to complete by the end of 
      2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT03648489 . Registered on 27 
      August 2018.
CI  - (c) 2021. The Author(s).
FAU - de la Rosa, Consuelo Nohpal
AU  - de la Rosa CN
AD  - Imperial Clinical Trials Unit, School of Public Health, Imperial College London, 
      London, UK.
FAU - Krell, Jonathan
AU  - Krell J
AD  - Department of Surgery and Cancer, Imperial College London, London, UK.
FAU - Day, Emily
AU  - Day E
AD  - Imperial Clinical Trials Unit, School of Public Health, Imperial College London, 
      London, UK.
FAU - Clarke, Aaron
AU  - Clarke A
AD  - Department of Surgery and Cancer, Imperial College London, London, UK.
FAU - Reddi, Meena
AU  - Reddi M
AD  - Department of Surgery and Cancer, Imperial College London, London, UK.
FAU - Webber, Lee
AU  - Webber L
AD  - Department of Surgery and Cancer, Imperial College London, London, UK.
FAU - Fiorentino, Francesca
AU  - Fiorentino F
AUID- ORCID: 0000-0001-9817-6634
AD  - Imperial Clinical Trials Unit, School of Public Health, Imperial College London, 
      London, UK. f.fiorentino@imperial.ac.uk.
AD  - Department of Surgery and Cancer, Imperial College London, London, UK. 
      f.fiorentino@imperial.ac.uk.
AD  - Nightingale-Saunders Clinical Trials & Epidemiology Unit, King's CTU, King's 
      College London, London, UK. f.fiorentino@imperial.ac.uk.
LA  - eng
SI  - ClinicalTrials.gov/NCT03648489
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20220105
PL  - England
TA  - Trials
JT  - Trials
JID - 101263253
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Carcinosarcoma
MH  - Fallopian Tubes
MH  - Female
MH  - Humans
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - *Ovarian Neoplasms/drug therapy
MH  - Paclitaxel/adverse effects
MH  - Quality of Life
PMC - PMC8728702
OTO - NOTNLM
OT  - Ovarian cancer
OT  - Paclitaxel
OT  - Platinum-resistant
OT  - Randomised controlled trial
OT  - Statistical analysis plan
OT  - TAK228
COIS- The authors declare that they have no competing interests.
EDAT- 2022/01/07 06:00
MHDA- 2022/01/08 06:00
PMCR- 2022/01/05
CRDT- 2022/01/06 05:38
PHST- 2021/07/01 00:00 [received]
PHST- 2021/09/29 00:00 [accepted]
PHST- 2022/01/06 05:38 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/01/08 06:00 [medline]
PHST- 2022/01/05 00:00 [pmc-release]
AID - 10.1186/s13063-021-05669-9 [pii]
AID - 5669 [pii]
AID - 10.1186/s13063-021-05669-9 [doi]
PST - epublish
SO  - Trials. 2022 Jan 5;23(1):13. doi: 10.1186/s13063-021-05669-9.