TY - JOUR
T1 - DICE
T2 - Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian cancer resistant to standard treatment—a study protocol for a randomised trial investigating a novel therapy called TAK228
AU - Fiorentino, Francesca
AU - Krell, Jonathan
AU - de la Rosa, Consuelo Nohpal
AU - Webber, Lee
N1 - Funding Information:
The authors would like to acknowledge Meena Reddi, the Clinical Trial Coordinator for the study, who has reviewed the protocol paper prior to submission. FF is the senior statistician and has contributed to and reviewed the relevant statistical sections of the protocol paper. JK is the Chief Investigator and has therefore led protocol development, including contribution to and review of the protocol paper. CNdlR is the study statistician and has led contributions to the relevant statistical sections of the protocol paper, as well as reviewing the protocol paper in full. LW is the corresponding author and operational lead on the study and has led the drafting and revision of the protocol paper as a whole. All authors have read and approved the final manuscript. Industry funding and free provision of TAK228 by Takeda Pharmaceuticals International Co and Calithera Biosciences, Inc. Study funder has advisory role in study design and collection of data and must provide consent for any publication of data as per the contractual agreement with the study sponsor. The Chief Investigator is the custodian of the final trial dataset, which may be shared according to both the contractual agreement with the funder and relevant standard operating procedures.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. Methods: One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up. Discussion: The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial. Trial registration: ClinicalTrials.govNCT03648489. Registered on 27 August 2018.
AB - Background: The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. Methods: One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up. Discussion: The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial. Trial registration: ClinicalTrials.govNCT03648489. Registered on 27 August 2018.
KW - Ovarian cancer
KW - Platinum-resistant
KW - TAK228
KW - Weekly paclitaxel
UR - http://www.scopus.com/inward/record.url?scp=85127692891&partnerID=8YFLogxK
U2 - 10.1186/s13063-022-06201-3
DO - 10.1186/s13063-022-06201-3
M3 - Article
C2 - 35382842
AN - SCOPUS:85127692891
SN - 1745-6215
VL - 23
JO - Trials
JF - Trials
IS - 1
M1 - 261
ER -
