DICE is a randomised study recruiting 126 women over 3 years from hospitals in the UK and Germany. Eligible patients will have tissue based diagnosis of advanced/recurrent ovarian cancer (clear cell, endometrioid or high grade serous or carcinosarcoma), have had chemotherapy before, and be platinum-resistant (the cancer has returned/grown significantly during or within 6 months of platinum-containing chemotherapy).
This study is for women with ovarian cancer that has come back following treatment, and is resistant to platinum chemotherapy. Weekly paclitaxel chemotherapy is standard for these women, but there is a need to provide more effective treatments. TAK228 is an unlicensed oral drug that blocks the PI3K/AKT/mTOR pathway, which is important to the survival and spread of cancer cells. When TAK228 is combined with paclitaxel in the laboratory, the anti-cancer effect of both is increased. The DICE trial will show whether using TAK228 in combination with weekly paclitaxel is more effective at treating the patient population than weekly paclitaxel alone. DICE will also look for 'biomarkers' that measure the activity of the cancer and the effects of treatment. This may help us understand which women might benefit from receiving TAK228 and weekly paclitaxel in future. Randomisation will be to one of 2 groups (63 women in each). Treatment is divided into 4 week 'cycles': Group 1: weekly paclitaxel for 3 weeks followed by 1 week rest each cycle Group 2: weekly paclitaxel (see Group 1) plus TAK228 for 12 days each cycle Women will stop treatment when the cancer grows significantly, there are unacceptable side effects, or the investigator and/or patient decides to stop. Women will be followed up until 6 months after the last patient receiving study treatment stops that treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
134
Please refer to arm/group description
Please refer to arm/group description
Charité Universitätsmedizin Berlin
Berlin, Germany
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, Germany
KEM Kliniken Essen-Mitte
Essen, Germany
Furness General Hospital
Barrow in Furness, Cumbria, United Kingdom
St George's University Hospitals NHS Foundation Trust
London, Greater London, United Kingdom
The Royal Marsden NHS Foundation Trust
London, Greater London, United Kingdom
Imperial College Healthcare NHS Trust
London, Greater London, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton, Greater London, United Kingdom
The Christie NHS Foundation Trust
Manchester, Greater Manchester, United Kingdom
Royal Lancaster Infirmary
Lancaster, Lancashire, United Kingdom
...and 5 more locations
Progression Free Survival (PFS)
PFS (as assessed by RECIST v1.1), defined as time from study entry to first evidence of disease progression or death due to any cause
Time frame: 12 months
Progression Free Survival (PFS) at 24 weeks
PFS (as assessed by RECIST v1.1) at 24 weeks, defined as time from study entry to first evidence of disease progression or death due to any cause
Time frame: 6 months
Overall Response Rate (ORR)
ORR (as assessed by RECIST v1.1) defined by complete response (CR) or partial response (PR)
Time frame: 12 months
Duration of Response (DOR)
DOR defined as time from study entry to change in response from CR or PR to stable disease (SD) or progressive disease (PD) (as assessed by RECIST v1.1)
Time frame: 12 months
Time to Progression (TTP)
TTP defined as time from study entry to first evidence of disease progression or death due to any cause
Time frame: 12 months
Clinical Benefit Rate (CBR) at 4 months
TTP defined as time from study entry to first evidence of disease progression or death due to any cause
Time frame: 4 months
Response according to Gynecologic Cancer Intergroup (GCIG) CA125 criteria
A response according to CA125 has occurred if there is at least a 50% reduction in CA125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA125 only if they have a pretreatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment
Time frame: 12 months
Overall Survival (OS)
OS defined as time from study entry to death due to any cause or to study termination
Time frame: 12 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
The number of patients experiencing 1 or more AEs will be summarised by the event name, relationship to study treatment and severity
Time frame: 12 months
Change from baseline quality of life (QOL) as assessed by EORTC QLQ-C30 questionnaire Global Health Status Domain
EORTC QLQ-C30 is used to assess the overall quality of life in cancer patients. It consists of 30 questions and 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement
Time frame: 12 months
Change from baseline QOL as assessed by EORTC QLQ-OV28 questionnaire
EORTC QLQ-OV28 is used to assess the overall health-related quality of life in patients with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste. Questions use a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment
Time frame: 12 months
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