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Ovarian CancerPhase 2DICENCT03648489

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)

A Phase 2 study testing Paclitaxel and TAK228 in people with Ovarian Cancer and Ovarian Neoplasms, run by Imperial College London at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Paclitaxel and TAK228
Could I receive a placebo?
No, everyone receives an active treatment
How many people
134 participants
Where
15 sitesin 2 countries
Study dates
21 Sep 2018to 30 Nov 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed and dated written informed consent prior to admission to the study and initiation of any study procedures in accordance with ICH-GCP guidelines and to the local legislation
  • Females ≥ 18 years of age
  • Pathological diagnosis of ovarian, fallopian tube or primary peritoneal cancer, of clear cell, endometrioid or high grade serous subtype or carcinosarcoma. Local tumour board/MDT histological review is required and in mixed tumours more than 50% endometrioid, clear cell or high grade serous elements are required to define the predominant histology
  • Platinum-resistant (recurrence within 6 months of platinum treatment), or platinum refractory disease (recurrence during platinum treatment), patients having received at least one prior line of chemotherapy. Carboplatin and weekly paclitaxel are permitted as first line therapy and/or as therapy for recurrent platinum sensitive disease i.e. prior to platinum resistant relapse
  • Measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 by CT or MRI
  • Fresh tumour biopsy during screening is compulsory if judged technically feasible by radiologist, unless the local site is unable to collect the sample due to COVID-19 capacity restrictions
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  • Patients with a history of brain metastasis are eligible as long as all the following criteria are met: brain metastases must have been treated, have no evidence of progression or haemorrhage after treatment, have been off dexamethasone for 4 weeks prior to first study treatment, and no ongoing requirement for dexamethasone or anti-epileptic drugs
  • Available blocks for immunohistochemistry (IHC) and tissue microarray (TMA) or, if no block is available, 20 ordinary unstained slides (5µm sections) will be acceptable
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • Adequate organ and bone marrow function
  • Female patients who are postmenopausal for ≥ 1 year before the screening visit OR are surgically sterile OR if of childbearing potential, patient agrees to practice 1 highly effective and 1 additional effective method of contraception or true abstinence from informed consent to 90 days after the last dose of study treatment
  • For women of child-bearing potential, negative blood serum pregnancy test within 14 days prior to the first study treatment
  • Able to swallow oral medication

Who cannot join

  • Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, mTORC1/2 inhibitors or mTORC1 inhibitors
  • Prior weekly single agent paclitaxel
  • Known allergy to paclitaxel and/or any excipients of investigational medicinal products that, in the investigator's opinion, precludes study treatment on clinical and/or safety grounds
  • Treatment with strong inhibitor/s and/or inducer/s of cytochrome P450 (CYP) 3A4 or CYP2C8 within 7 days of study treatment
  • Central nervous system (CNS) metastasis, for patients who have brain metastases, they will be eligible if their brain metastases must have been treated, have no evidence of progression or haemorrhage after treatment, have been off dexamethasone for 4 weeks prior to first study drug administration, and no ongoing requirement for dexamethasone or anti-epileptic drugs
  • Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study
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  • Known human immunodeficiency virus infection
  • Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
  • German sites only: Unable to be regularly followed up for any reason (geographic, familiar, social, psychological, housed in an institution e.g. prison because of a court agreement or administrative order)
  • German sites only: Subjects that are dependent on the sponsor (and/or contracted body e.g. CRO) or investigational site as well as on the investigator
  • Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study treatment, or previously diagnosed with another malignancy and evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Breast feeding or pregnant
  • Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of TAK228. In addition, patients with enteric small bowel stomata are also excluded
  • Treatment with any investigational products, chemotherapy or radiotherapy within 28 days, or major surgery within 21 days of study treatment
  • History of any of the following within the last 6 months before administration of the first dose of study treatment:
  • Ischemic myocardial event, including angina requiring therapy and artery revascularisation procedures
  • Ischemic cerebrovascular event, including transient ischemic attack and artery revascularisation procedures
  • Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
  • Placement of a pacemaker for control of rhythm
  • New York Heart Association (NYHA) Class III or IV heart failure
  • Pulmonary embolism
  • Significant active cardiovascular or pulmonary disease including:
  • Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg). Use of anti-hypertensive agents to control hypertension before first dose of study treatment is allowed.
  • Pulmonary hypertension
  • Uncontrolled asthma or O2 saturation < 90% by arterial blood gas analysis or pulse oximetry on room air
  • Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement
  • Medically significant (symptomatic) bradycardia
  • History of arrhythmia requiring an implantable cardiac defibrillator
  • Baseline prolongation of the rate-corrected QT interval (QTc) e.g. repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or additional risk factors for torsades de pointes (e.g. hypokalaemia, family history of long QT syndrome) and patients who use concomitant medications that prolong the QT/QTc interval
  • Patients receiving systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study treatment
  • Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within 7 days before receiving the first dose of study treatment
  • Poorly controlled diabetes mellitus defined as glycosylated haemoglobin (HbA1c) > 7%; patients with a history of transient glucose intolerance due to corticosteroid administration may be enrolled in this study if all other inclusion/exclusion criteria are met

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United Kingdom12 sites

  • Furness General Hospital

    Barrow in Furness, Cumbria, LA14 4LF

  • Royal Lancaster Infirmary

    Lancaster, Lancashire, LA1 4RP

  • St George's University Hospitals NHS Foundation Trust

    London, Greater London, SW17 0QT

  • The Royal Marsden NHS Foundation Trust

    London, Greater London, SW3 6JJ

  • Imperial College Healthcare NHS Trust

    London, Greater London, W12 0HS

  • The Christie NHS Foundation Trust

    Manchester, Greater Manchester, M20 4BX

  • Mount Vernon Cancer Centre

    Northwood, Middlesex, HA6 2RN

  • Nottingham University Hospitals NHS Trust

    Nottingham, Nottinghamshire, NG5 1PB

  • Churchill Hospital

    Oxford

  • Weston Park Hospital

    Sheffield

  • Southampton General Hospital

    Southampton

  • The Royal Marsden NHS Foundation Trust

    Sutton, Greater London, SM2 5PT

Other trials in United Kingdom

Germany3 sites

  • Charité Universitätsmedizin Berlin

    Berlin

  • Universitätsklinikum Carl Gustav Carus Dresden

    Dresden

  • KEM Kliniken Essen-Mitte

    Essen

Other trials in Germany

About this study

Official title: An International Multi-centre Randomised Phase II Study to Assess the Efficacy of TAK228 in Combination With Intravenous Weekly Paclitaxel Compared With Weekly Paclitaxel Alone in Women With Advanced/Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer (of Clear Cell, Endometrioid and High Grade Serous Type, and Carcinosarcoma)

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).

Read the detailed description

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.

Being tested
Paclitaxel, TAK228
Keywords
TAK228, TAK-228, Paclitaxel, Ovarian cancer, Platinum resistant
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PaclitaxelDrug

    Please refer to arm/group description

  • TAK228Drug

    Please refer to arm/group description

Study groups in NCT03648489
Study groupRoleWhat they receive
Arm 1: Weekly paclitaxel aloneActive comparatorPaclitaxel, concentrate for solution for infusion 80mg per metre squared on day 1, 8 and 15 of a 28 day cycle. Cycles continue until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria
Receives: Drug: Paclitaxel
Arm 2: Weekly paclitaxel plus TAK228ExperimentalPaclitaxel, concentrate for solution for infusion 80mg per metre squared on day 1, 8 and 15 of a 28 day cycle. Cycles continue until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria TAK228, oral capsule 4mg on days 2-4, 9-11, 16-18 and 23-25 of a 28 day cycle i.e. in concurrence with paclitaxel. Cycles continue until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria
Receives: Drug: Paclitaxel; Drug: TAK228

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 12 months

Secondary outcomes (10)

  1. 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

    Measured: 6 months

  2. Overall Response Rate (ORR)

    ORR (as assessed by RECIST v1.1) defined by complete response (CR) or partial response (PR)

    Measured: 12 months

  3. 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)

    Measured: 12 months

  4. Time to Progression (TTP)

    TTP defined as time from study entry to first evidence of disease progression or death due to any cause

    Measured: 12 months

  5. 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

    Measured: 4 months

  6. 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

    Measured: 12 months

  7. Overall Survival (OS)

    OS defined as time from study entry to death due to any cause or to study termination

    Measured: 12 months

  8. 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

    Measured: 12 months

  9. 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

    Measured: 12 months

  10. 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

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2018
  2. Study start21 Sep 2018
  3. Primary completion30 Nov 2023
  4. Study completion30 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03648489
Sponsor's protocol ID
C/30/2011
Acronym
DICE
Status last verified
Sep 2024
First submitted
22 Aug 2018
Last updated
20 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Fiorentino F, Krell J, de la Rosa CN, Webber L. DICE: 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. Trials. 2022 Apr 5;23(1):261. doi: 10.1186/s13063-022-06201-3.

    PubMed 35382842

  • de la Rosa CN, Krell J, Day E, Clarke A, Reddi M, Webber L, Fiorentino F. 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). Trials. 2022 Jan 5;23(1):13. doi: 10.1186/s13063-021-05669-9.

    PubMed 34986897

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Paclitaxel and TAK228 in people with Ovarian Cancer and Ovarian Neoplasms, run by Imperial College London at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03648489, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2024.

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