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) (DICE)

  • STATUS
    Recruiting
  • days left to enroll
    76
  • participants needed
    126
  • sponsor
    Imperial College London
Updated on 16 February 2022
paclitaxel
cancer
serum pregnancy test
measurable disease
dexamethasone
metastasis
carboplatin
cancer chemotherapy
ovarian cancer
fallopian tube
carcinosarcoma
peritoneal cancer
primary peritoneal carcinoma
recurrent ovarian cancer

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 cancer has returned/grown significantly during or within 6 months of platinum-containing chemotherapy).

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.

Details
Condition Ovarian Cancer, Ovarian Neoplasms, Ovarian Carcinosarcoma, Ovarian Serous Adenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Clear Cell Adenocarcinoma, Fallopian Tube Cancer, Fallopian Tube Neoplasms, Primary Peritoneal Carcinoma, Primary Peritoneal Serous Adenocarcinoma
Treatment Paclitaxel, TAK228
Clinical Study IdentifierNCT03648489
SponsorImperial College London
Last Modified on16 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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 (5m 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

Exclusion Criteria

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
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note