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)

NCT03648489 | Completed Phase 2 DMC

• 1 other identifier: C/30/2011
• Study Type: interventional
• Target: 134
• Locations: 2 countries
• Sites: 15

Brief 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).

Conditions

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

Keywords

TAK228; TAK-228; Paclitaxel; Ovarian cancer; Platinum resistant

Outcome Measures

Primary Outcomes (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

  12 months

Secondary Outcomes (10)

• Progression Free Survival (PFS) at 24 weeks

  6 months

• Overall Response Rate (ORR)

  12 months

• Duration of Response (DOR)

  12 months

• Time to Progression (TTP)

  12 months

• Clinical Benefit Rate (CBR) at 4 months

  4 months

Study Arms (2)

Arm 1: Weekly paclitaxel alone

ACTIVE COMPARATOR

Paclitaxel, 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

Drug: Paclitaxel

Arm 2: Weekly paclitaxel plus TAK228

EXPERIMENTAL

Paclitaxel, 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

Drug: Paclitaxel; Drug: TAK228

Interventions

Paclitaxel DRUG

Please refer to arm/group description

Arm 1: Weekly paclitaxel alone; Arm 2: Weekly paclitaxel plus TAK228

TAK228 DRUG

Please refer to arm/group description

Arm 2: Weekly paclitaxel plus TAK228

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (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

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead
• Takeda Pharmaceuticals International, Inc.: collaborator
• North Eastern German Society of Gynaecological Oncology: collaborator

Study Sites (15)

Charité Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Germany

Location

KEM Kliniken Essen-Mitte

Essen, Germany

Location

Furness General Hospital

Barrow in Furness, Cumbria, LA14 4LF, United Kingdom

Location

St George's University Hospitals NHS Foundation Trust

London, Greater London, SW17 0QT, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, Greater London, SW3 6JJ, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, Greater London, W12 0HS, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, Greater London, SM2 5PT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Royal Lancaster Infirmary

Lancaster, Lancashire, LA1 4RP, United Kingdom

Location

Mount Vernon Cancer Centre

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 35382842 DERIVED

• 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.

  PMID: 34986897 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Paclitaxel; sapanisertib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jonathan Krell

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 27, 2018
• Study Start: September 21, 2018
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: September 20, 2024

Record last verified: 2024-09

Locations

DE (3); GB (12)