Trial Title:
DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol
NCT ID:
NCT05722886
Condition:
Solid Tumor
Haematological Malignancy
Conditions: Official terms:
Neoplasms
Hematologic Neoplasms
Trastuzumab
Atezolizumab
Pertuzumab
Vemurafenib
Alectinib
Entrectinib
Conditions: Keywords:
Adult
Alectinib
ALK Tyrosine Kinase Receptor
Antineoplastic Agents
Atezolizumab
BRAF Kinase
Cancer
Child
CMMRD
Cobimetinib
Entrectinib
Genes, HER2
Immune Checkpoint Inhibitors
Immunological
Lymphoproliferative Disorders
Malignancy
Malignant Neoplasms
MSI
Molecular Targeted Therapy
Mutation
Neoplasms by Histologic Type
Neoplasms by Site
Paediatric
Pertuzumab
Precision Medicine
Protein Kinase Inhibitors
Rare
ROS1 protein, human
TMB
Trastuzumab
Tumour-agnostic
Vemurafenib
Young adult
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Alectinib
Description:
Adult participants will be administered alectinib orally at a dose of 600 mg (four 150 mg
capsules) twice daily.
Paediatric participants with a body weight ≥40 kg and who are able to swallow the
capsules will be administered alectinib orally at a dose of 600 mg (four 150 mg capsules)
twice daily.
Each cycle of treatment will consist of 28 days and participants may continue on
treatment until disease progression, unacceptable toxicity or withdrawal of consent.
Arm group label:
Treatment Arm 1: Alectinib
Other name:
Alecensa
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Adult participants will receive 1200 mg of atezolizumab intravenously every 21 days.
Paediatric participants will receive atezolizumab at a dose of 15 mg/kg (maximum 1200 mg)
every 21 days.
Participants may continue on treatment until disease progression, unacceptable toxicity
or withdrawal of consent.
Arm group label:
Treatment Arm 2: Atezolizumab
Other name:
Tecentriq
Intervention type:
Drug
Intervention name:
Entrectinib
Description:
Adult and paediatric participants with body surface area (BSA) ≥1.51 m^2 will receive
entrectinib orally at a dose of 600 mg daily dose (three 200 mg capsules per day).
Paediatric participants will receive a dose adjusted for BSA. Each cycle of treatment
will consist of 28 days and participants may continue until disease progression,
unacceptable toxicity or withdrawal of consent.
Arm group label:
Treatment Arm 3: Entrectinib
Other name:
Rozlytrek
Intervention type:
Drug
Intervention name:
Trastuzumab in combination with pertuzumab
Description:
The initial loading dose of trastuzumab is 8 mg/kg body weight administered intravenously
every 21 days followed thereafter by a maintenance dose of 6 mg/kg body weight.
The initial loading dose of pertuzumab is 840 mg administered intravenously every 21 days
followed thereafter by a maintenance dose of 420 mg.
Participants may continue until disease progression, unacceptable toxicity or withdrawal
of consent.
Arm group label:
Treatment Arm 4: Trastuzumab in combination with pertuzumab
Other name:
Herceptin in combination with Perjeta
Intervention type:
Drug
Intervention name:
Vemurafenib in combination with cobimetinib
Description:
Participants will receive vemurafenib at a dose of 960 mg (4 tablets of 240 mg) orally on
a twice daily schedule throughout a 28-day cycle.
Participants will receive cobimetinib at a dose of 60 mg (3 tablets of 20 mg) to be taken
orally, once daily for 21 consecutive days (days 1 to 21 in each 28-day cycle); followed
by a 7-day break.
Participants may continue on treatment until disease progression, unacceptable toxicity
or withdrawal of consent.
Arm group label:
Treatment Arm 5: Vemurafenib in combination with cobimetinib
Other name:
Zelboraf in combination with Cotellic
Summary:
DETERMINE is an open-label phase II/III trial. It will look at targeted treatments in
rare cancers or common cancers with rare genetic change (mutation). Participants must
have a cancer with an identified mutation. This could be found during routine testing or
as part of another research programme. The DETERMINE trial will recruit adults, teenagers
and children. If a drug is found to benefit a new patient group, the study team will work
with the NHS and the Cancer Drugs Funds to see if these drugs can be available for
patients in the future. This clinicaltrials.gov record refers to the Overall Trial
Protocol (Master Screening Record), additional records will be added to
clinicaltrials.gov for each treatment arm.
Detailed description:
DETERMINE is an umbrella-basket platform trial to evaluate the efficacy of licensed
targeted therapies in rare* adult, paediatric and teenage/young adult (TYA) cancers with
actionable genomic alterations, including common cancers with rare actionable
alterations.
*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes
paediatric and teenagers/young adult cancers) or common cancers with rare alterations.
The number of treatment arms opened will depend on the number of licensed medicines
identified for inclusion. Each trial cohort has a target sample size of 30 evaluable
patients. Sub-cohorts may be defined and further expanded where promising activity is
identified to a target of 30 evaluable patients each. The total number of patients
recruited to the platform will depend on the number of treatment arms and sub-cohorts
opened.
This clinicaltrials.gov record refers to the Overall Trial Protocol (Master Screening
Record), please refer to the references section for links to the individual treatment arm
records.
The main aims of the clinical trial arms are:
- To evaluate the anti-cancer activity of licensed targeted drugs outside their
license indication.
- To assess the safety and adverse event (AE) profile of licensed, targeted
anti-cancer drugs in the target population.
- To understand biological mechanisms for response and resistance to targeted
therapies.
- This Master Screening Record will capture the number of patients with a cancer
containing the appropriate genetic alteration that have been successfully allocated
and consented to each arm. The trial results (according to the protocol defined
outcome measures) will be reported per-arm for each treatment arm.
The ultimate aim is to translate positive clinical findings to NHS England to provide new
treatment options for rare adult, paediatric and TYA cancers.
Criteria for eligibility:
Criteria:
THE PARTICIPANT MUST FULFIL THE ELIGIBILITY CRITERIA OUTLINED BELOW AND WITHIN THE
SPECIFIC TREATMENT ARM APPENDIX TO WHICH THEY ARE ENROLLED.
Core Inclusion Criteria
1. Any patient with histologically proven locally advanced or metastatic cancer (solid
tumour or haematological malignancy) who has:
1. exhausted (or declined) standard-of-care treatment options.
2. or for whom no effective standard treatment is available*. *In exceptional
circumstances where upfront treatment on the CRUKD/21/004 DETERMINE trial is
considered the best choice for the patient in the opinion of the Investigator,
due to risk of considerable harm from standard treatment (e.g. where this
involves mutilating surgery or is unacceptable due to patient age or genetic
vulnerability such as CMMRD).
3. and whose disease has progressed, or is refractory.
2. Diagnosis of a rare cancer harbouring an actionable genomic alteration, or common
cancer types with rare actionable genomic alterations, that have been identified
using a validated sequencing technique and for which there is a relevant open
treatment arm within the DETERMINE trial.
3. Life expectancy of at least three months.
4. Patients are able to provide written (signed and dated) informed consent and be
capable of co-operating with treatment and follow-up. For patients under 16 years of
age, the parent or legal guardian will be asked to provide written informed consent
and the patient will be asked to provide age-appropriate assent (written or verbal,
commensurate with age and level of understanding).
5. Patients with objectively evaluable or measurable disease, according to an
assessment method appropriate for their cancer type.
6. Patients must provide a fresh tissue biopsy at baseline and blood samples for
translational research.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (ECOG performance
status 2 may be considered on an individual basis) (≥ 16 years), Karnofsky score ≥
50% (12 years to 15 years) or Lansky Play scales ≥ 50% (<12 years). Please see
specific treatment arm appendices for any variations on this criterion. Note:
Patients <16 years: patients with Central Nervous System (CNS) tumours and a
neurological deficit may be eligible with a performance status below 50%, at the
discretion of the Investigator. In such cases, the deficit must be stable for at
least 7 days prior to trial enrolment, be due to tumour or due to a post-surgical
adverse event that is deemed by the local Investigator.
8. Women of childbearing potential are eligible provided that they meet the following
criteria:
- Have a negative serum or urine pregnancy test before enrolment and
- Agree to the birth control methods and duration of use of those methods, as
specified in each treatment arm appendix.
9. Male patients with partners of childbearing potential are eligible provided that
they agree to the birth control methods and duration of use of those methods, as
specified in each treatment arm appendix.
Core exclusion criteria:
1. Ongoing AEs >Common Terminology Criteria of Adverse Events (CTCAE) Grade 2
attributable to previous anti-cancer treatments. Exceptions to this are any ongoing
toxic manifestation, which in the opinion of the Investigator should not exclude the
patient.
2. At high medical risk, in the opinion of the Investigator, because of non-malignant
systemic disease (including active uncontrolled infection).
3. Female patients who are pregnant, breastfeeding or planning to become pregnant or
male patients with a partner who is a woman of childbearing potential and is
planning to become pregnant during the trial or following the last dose of IMP, as
specified in each treatment arm appendix.
4. Is (or plans to be) a participant in another interventional clinical trial, whilst
taking part in this trial. Participation in an observational trial which does not
involve administration of an Investigational Medicinal Product (IMP) and which, in
the opinion of the local Investigator, would not place an unacceptable burden on the
patient would be acceptable e.g. sample collection* or Quality of Life (QoL)
studies.
*for paediatric patients participating in other studies involving tissue/circulating
tumour (ct) DNA/other blood collection, consideration would need to be given to the
total blood volumes collected (as per the European Medicines Agency blood volume
limits for children).
5. Co-administration of anti-cancer therapies other than those administered in this
trial.
6. Radiotherapy (except for palliative reasons) or chemotherapy, endocrine therapy,
nitrosoureas, mitomycin-C, immunotherapy and molecularly targeted agents or other
investigational medicinal products within 4 weeks or 5 half-lives (whichever is the
shorter).
7. Rapidly progressing or symptomatically deteriorating brain metastases. Patients with
previously treated brain metastases are eligible, provided the patient has not
experienced a seizure or had a clinically significant change in neurological status
within the two weeks prior to registration. Such patients must be non-dependent on
steroids or on a stable or reducing dose of steroid treatment for at least 14 days
(or 7 days for paediatric patients) prior to trial enrolment. Primary brain or CNS
malignancies are allowed providing the patient is clinically stable (if requiring
corticosteroids must be at stable or decreasing doses for at least 14 days for
adults and 7 days for paediatric patients prior to the start of IMP administration).
Patients who have received brain irradiation must have completed whole-brain
radiotherapy and/or stereotactic radiosurgery at least 14 days prior to the start of
IMP administration.
8. Any other condition which, in the opinion of the local Investigator, would not be in
the best interests of the patient.
Gender:
All
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Belfast City Hospital
Address:
City:
Belfast
Zip:
BT9 7AB
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Vicky Coyle, Prof
Email:
V.Coyle@qub.ac.uk
Investigator:
Last name:
Vicky Coyle, Prof
Email:
Principal Investigator
Facility:
Name:
University Hospital Birmingham
Address:
City:
Birmingham
Zip:
B15 2TT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Gary Middleton, Prof
Phone:
0121 371 3573
Email:
G.Middleton@bham.ac.uk
Investigator:
Last name:
Gary Middleton, Prof
Email:
Principal Investigator
Facility:
Name:
Birmingham Children's Hospital
Address:
City:
Birmingham
Zip:
B4 6NH
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Susanne Gatz, Dr
Phone:
0121 333 9999
Phone ext:
6266
Email:
Susanne.Gatz@nhs.net
Investigator:
Last name:
Susanne Gatz, Dr
Email:
Principal Investigator
Facility:
Name:
Bristol Royal Hospital for Children
Address:
City:
Bristol
Zip:
BS2 8BJ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Antony Ng, Dr
Phone:
0117 342 8044
Email:
Antony.Ng@uhbw.nhs.uk
Investigator:
Last name:
Antony Ng, Dr
Email:
Principal Investigator
Facility:
Name:
Bristol Haematology and Oncology Centre
Address:
City:
Bristol
Zip:
BS2 8ED
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Antony Ng, Dr
Phone:
0117 342 8044
Email:
Antony.Ng@uhbw.nhs.uk
Investigator:
Last name:
Antony Ng, Dr
Email:
Principal Investigator
Facility:
Name:
Addenbrooke's Hospital
Address:
City:
Cambridge
Zip:
CB2 OQQ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Bristi Basu, Dr
Phone:
01223 596105
Email:
bb313@medschl.cam.ac.uk
Investigator:
Last name:
Bristi Basu, Dr
Email:
Principal Investigator
Facility:
Name:
Velindre Cancer Centre
Address:
City:
Cardiff
Zip:
CF14 2TL
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Robert Jones, Dr
Phone:
02920 615888
Phone ext:
6327
Email:
Robert.Hugh.Jones@wales.nhs.uk
Investigator:
Last name:
Robert Jones, Dr
Email:
Principal Investigator
Facility:
Name:
Western General Hospital
Address:
City:
Edinburgh
Zip:
EH4 2XU
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Stefan Symeonides, Dr
Investigator:
Last name:
Stefan Symeonides, Dr
Email:
Principal Investigator
Facility:
Name:
The Beatson Hospital
Address:
City:
Glasgow
Zip:
G12 OYN
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Patricia Roxburgh, Dr
Phone:
0141 301 7118
Email:
Patricia.Roxburgh@glasgow.ac.uk
Investigator:
Last name:
Patricia Roxburgh, Dr
Email:
Principal Investigator
Facility:
Name:
Royal Hospital for Children Glasgow
Address:
City:
Glasgow
Zip:
G51 4TF
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Milind Ronghe, Dr
Phone:
0141 452 6692
Email:
Milind.Ronghe@ggc.scot.nhs.uk
Investigator:
Last name:
Milind Ronghe, Dr
Email:
Principal Investigator
Facility:
Name:
Leicester Royal Infirmary
Address:
City:
Leicester
Zip:
LE1 5WW
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Anne Thomas, Dr
Phone:
0116 2587601
Email:
at107@le.ac.uk
Investigator:
Last name:
Anne Thomas, Dr
Email:
Principal Investigator
Facility:
Name:
Alder Hey Hospital
Address:
City:
Liverpool
Zip:
L14 5AB
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Lisa Howell, Dr
Phone:
0151 293 3679
Email:
Lisa.Howell@alderhey.nhs.uk
Investigator:
Last name:
Lisa Howell, Dr
Email:
Principal Investigator
Facility:
Name:
The Royal Marsden Hospital
Address:
City:
London Borough of Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Lynley Marshall, Dr
Phone:
0208 661 3678
Email:
LynleyVanessa.Marshall@icr.ac.uk
Investigator:
Last name:
Lynley Marshall, Dr
Email:
Principal Investigator
Facility:
Name:
University College London Hospital
Address:
City:
London
Zip:
NW1 2BU
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Martin Foster, Prof
Phone:
020 3447 5085
Email:
M.Forster@ucl.ac.uk
Investigator:
Last name:
Martin Foster, Prof
Email:
Principal Investigator
Facility:
Name:
Guy's Hospital
Address:
City:
London
Zip:
SE1 9RT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
James Spicer
Phone:
020 7188 4260
Email:
james.spicer@kcl.ac.uk
Investigator:
Last name:
James Spicer, Dr
Email:
Principal Investigator
Facility:
Name:
Great Ormond Street Hospital
Address:
City:
London
Zip:
WC1N 3JH
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Darren Hargrave, Dr
Phone:
0207 813 8525
Email:
Darren.hargrave@gosh.nhs.uk
Investigator:
Last name:
Darren Hargrave, Dr
Email:
Principal Investigator
Facility:
Name:
Royal Manchester Children's Hospital
Address:
City:
Manchester
Zip:
M13 9WL
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Guy Makin, Dr
Phone:
0161 701 8419
Email:
Guy.Makin@mft.nhs.uk
Investigator:
Last name:
Guy Makin, Dr
Email:
Principal Investigator
Facility:
Name:
The Christie Hospital
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Matthew Krebs, Prof
Phone:
0161 918 7672
Email:
Matthew.Krebs@nhs.net
Investigator:
Last name:
Matthew Krebs
Email:
Principal Investigator
Facility:
Name:
Great North Children's Hospital
Address:
City:
Newcastle
Zip:
NE1 4LP
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Alastair Greystoke, Dr
Phone:
0191 2138476
Email:
Alastair.Greystoke@newcastle.ac.uk
Investigator:
Last name:
Alastair Greystoke, Dr
Email:
Principal Investigator
Facility:
Name:
Freeman Hospital
Address:
City:
Newcastle
Zip:
NE7 7DN
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Alastair Greystoke, Dr
Phone:
0191 2138476
Email:
Greystoke@newcastle.ac.uk
Investigator:
Last name:
Alastair Greystoke, Dr
Email:
Principal Investigator
Facility:
Name:
Churchill Hospital
Address:
City:
Oxford
Zip:
OX3 7LE
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Sarah Pratap, Dr
Phone:
01865 235273
Email:
Sarah.Pratap@ouh.nhs.uk
Investigator:
Last name:
Sarah Pratap, Dr
Email:
Principal Investigator
Facility:
Name:
John Radcliffe Hospital
Address:
City:
Oxford
Zip:
OX3 9DU
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Sarah Pratap, Dr
Phone:
01865 235273
Email:
Sarah.Pratap@ouh.nhs.uk
Investigator:
Last name:
Sarah Pratap, Dr
Email:
Principal Investigator
Facility:
Name:
Weston Park Hospital
Address:
City:
Sheffield
Zip:
S10 2SJ
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Sarah Danson, Dr
Phone:
0114 226 5068
Email:
s.danson@sheffield.ac.uk
Investigator:
Last name:
Sarah Danson, Dr
Email:
Principal Investigator
Facility:
Name:
Southampton General Hospital
Address:
City:
Southampton
Zip:
SO16 6YD
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Juliet Gray, Prof
Phone:
0238 120 6639
Email:
Juliet.Gray@uhs.nhs.uk
Investigator:
Last name:
Juliet Gray, Prof
Email:
Principal Investigator
Facility:
Name:
Clatterbridge Cancer Centre
Address:
City:
Wirral
Zip:
CH63 4JY
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Dan Palmer, Dr
Phone:
0151 706 4172 / 0151 706 4177
Email:
daniel.palmer@liverpool.ac.uk
Investigator:
Last name:
Dan Palmer, Dr
Email:
Principal Investigator
Start date:
March 1, 2023
Completion date:
October 2029
Lead sponsor:
Agency:
Cancer Research UK
Agency class:
Other
Collaborator:
Agency:
University of Manchester
Agency class:
Other
Collaborator:
Agency:
University of Birmingham
Agency class:
Other
Collaborator:
Agency:
Royal Marsden NHS Foundation Trust
Agency class:
Other
Collaborator:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
Cancer Research UK
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05722886
http://CRUK.org/determine
https://clinicaltrials.gov/ct2/show/NCT05770037
https://clinicaltrials.gov/ct2/show/NCT05770102
https://clinicaltrials.gov/ct2/show/NCT05770544
https://clinicaltrials.gov/ct2/show/NCT05786716
https://clinicaltrials.gov/ct2/show/NCT05768178
