Trial Title:
DETERMINE Trial Treatment Arm 01: Alectinib in Adult, Teenage/Young Adults (TYA) and Paediatric Patients With ALK Positive Cancers
NCT ID:
NCT05770037
Condition:
Solid Tumor
Haematological Malignancy
Malignant Neoplasm
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms by Site
Cancer
Anaplastic Large Cell Lymphoma
Lymphoma
Renal Cell Carcinoma
Neuroblastoma
Conditions: Official terms:
Lymphoma
Neoplasms
Neuroblastoma
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Site
Hematologic Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Alectinib
Conditions: Keywords:
Adult
Alectinib
ALK Tyrosine Kinase Receptor
Antineoplastic Agents
Cancer
Child
Malignancy
Malignant Neoplasms
Molecular Targeted Therapy
Mutation
Neoplasms by Histologic Site
Neoplasms by Site
Paediatric
Precision Medicine
Protein Kinase Inhibitors
Rare
Tumour-agnostic
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 01: Alectinib
Other name:
Alecensa
Summary:
This clinical trial is looking at a drug called alectinib. Alectinib is approved as
standard of care treatment for adult patients with certain types of lung cancer. This
means it has gone through clinical trials and been approved by the Medicines and
Healthcare products Regulatory Agency (MHRA) in the UK. Alectinib works in lung cancer
patients with a particular mutation in their cancer known as ALK.
Investigators now wish to find out if it will be useful in treating patients with other
cancer types which have the same mutation. If the results are positive, the study team
will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely
accessed for patients in the future.
This trial is part of a trial programme called DETERMINE. The programme will also look at
other anti-cancer drugs in the same way, through matching the drug to rare cancer types
or ones with specific mutations.
Detailed description:
DETERMINE Treatment Arm 01 (alectinib) aims to evaluate the efficacy of alectinib in
ALK-positive rare* adult, paediatric and teenage/young adult (TYA) cancers and in common
cancers where an ALK mutation or amplification is considered to be infrequent.
*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.
This treatment arm 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 ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs
Fund) to provide new treatment options for rare adult, paediatric and TYA cancers.
OUTLINE:
Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the
participant based on molecularly-defined cohorts (See information on Master Screening
Protocol below).
Screening: Consenting participants undergo biopsy and collection of blood samples for
research purposes.
Treatment: Participants will receive alectinib until disease progression, unacceptable
toxicity or withdrawal of consent. Participants will also undergo collection of blood
samples at various intervals while receiving treatment and at EoT.
After completion of study treatment, patients are followed up every 3 months for 2 years.
THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL:
Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for
information on the DETERMINE Trial Master Protocol and applicable documents.
Criteria for eligibility:
Criteria:
THE PARTICIPANT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL
(NCT05722886) AND WITHIN THE TREATMENT ARM 01 (ALECTINIB) OUTLINED BELOW*
*When alectinib-specific inclusion/exclusion criteria or precautions below differ from
those specified in the Master Protocol, the Alectinib-specific criteria will take
precedence.
Inclusion Criteria:
A. Confirmed diagnosis of an ALK-positive malignancy using an analytically validated
method.
B. 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 use one form of highly effective birth control method such as:
I. combined (oestrogen and progestogen containing) hormonal contraception associated with
inhibition of ovulation [oral, intravaginal or transdermal])
II. progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable or implantable)
III. intrauterine device (IUD)
IV. intrauterine hormone-releasing system (IUS)
V. bilateral tubal occlusion
VI. vasectomised partner
VII. sexual abstinence
Effective from the first administration of alectinib, throughout the trial and for three
months after the last administration of alectinib.
C. Male patients with partners who are women of childbearing potential are eligible
provided that they agree to the following, from first administration of alectinib,
throughout the trial and for three months after the last administration of alectinib:
- Agree to take measures not to father children by using a barrier method of
contraception (condom plus spermicide) or sexual abstinence.
- Non-vasectomised male patients with partners who are women of childbearing potential
must also be willing to ensure that their partner uses a highly effective method of
contraception, as in criterion B, above.
- Male patients with pregnant or lactating partners must be advised to use barrier
method contraception (for example, condom plus spermicide) to prevent drug exposure
of the foetus or neonate.
D. Patients must be able and willing to undergo a fresh biopsy.
E. ADULT PATIENTS: Adequate organ function as per haematological and biochemical indices
within the ranges shown below. These measurements should be performed to confirm the
patient's eligibility.
Haemoglobin (Hb): ≥90 g/L (transfusion allowed)
Absolute neutrophil count (ANC): ≥1.5×10^9/L (no granulocyte colony-stimulating factor
[GCSF] support in preceding 72 hours)
Platelet count:≥100×10^9/L (unsupported for 72 hours)
Bilirubin: <1.5 x upper limit of normal (ULN) or ≤2.5 x ULN if raised due to metastases
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5 x ULN or ≤ 5
ULN if raised due to metastases
Coagulation - prothrombin (PT) (or international normalized ratio [INR]) and activated
partial thromboplastin clotting time (aPTT) : ≤1.5 x lower limit of normal (LLN)/ULN
(unless patient is on anticoagulants e.g. warfarin [INR should be stable and within
indicated therapeutic range], or direct oral anticoagulants [DOAC])
Estimated glomerular filtration rate (eGFR): eGFR: ≥30 mL/min (uncorrected value)
F. PAEDIATRIC PATIENTS: Adequate organ function as per haematological and biochemical
indices within the ranges shown below. These measurements should be performed to confirm
the patient's eligibility
Haemoglobin: ≥80 g/L (transfusion allowed)
ANC: ≥1.0×10^9/L (no GCSF support in preceding 72 hours)
Platelet count: ≥75×10^9/L (unsupported for 72 hrs)
Bilirubin: ≤1.5 x ULN for age or <2.5 x ULN if raised due to metastases
ALT and AST: ≤3.0 x ULN or ≤ 5 ULN if raised due to metastases
Coagulation - PT or INR and aPTT: For patients not receiving therapeutic anticoagulation:
INR and aPTT ≤1.5 x ULN for age. For patients receiving therapeutic anticoagulation:
stable anticoagulant regimen, e.g. warfarin (INR should be stable and within indicated
therapeutic range) or DOAC.
eGFR: eGFR: ≥60 mL/min/1.73m^2
Exclusion Criteria:
A. Diagnosis of ALK-positive non-small cell lung cancer.
B. Female patients who are pregnant, breastfeeding or planning to become pregnant during
the trial or for three months following their last dose of alectinib.
C. Patients with 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 14 days prior to the start of alectinib administration. Such patients must be
nondependent on steroids or on a stable or reducing dose of steroid treatment for at
least 14 days (or one week for paediatric patients) prior to the start of alectinib
administration. 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
alectinib 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 alectinib administration.
D. Prior treatment with the same class of drug unless genetic profile demonstrates a
mechanism of resistance known to be potentially sensitive to alectinib.
E. History of or radiological evidence of interstitial lung disease and/or pneumonitis.
Prior localised radiotherapy related pneumonitis is permitted if resolved and off
steroids and asymptomatic for >6 months.
F. Patients at risk of gastrointestinal (GI) perforation e.g. history of diverticulitis,
concomitant use of medicinal product with a recognized risk of gastrointestinal
perforation (unless patient has also been co-prescribed gastric protection). Patients who
present with a GI primary tumour or metastases to the GI tract may be considered.
G. Patient unable to swallow or tolerate oral medication or any GI disorder that may
affect absorption of oral medications, such as malabsorption syndrome or following major
bowel resection. Paediatric patients will be excluded if they are unable to swallow the
capsules, as per the dosing schedule (150 mg dose strength).
H. Patients with clinically significant pre-existing cardiac conditions, including
uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias
(within three months), or New York Heart Association (NYHA) class III or IV congestive
heart failure. Patients with a cerebrovascular event (including stroke or transient
ischaemic attack [TIA]), or cardiovascular event (including acute myocardial infarction
[MI]), within three months before the first dose of alectinib.
I. History of organ transplantation.
J. Symptomatic bradycardia for age.
K. Known hypersensitivity to alectinib or any of the excipients.
L. Active hepatitis B or C virus or known human immunodeficiency virus (HIV) positivity
or acquired immune deficiency syndrome related illness.
M. Familial or personal history of congenital bone disorders, bone metabolism alterations
or known osteopenia in the patient.
N. Any clinically significant concomitant disease or condition (or it's treatment) that
could interfere with, the conduct of the trial or absorption of oral medications that
would, in the opinion of the Investigator, pose an unacceptable risk to the patient in
this trial.
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
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Susanne Gatz, Dr
Phone:
0121 333 9999
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:
Not yet 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:
Not yet 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:
Not yet 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:
Not yet 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:
Leeds General Infirmary
Address:
City:
Leeds
Zip:
LS1 3EX
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Martin Elliott, Dr
Phone:
0113 392 8779
Email:
martin.elliott1@nhs.net
Investigator:
Last name:
Martin Elliott, 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:
Not yet 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:
Not yet 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, Dr
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, Prof
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:
December 18, 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/NCT05770037
http://CRUK.org/determine
https://clinicaltrials.gov/ct2/show/NCT05722886
