Trial Title:
DETERMINE Trial Treatment Arm 02: Atezolizumab in Adult, Teenage/Young Adults and Paediatric Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition
NCT ID:
NCT05770102
Condition:
Malignancy
Malignant Neoplasm
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms by Site
Cancer
Colorectal Neoplasms
Endometrial Neoplasms
Melanoma
Conditions: Official terms:
Neoplasms
Colorectal Neoplasms
Neoplasms by Site
Endometrial Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Atezolizumab
Conditions: Keywords:
Adult
Antineoplastic Agents
Atezolizumab
Cancer
Child
Malignancy
Malignant Neoplasms
Molecular Targeted Therapy
Neoplasms by Histologic Type
Neoplasms by Site
Paediatric
Precision Medicine
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:
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 02: Atezolizumab
Other name:
Tecentriq
Summary:
This clinical trial is looking at a drug called atezolizumab. Atezolizumab is approved as
standard of care treatment for adult patients with urothelial cancer, non-small cell lung
cancer, extensive-stage breast small cell lung cancer, hepatocellular carcinoma and
triple negative cancer. This means it has gone through clinical trials and been approved
by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.
Atezolizumab works in patients with these types of cancers which have certain changes in
the cancer cells called high tumour mutational burden (TMB) or high microsatellite
instability (MSI) or proven (previously diagnosed) constitutional mismatch repair
deficiency (CMMRD).
Investigators now wish to find out if it will be useful in treating patients with other
cancer types which are also TMB/MSH-high or show CMMRD. 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 02 (atezolizumab) aims to evaluate the efficacy of atezolizumab
in adult, paediatric and teenage/young adult (TYA) patients with rare* cancers with high
TMB or high MSI or proven CMMRD disposition and in common cancers where high TMB/MSI or
proven CMMRD 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.
Screening: Consenting participants undergo biopsy and collection of blood samples for
research purposes.
Treatment: Participants will receive atezolizumab 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 02 (ATEZOLIZUMAB) OUTLINED BELOW*
*When atezolizumab-specific inclusion/exclusion criteria or precautions below differ from
those specified in the Master Protocol, the atezolizumab-specific criteria will take
precedence.
Inclusion Criteria:
A. Confirmed diagnosis of a malignancy that is high TMB (defined as ≥10 mut/Mb), MSI-high
or of proven (previously diagnosed) CMMRD disposition using an analytically validated
method.
B. Women of childbearing potential are eligible provide they meet the following criteria:
- Have a negative serum or urine pregnancy test before enrolment and;
- Agree to use one form of 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 or without 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,
VIII. male or female condom with or without spermicide;
IX. cap, diaphragm or sponge with spermicide.
Effective from the first administration of atezolizumab, throughout the trial and for
five months after the last administration of atezolizumab.
C. Male patients with partners who are women of childbearing potential are eligible
provided that they agree to the following, from the first administration of atezolizumab,
throughout the trial and for five months after the last administration of atezolizumab:
- Agree to take measures not to father children by using a barrier method of
contraception 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 an effective method of
contraception as in B.
- Male patients with pregnant or lactating partners must be advised to use barrier
method contraception (e.g. condom) 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)
Lymphocyte count: ≥0.5×10^9/L
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
Bilirubin: <1.5 × upper limit of normal (ULN). Patients with known Gilbert disease: total
bilirubin ≤3 × ULN
Serum albumin: ≥25 g/L (2.5 g/dL)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5 × 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 × ULN (unless patient is on
anticoagulants, e.g. warfarin [INR should be stable and within indicated therapeutic
range] or direct oral anticoagulants [DOAC]).
Amylase: ≤1.5 × ULN
Estimated glomerular filtration rate (eGFR): ≥30 mL/mi
F. Patients must have stable thyroid function tests. Patients on stable doses of
thyroxine replacement are permitted
G. PAEDIATRIC PATIENTS (there is no lower age limit for 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 (Hb): ≥80 g/L (transfusion allowed)
Lymphocyte Count: ≥0.5×10^9/L
Absolute neutrophil count (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 × ULN for age with the following exception: Patients with known Gilbert
disease: total bilirubin ≤3 × ULN.
Serum albumin: ≥25 g/L (2.5 g/dL)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5 × ULN for age
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 × ULN (unless patient is on
anticoagulants, e.g. warfarin [INR should be stable and within indicated therapeutic
range], or DOAC).
Amylase: ≤1.5 × ULN.
Estimated glomerular filtration rate (eGFR): >60 mL/min (uncorrected value)
H. Patients must have stable thyroid function tests. Patients on stable doses of
thyroxine replacement are permitted
Exclusion Criteria:
A. Diagnosis of urothelial cancer, non-small cell lung cancer, extensive-stage small cell
lung cancer, hepatocellular carcinoma or triple negative breast cancer.
B. 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 IMP administration. 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 the start of IMP
administration. Primary brain or central nervous system (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.
•Paediatric patients with either primary brain tumours or extracranial solid tumours with
intracranial metastases with one or more intracranial lesions should only be considered
for inclusion if largest intracranial lesion is ≤6 cm in longest axis. Consideration
should also be given to the intracranial location of the tumour and potential risk should
swelling occur. This is because of the class risk of immune checkpoint inhibitors such as
atezolizumab causing immune-mediated inflammatory response and 'tumour flare' which may
result in acute neurological deterioration.
C. Female patients who are pregnant, breastfeeding or planning to become pregnant during
the trial or within five months following their last dose of atezolizumab.
D. History or clinical evidence of current inflammatory lung disease:
- History of idiopathic pulmonary fibrosis, organising pneumonia (e.g. bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
- Evidence of active pneumonitis on screening chest computed tomography (CT) scan.
E. Active autoimmune disease that requires the use of systemic immunomodulatory therapy
(i.e. with disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy for hypothyroidism and adrenal or pituitary insufficiency is
acceptable.
F. Ongoing lung pathologies which, in the opinion of the Investigator present a
compromise to safety (e.g. active tuberculosis).
G. Systemic immunomodulatory agents within 14 days prior to trial entry
(immunostimulatory agents within four weeks). Exceptions to this are:
- Patients who received acute, low dose systemic immunosuppressant medication or a
one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of
corticosteroids for a contrast allergy) are eligible for the trial.
- Patients who received corticosteroids for chronic obstructive pulmonary disease
(COPD) or asthma equivalent to ≤10 mg prednisolone a day or asthma, or low-dose
corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible
for the trial.
- Patients with primary CNS disease can be receiving concurrent treatment with
corticosteroids. Patients must be receiving a stable or decreasing dose for ≥14 days
for adults and ≥7 days for paediatric patients prior to the screening magnetic
resonance imaging (MRI) scan and at the time of drug initiation.
- Patients who receive physiological doses of steroid replacement (e.g.
hydrocortisone) are permitted.
H. Known to be serologically positive (as detected by polymerase chain reaction) for
hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
I. History of severe allergic anaphylactic reactions to chimeric, human or humanised
antibodies, or fusion proteins including other immune checkpoint inhibitors.
J. Known hypersensitivity to Chinese hamster ovary cell products.
K. Known hypersensitivity to atezolizumab or any of the excipients.
L. Patients who were administered a live, attenuated vaccine within 28 days prior to
enrolment, or anticipation of need for such a vaccine during atezolizumab treatment or
within five months after the final dose of atezolizumab.
M. Patients with clinically significant pre-existing cardiac conditions, including
uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or
NYHA class III or IV congestive heart failure.
Patients with a cerebrovascular event (including stroke or transient ischaemic attacks
[TIA]) or cardiovascular event (including acute myocardial infarction [MI]) within three
months before the first dose of atezolizumab.
N. Prior allogeneic stem cell or solid organ transplantation on immunosuppression.
O. Prior treatment with the same class of drug unless genetic profile demonstrates a
mechanism of resistance known to be potentially sensitive to atezolizumab.
P. Uncontrolled diabetes.
Q. Any clinically significant concomitant disease or condition (or its treatment) that
could interfere with the conduct of the trial or absorption of oral medications or 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:
Not yet 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:
Not yet 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:
Not yet 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:
October 25, 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/NCT05770102
http://CRUK.org/determine
https://clinicaltrials.gov/ct2/show/NCT05722886
