Trial Title:
DETERMINE Trial Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.
NCT ID:
NCT05768178
Condition:
Solid Tumor
Haematological Malignancy
Melanoma
Thyroid Cancer, Papillary
Ovarian Neoplasms
Colorectal Neoplasms
Laryngeal Neoplasms
Carcinoma, Non-Small-Cell Lung
Glioma
Multiple Myeloma
Erdheim-Chester Disease
Thyroid Carcinoma, Anaplastic
Conditions: Official terms:
Carcinoma
Neoplasms
Multiple Myeloma
Thyroid Neoplasms
Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Ovarian Neoplasms
Hematologic Neoplasms
Laryngeal Neoplasms
Thyroid Cancer, Papillary
Thyroid Carcinoma, Anaplastic
Erdheim-Chester Disease
Thyroid Diseases
Vemurafenib
Conditions: Keywords:
Adult
Antineoplastic Agents
Cancer
Malignancy
Malignant Neoplasms
Molecular Targeted Therapy
Mutation
Neoplasms by Histologic Type
Neoplasms by Site
Precision Medicine
Cobimetinib
Proto-Oncogene Proteins B-raf
Rare
Tumour-agnostic
Vemurafenib
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:
Vemurafenib
Description:
Participants will receive vemurafenib at a dose of 960 mg orally on a twice daily
schedule throughout a 28-day cycle.
Arm group label:
Treatment Arm 05- Vemurafenib and Cobimetinib
Other name:
Zelboraf
Intervention type:
Drug
Intervention name:
Cobimetinib
Description:
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.
Arm group label:
Treatment Arm 05- Vemurafenib and Cobimetinib
Other name:
Cotellic
Summary:
This clinical trial is looking at a combination of drugs called vemurafenib and
cobimetinib. Vemurafenib is approved as standard of care for adult patients with
unresectable or metastatic melanoma. Cobimetinib is approved as standard of care in
combination with vemurafenib for the treatment of adult patients with unresectable or
metastatic melanoma.
Cobimetinib and vemurafenib work in patients with these types of cancers which have
certain changes in the cancer cells called BRAF V600 mutation-positive.
Investigators now wish to find out if it will be useful in treating patients with other
cancer types which are also BRAF V600 mutation-positive. 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 05 (vemurafenib and Cobimetinib) aims to evaluate the efficacy of
vemurafenib and cobimetinib in adult patients with rare* cancers with BRAF V600 mutations
or in common cancers where BRAFV600 mutations and considered to be infrequent.
*Rare is defined generally as incidence less than 6 cases in 100,000 patients 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 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 vemurafenib and cobimetinib 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:
Inclusion Criteria:
A. Confirmed diagnosis of a malignancy harbouring any actionable BRAF V600 mutation using
an analytically validated sequencing technique (result does not need to be confirmed at
screening unless not tested within 18 months, in which case, repeat analysis is
required).
B. Adult patients ≥16 years old.
C. Patients must be able and willing to undergo a fresh biopsy.
D. 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)
Patients with known Gilbert disease: total bilirubin ≤3.0 x ULN
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5 x ULN or ≤ 5
ULN if raised due to presence of liver metastases
estimated glomerular filtration rate (eGFR): ≥30 mL/min (uncorrected value)
Coagulation- Prothrombin (PT) (or international normalized ratio (INR), and activated
partial thromboplastin clotting time (aPTT): INR or PT ≤1.5 and aPTT <1.5x ULN (unless
patient is on anticoagulants e.g. warfarin [INR should be stable and within therapeutic
range], or direct oral anticoagulants [DOAC]
Electrolytes- Potassium (K), Magnesium (Mg) and Calcium (Ca): Electrolytes within normal
range (electrolyte replacement permitted)
E. 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 any two forms of highly effective or effective methods together (at
least one to be non-hormonal) such as:
- Highly effective methods:
- combined (oestrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation (oral, intravaginal, transdermal)
- progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, implantable)
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomised partner
- sexual abstinence
- Effective methods:
- progestogen-only oral hormonal contraception not associated with inhibition of
ovulation
- male or female condom with or without spermicide
- cap, diaphragm or sponge with spermicide
Effective from the first administration of vemurafenib or cobimetinib (whichever is
first), throughout the trial and for six months after the last administration of
vemurafenib or cobimetinib (whichever is later).
F. Male patients with partners who are women of childbearing potential, are eligible
provided that they agree to the following, from the first administration of vemurafenib
or cobimetinib (whichever is first), throughout the trial and for six months after the
last administration of vemurafenib or cobimetinib (whichever is later):
- Agree to take measures not to father children by using a barrier method of
contraception (condom plus spermicide) or to 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 E, 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.
Exclusion Criteria:
A. Diagnosis of unresectable or metastatic melanoma with a BRAF V600 mutation.
B. Female patients who are pregnant, breastfeeding or planning to become pregnant during
the trial or for six months following their last dose of vemurafenib or cobimetinib,
whichever is later.
C. Patients with QTcF (Corrected QT interval by Fridericia) at screening of >450ms for
males and >470ms for females measured on triplicate ECG (if 1/3 readings show >450/470ms
then patient is ineligible).
D. Patients with any history of long QT syndrome or Torsades de Pointes (or any
concurrent medication with a known risk of inducing Torsades de Pointes).
E. Known hypersensitivity to vemurafenib or cobimetinib or any of the excipients.
F. Patients with clinically significant pre-existing cardiac conditions including (within
the last three months prior to screening):
- Uncontrolled or symptomatic angina,
- Uncontrolled atrial or ventricular arrhythmias,
- Class III & IV New York Heart Association (NYHA) congestive heart failure,
- Left ventricular ejection fraction (LVEF) <50%,
- Myocardial infarction
G. Ophthalmological disorders: History of retinal detachment, severe visual impairment,
central serous chorioretinopathy, neovascular retinopathy, or retinopathy of prematurity.
Patients with low grade gliomas causing visual impairment may be considered eligible and
monitored with close ophthalmological monitoring.
H. History of pancreatitis.
I. History of central nervous system (CNS) or gastrointestinal (GI) haemorrhage within
three months of trial entry.
J. Patients with any history of haemorrhagic stroke.
K. Prior treatment with the same class of drug unless presence of a resistance alteration
known to be potentially sensitive to either vemurafenib or cobimetinib. Prior sorafenib
use is permissible following a washout period of 10 days.
L. 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 prior to the start of IMP 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 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.
M. 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:
18 Years
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:
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:
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:
University College London Hospital
Address:
City:
London
Zip:
NW1 2BU
Country:
United Kingdom
Status:
Not yet 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:
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:
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:
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/NCT05768178
http://CRUK.org/determine
https://clinicaltrials.gov/ct2/show/NCT05722886
