Primary Objectives:To determine the efficacy of brigatinib, as evidenced by confirmed objective response rate (ORR), in patients with ALK+ locally advanced or metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib.…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is confirmed ORR, as assessed by the IRC, per Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the full analysis
set population.
Secondary outcome
Secondary endpoints:
1. Confirmed ORR, as assessed by the investigator, per RECIST version 1.1.
2. DOR as assessed by the investigator and IRC.
3. PFS as assessed by the investigator and IRC.
4. Disease control rate (DCR), defined as best overall response of complete
response (CR), partial response (PR) or stable disease (SD) >=6 weeks by RECIST
version 1.1, as assessed by the investigator and IRC.
5. Time to response as assessed by the investigator and IRC.
6. Confirmed iORR in patients with brain metastases at baseline, as assessed by
the IRC.
7. Duration of intracranial response in patients with brain metastases at
baseline, as assessed by the IRC.
8. Intracranial progression-free survival (iPFS) in patients with brain
metastases at baseline, as assessed by the IRC.
9. OS.
Note: The efficacy endpoints will be analyzed in all treated populations and in
a subgroup of patients who progressed on prior alectinib. Additional details
about subgroup analyses will be provided in the statistical analysis plan (SAP).
10. Safety/tolerability (NCI CTCAE version 4.03).
11. HRQOL assessed with the global health status/quality of life (QOL) and
other function and symptom from EORTC QLQ-C30 (version 3.0), and EORTC
QLQ-LC13.
Background summary
General Information:
This study has been designed by Takeda and is being carried out by doctors at
various hospitals. Takeda is paying for the costs of this study.
For this study 103 patients from different countries are required.
Background of the study and study drug:
Brigatinib is approved by the U.S. Food and Drug Administration (*FDA*), the
regulatory authority in the United States as a treatment for ALK positive
metastatic NSCLC patients (i.e. lung cancer that expresses the ALK abnormal
gene or protein that has spread within the body) who have received prior
treatment with the drug crizotinib. This medicine is not yet approved in your
country. In this study, both you and your doctors and nurses in the study
hospital know what drug you are taking (this is called "open label").
Study objective
Primary Objectives:
To determine the efficacy of brigatinib, as evidenced by confirmed objective
response rate (ORR), in patients with ALK+ locally advanced or metastatic NSCLC
whose disease has progressed on therapy with alectinib or ceritinib.
Secondary Objectives:
1. To characterize the durability of efficacy with brigatinib.
2. To assess intracranial efficacy of brigatinib.
3. To assess the overall survival (OS).
4. To assess the safety and tolerability of brigatinib.
5. To collect plasma concentration-time data for brigatinib to contribute to
population pharmacokinetic analyses.
6. To assess patient-reported symptoms and health-related quality of life
(HRQOL).
Study design
Patients will continue to be treated with brigatinib until they experience
objective disease progression per Response Evaluation Criteria in Solid Tumors
(RECIST) version 1.1, as assessed by the investigator, or intolerable toxicity.
Upon radiological progression, at the discretion of the investigator, patients
who were receiving brigatinib at a dose of 180 mg and have not experienced
toxicity greater than Grade 2 during the treatment may elect to receive
brigatinib at an increased dose of 240 mg QD, or continue study treatment at
the current dose in case they are still benefiting from the treatment at this
dose. In both scenarios, sponsor medical monitor will review and approve the
case.
Intervention
Brigatinib 180 mg QD with a 7-day lead-in at 90 mg QD.
Patients who progressed on brigatinib 180 mg QD dose, did not experience
toxicity Grade >2, and signed a separate informed consent will be given the
option to receive brigatinib at an increased dose of 240 mg QD.
Study burden and risks
Possible side effects and discomforts
Very common (reported in 10% and more of patients) included:
• Pneumonia or infection that occurs in the lung; symptoms may include cough,
shortness of breath, fevers, chills, chest pain, headache, sweating, and
weakness
• Low levels of red blood cell count (which can cause you to feel tired)
• Low levels of white blood cell counts (including white blood cell counts
overall, as well as certain types of white blood cells: lymphocytes and
neutrophils), which could increase the risk of infection
• Activated partial thromboplastin time (APTT) increased (mean a lack of or low
level of one of the blood clotting factors or another substance needed to clot
blood)
• High blood sugar levels
• High insulin levels which may cause low blood sugar, weakness, mental status
changes, and/or weight gain
• Decreased appetite
• Low levels of sodium in the blood
• Low levels of potassium in the blood
• Low levels of magnesium in the blood
• Low levels of phosphate in the blood
• High levels of calcium in the blood
• Headache
• Peripheral neuropathy, a condition in which nerves outside the brain and
spinal cord (peripheral nerves) have been damaged which can result in symptoms
such as numbness, tingling, prickling sensation, weakness or pain
• Dizziness
• Visual Disturbance
• High Blood Pressure
• Cough
• Shortness of breath
• Nausea
• Diarrhoea
• Vomiting
• Constipation
• Abdominal pain
• Stomatitis (inflammation of the lining of any of the structures in the mouth,
including cheeks, gums, tongue, lips, throat and roof or floor of the mouth)
• Increased liver enzymes (Aspartate aminotransferase (AST) increased or
Alanine aminotransferase (ALT) increased) which can suggest damage to
the liver
• Increased lipase level (an enzyme measured in the blood that reflects
function of the pancreas; elevations in lipase may indicate inflammation of the
pancreas)
• Increased amylase level (an enzyme measured in the blood that reflects
function of the pancreas; elevations in amylase may indicate inflammation of
the pancreas)
• Increased alkaline phosphatase level, an enzyme in the blood produced by the
liver and other organs
• Skin rash
• Itchy skin
• Increased creatine phosphokinase level (an enzyme measured in the blood,
elevations may indicate injury or stress to muscle tissue, the heart, or the
brain)
• Muscle pain (including muscle spasms)
• Joint Pain
• Increased creatinine level, which may indicate kidney damage
• Fatigue or tiredness
• Oedema (built up of fluid in the body which causes the affected tissue to
become swollen)
• Fever
Common (reported in 1-9% of patients) included:
• Infection involving the upper respiratory tract; symptoms may include
congestion, sneezing, coughing, fever, and sore throat
• Low platelets or decreased number of blood cells that help to clot blood.
This can be associated with an increased risk of bleeding
• Insomnia or inability to obtain an adequate amount or quality of sleep
• Problems with memory
• Distortion of the sense of taste
• Increased heart rate
• Electrocardiogram QT prolonged (a change in ECG, a study of the electrical
system of the heart that may indicate an increased risk of serious
abnormalities in the heart*s rhythm)
• Slow heart rate
• Noticeably rapid, strong, or irregular heartbeats
• Pneumonitis (inflammation of the lung) or interstitial lung disease (ILD),
diseases that affect the lungs
• Dry Mouth
• Indigestion or upset stomach
• Flatulence or accumulation of gas, usually in excess, that is present in the
intestinal tract and passed out of the body from the rectum
• Increased lactate dehydrogenase (LDH) level, an enzyme present in many body
tissues, especially the heart, liver, kidney, muscles, brain, blood cells, and
lungs. LDH is most often measured to check for tissue damage
• Dry skin
• Increased skin sensitivity to sunlight or lamps
• Musculoskeletal chest pain
• Pain in extremity
• Non*cardiac chest pain
• Pain
• Chest discomfort or pain
• Loss of weight
• High Level of blood cholesterol
Uncommon (reported in less than 1 % of patients) included:
• Muscle and/or bone stiffness
Below you can find more information on the assessments that will be performed
during the course of the research study:
• Informed Consent: Before any study procedures can start, you will need to
read, confirm understanding, and sign this informed consent if you would like
to participate in this study.
• Medical History: A complete medical history, any medications you have used or
are currently using, and any cancer therapies you have had in the past. Please
note that if you do not provide all the information about your medical history,
medicines or supplements you are taking to the study doctor, participating in
this study may harm you. It is important for you to share all information with
your study doctor about how you are feeling and any medicines or supplements
you are taking.
• Physical Exam & Vital Signs: Your blood pressure, heart rate, height, and
weight will be measured. Temperature and breathing rate will also be measured,
if needed. Physical exams will be performed by your study doctor throughout the
study. Some of these exams will be complete physical exams, while others will
be based on the symptoms you are having.
• Eastern Cooperative Oncology Group (ECOG) Status Assessments: Your study
doctor will ask you questions and make health assessments about how your cancer
is affecting your daily life.
• Questionnaires: You will be asked to answer some questions on paper about how
you are feeling and symptoms you might be having.
• Blood Samples: Blood samples will be taken throughout the study.
o Hematology and Chemistry: These blood samples will be used to evaluate your
blood counts and blood chemistry, which will help determine whether your body
reacts well to the study drug and follow-up any risks and discomforts. These
results will also be used to see if you are well enough to continue receiving
the drug. The total amount of blood for these tests is about 15ml or 3teaspoons.
o Pregnancy Tests: If you are a woman and are able to have a baby, a blood or
urine sample will be taken to make sure you are not pregnant within 7 days
before the first dosing then again every 3 cycles and at end of treatment visit.
• Imaging: MRI and/or CT (*CAT scan*). Radiographic scans, which look at the
status of your disease and evaluate your response to the study drug, will be
performed. Your study doctor will determine which type of scan is best to
assess your cancer.
Landsdowne Street 40
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Landsdowne Street 40
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US
Listed location countries
Age
Inclusion criteria
1. Have histologically or cytologically confirmed stage IIIB (locally advanced
or recurrent and not a candidate for curative therapy) or stage IV NSCLC.
2. Must meet both of the following 2 criteria:
a) Have documentation of ALK rearrangement by a positive result from any
laboratory test approved by the Food and Drug Administration (FDA) (eg, the
Vysis ALK Break Apart FISH [fluorescence in situ hybridization] Probe Kit or
the Ventana ALK [D5F3] CDx [companion diagnostic] Assay or Foundation
Medicine*s FoundationOne CDx)
or
Have documented ALK rearrangement by a different test (non-FDA-approved local
lab tests) and have provided tumor sample to the central laboratory (Note:
Central laboratory ALK rearrangement testing results are not required to be
obtained before randomization.)
b) The patient had been treated with any 1 of the ALK tyrosine kinase
inhibitors (TKIs) (alectinib, ceritinib, crizotinib) for at least 12 weeks
before progression.
3. Had progressive disease while on alectinib or ceritinib (defined as no more
than 1 month from last dose of alectinib or ceritinib to disease progression,
as assessed by the investigator or treating physician). (Number of patients not
previously treated with alectinib will be capped at 10 for every 30 patients
enrolled.)
4. Had alectinib or ceritinib as the most recent ALK inhibitor therapy.
Chemotherapy before or after progression on alectinib or ceritinib is allowed.
5. Have at least 1 measurable lesion per RECIST version 1.1 as assessed by the
investigator.
6. Recovered from toxicities related to prior anticancer therapy to National
Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Grade <=1. (Note: Treatment-related alopecia or peripheral neuropathy that are
Grade >1 are allowed if deemed irreversible.)
7. Have Eastern Cooperative Oncology Group performance status <=1.
8. Have adequate organ and hematologic function.
Exclusion criteria
1. Received any prior ALK-targeted TKI other than crizotinib, alectinib, or
ceritinib.
2. Received both alectinib and ceritinib.
3. Received crizotinib, alectinib, or ceritinib within 7 days of the first dose
of brigatinib.
4. Previously received more than 3 regimens of systemic anticancer therapy for
locally advanced or metastatic disease.
Note: A systemic anticancer therapy regimen will be counted if it is
administered for at least 1 complete cycle. A new anticancer agent used as
maintenance therapy will be counted as a new regimen. Neo-adjuvant or adjuvant
systemic anticancer therapy will be counted as a prior regimen if disease
progression/recurrence occurred within 12 months upon completion of this
(neo-)adjuvant therapy.
5. Have symptomatic brain metastasis (parenchymal or leptomeningeal). Patients
with asymptomatic brain metastasis or who have stable symptoms that did not
require an increased dose of corticosteroids to control symptoms in the past 7
days before the first dose of brigatinib may be enrolled.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-000635-27-NL |
| ClinicalTrials.gov | NCT03535740 |
| CCMO | NL66462.078.18 |