Trial Title:
Savolitinib Plus Docetaxel as 2L in EGFR/ALK/ROS1/MET ex14m-wildtype NSCLC With MET Overexpression
NCT ID:
NCT05777278
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Docetaxel
Conditions: Keywords:
Savolitinib
Docetaxel
MET Overexpression
Advanced NSCLC
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Clinical trials with a single arm
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Savolitinib
Description:
Savolitinib (300mg or 200mg according to safety run-in recommendation, p.o., BID)
Arm group label:
Savolitinib Plus Docetaxel
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Docetaxel (60 mg/m2, ivgtt, q3w)
Arm group label:
Savolitinib Plus Docetaxel
Summary:
This is a prospective, pilot, single-arm, single-center study exploring the efficacy and
safety of savolitinib plus docetaxel as second-line therapy in patients with MET
overexpressed, EGFR/ALK/ROS1/MET ex14m-wildtype advanced NSCLC.
Participants will receive treatment of docetaxel (60 mg/m2, ivgtt, q3w) in combination
with savolitinib (300mg or 200mg according to safety run-in recommendation, p.o., BID)
after informed consent signed. Treatment will continue until either objective disease
progression, unacceptable toxicity occurs, consent is withdrawn, other discontinuation
criterion is met, or study completion.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol.
2. Provision of signed and dated, written ICF prior to any mandatory study specific
procedures, sampling, and analyses.
3. Female or males age ≥18 years at the time of signing the ICF.
4. Histologically or cytologically confirmed locally advanced or metastatic
EGFR/ALK/ROS1/MET ex14m-wildtype NSCLC.
5. Has only received first line systemic treatment of non-targeted advanced NSCLC.
- Prior MET inhibitor therapy is not allowed.
- At least 28 days since last treatment.
6. MET overexpression as determined IHC on tumor tissue.
- MET overexpression by IHC, 3+ in ≥50% of tumor cells
- Local IHC results are acceptable.
7. WHO or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with
no deterioration over the previous 2 weeks prior to baseline or day of first dosing
and a minimum life expectancy of 12 weeks.
8. At least 1 lesion that can be accurately measured at baseline as ≥10 mm in the
longest diameter (except lymph nodes, which must have short axis ≥15 mm) with
computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for
accurate repeated measurements.
9. Adequate haematological function defined as:
- Haemoglobin ≥9 g/dL (no transfusion in the past 2 weeks).
- Absolute neutrophil count ≥1.5×10^9/L.
- Platelet count ≥100,000/μL (no transfusion in the past 10 days)
10. Adequate liver function defined as:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the
upper limit of normal (ULN) with total bilirubin (TBL) ≤ ULN
- OR TBL >ULN to ≤1.5x ULN with ALT and AST ≤ ULN, alkaline phosphatase (ALP) ≤
2.5x ULN
11. Adequate renal function defined as a serum creatinine <1.5 times the institutional
ULN OR a glomerular filtration rate ≥50 mL/min, as assessed using the standard
methodology at the investigating centre (eg, Cockcroft-Gault, Modification of Diet
in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration formulae,
ethylenediaminetetraacetic acid clearance or 24-hour urine collection). Confirmation
of creatinine clearance is only required when creatinine is >1.5 times ULN.
12. Adequate coagulation parameters, defined as:
-International Normalisation Ratio (INR) <1.5 and activated partial thromboplastin
time <1.5 x ULN unless patients are receiving therapeutic anti coagulation which
affects these parameters.
13. Patients with known tumor thrombus or deep vein thrombosis are eligible if
clinically stable on low molecular weight heparin (LMWH) for ≥2 weeks.
14. Ability to swallow and retain oral medications.
15. Willingness and ability to comply with study and follow-up procedures.
16. Females of childbearing potential should be willing to use highly effective
contraceptive measures, should not be breast feeding, and must have a negative
pregnancy test if of childbearing potential or must have evidence of
non-childbearing potential by fulfilling one of the following criteria at screening:
Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least
12 months following cessation of all exogenous hormonal treatments; women under the
age of 50 years would be considered postmenopausal if they have been amenorrhoeic
for 12 months or more following cessation of exogenous hormonal treatments and with
LH and FSH levels in the post-menopausal range for the institution; or women with
documentation of irreversible surgical sterilisation by hysterectomy, bilateral
oophorectomy or bilateral salpingectomy.
17. Male patients with a female partner of childbearing potential should be willing to
use barrier contraception during the study and for 6 months following
discontinuation of study drug. Patients should refrain from donating sperm from the
start of dosing until 6 months after discontinuing study treatment.
Exclusion Criteria:
1. As judged by the investigator, active gastrointestinal disease or other condition
that will interfere significantly with the absorption, distribution, metabolism, or
excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting,
diarrhoea Grade ≥2, and malabsorption syndrome).
2. Any of the following cardiac diseases currently or within the last 6 months:
- Unstable angina pectoris
- Congestive heart failure (New York Heart Association [NYHA] ≥Grade 2)
- Acute myocardial infarction
- Stroke or transient ischemic attack
3. Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy).
4. Mean resting correct QT interval (QTcF) >470 msec for women and >450 msec for men on
screening obtained from 3 electrocardiograms (ECGs) or factors that may increase the
risk of QTcF prolongation such as chronic hypokalaemia not correctable with
supplements, congenital or familial long QT syndrome, or family history of
unexplained sudden death under 40 years of age in first-degree relatives or any
concomitant medication known to prolong the QT interval and cause Torsade de
Pointes.
5. Any clinically important abnormalities in rhythm, conduction or morphology of
resting electrocardiograms (ECGs), e.g. complete left bundle branch block, third
degree heart block, second degree heart block, PR interval >250 msec.
6. Serious underlying medical condition at the time of treatment that would impair the
ability of the patient to receive protocol treatment.
7. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89)
administered ≤28 days or limited field radiation for palliation ≤7 days prior to
starting study drug or has not recovered from side effects of such therapy.
8. Major surgical procedures ≤28 days of beginning study drug or minor surgical
procedures ≤7 days. No waiting is required following port-a-cath placement.
9. As judged by the investigator, any evidence of severe or uncontrolled systemic
diseases, including renal transplant, active bleeding diatheses or uncontrolled
hypertension, which in the investigator's opinion makes it undesirable for the
patient to participate in the trial or which would jeopardise compliance with the
protocol.
10. Active hepatitis B (HBV) (positive HBV surface antigen [HBsAg] result) or hepatitis
C (HCV). Patients with a past or resolved HBV or HCV infection are eligible if:
- Negative for HBsAg and positive for hepatitis B core antibody [anti-HBc] or
- Positive for HBsAg, but for >6 months have had normal transaminases and HBV DNA
levels between 0 to 2000 IU/mL (inactive carrier state) and willing to start
and maintain antiviral treatment for at least the duration of the study.
- Patients with a past or resolved HBV infection must have monthly monitoring of
ALT and HBV DNA
- HBV DNA levels >2000 IU/mL but on prophylactic antiviral treatment for the past
3 months and will maintain the antiviral treatment during the study.
- Patients with positive HCV antibody are eligible only if the polymerase chain
reaction is negative for HCV ribonucleic acid.
11. Presence of other active cancers, or history of treatment for invasive cancer,
within the last 5 years. Patients with Stage I cancer who have received definitive
local treatment at least 3 years previously and are considered unlikely to recur are
eligible. All patients with previously treated in situ carcinoma (ie, non-invasive)
are eligible, as are patients with history of non-melanoma skin cancer.
12. Unresolved toxicities from any prior therapy greater than Common Terminology
Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study
treatment/randomization with the exception of alopecia.
13. Spinal cord compression or brain metastases unless asymptomatic, stable, and not
requiring steroids for at least 2 weeks prior to start of study intervention.
Subjects with leptomeningeal metastases are ineligible.
14. Past medical history of ILD/pneumonitis, drug-induced ILD, radiation pneumonitis
which required steroid treatment, or any evidence of clinically active ILD.
15. Known serious active infection including, but not limited to, tuberculosis, or human
immunodeficiency virus (positive human immunodeficiency virus 1/2 antibodies).
16. History of liver cirrhosis of any origin and clinical stage; or history of other
serious liver disease or chronic disease with relevant liver involvement, with or
without normal LFTs, such as
- Hemochromatosis
- Alpha-1 Antitrypsin deficiency
- Autoimmune hepatitis (AIH)
- Primary sclerosing cholangitis (PSC)
- Primary biliary cirrhosis (PBC)
- Biopsy-confirmed Non-Alcoholic Steatohepatitis (NASH) with advanced fibrosis
- Biopsy- confirmed Alcoholic Steatohepatitis with advanced fibrosis
- Wilson's disease
- Hepatocellular carcinoma
17. Known contraindications to docetaxel administration.
18. Known hypersensitivity to the active or inactive excipients of docetaxel or
savolitinib or drugs with a similar chemical structure or class.
19. Women who are either pregnant or breast-feeding.
20. Patients with previous medical history of Stevens Johnson syndrome (SJS) and serious
cutaneous toxicity.
21. Prior exposure to HGF/MET inhibitors, e.g., foretinib, crizotinib, cabozantinib,
merestinib, onartuzumab, capmatinib, tepotinib, etc.
22. Patients currently receiving (or unable to stop use prior to receiving the first
dose of study treatment) medications or herbal supplements known to be strong
inducers of CYP3A4, strong inhibitors of CYP1A2, within 2 weeks of the first dose of
study treatment will be excluded. Herbal preparations/medications are not allowed
throughout the study. These herbal medications include, but are not limited to: St.
John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA),
yohimbe, saw palmetto, and ginseng. Patients should stop using these herbal
medications 7 days prior to first dose of study drug (three weeks for St John's
wort). All patients must try to avoid concomitant use of any medications, herbal
supplements and/or ingestion of foods with known inducer effects on CYP3A4 during
the study and for 3 months later the last dose intake (detailed description in
Appendix G).
23. Participation in another clinical study with a study interventional medication
administered within five half-lives of the compound or 3 months, whichever is
greater or investigational medicinal device administered in the last 30 days prior
to randomisation/first dose of study intervention or concurrent enrolment in another
clinical study, unless it is an observational (non-interventional) clinical study or
during the follow-up period of an interventional study.
24. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).
25. Judgment by the investigator that the participant should not participate in the
study if the participant is unlikely to comply with study procedures, restrictions
and requirements.
26. For women only-Currently breastfeeding.
27. Previous enrolments in the present study.
28. Without civil capacity or with restricted civil capacity.
29. Any other reasons judged by the leading investigator to prevent the subject from
participating in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Wenhua Liang, M.D
Phone:
+86-13710249454
Email:
liangwh1987@163.com
Contact backup:
Last name:
Wenhua Liang, M.D
Start date:
July 26, 2023
Completion date:
August 31, 2027
Lead sponsor:
Agency:
The First Affiliated Hospital of Guangzhou Medical University
Agency class:
Other
Source:
The First Affiliated Hospital of Guangzhou Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05777278
