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Non-small Cell Lung CancerPhase 1/2NCT05777278

Savolitinib Plus Docetaxel as 2L in EGFR/ALK/ROS1/MET ex14m-wildtype NSCLC With MET Overexpression

A Phase 1/2 study testing Savolitinib and Docetaxel in people with Non-small Cell Lung Cancer, run by The First Affiliated Hospital of Guangzhou Medical University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Savolitinib and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteChina
Study dates
26 Jul 2023to 31 Aug 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
  • Female or males age ≥18 years at the time of signing the ICF.
  • Histologically or cytologically confirmed locally advanced or metastatic EGFR/ALK/ROS1/MET ex14m-wildtype NSCLC.
  • Has only received first line systemic treatment of non-targeted advanced NSCLC.
  • Prior MET inhibitor therapy is not allowed.
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  • At least 28 days since last treatment.
  • MET overexpression as determined IHC on tumor tissue.
  • MET overexpression by IHC, 3+ in ≥50% of tumor cells
  • Local IHC results are acceptable.
  • 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.
  • 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.
  • 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)
  • 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
  • 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.
  • 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.
  • Patients with known tumor thrombus or deep vein thrombosis are eligible if clinically stable on low molecular weight heparin (LMWH) for ≥2 weeks.
  • Ability to swallow and retain oral medications.
  • Willingness and ability to comply with study and follow-up procedures.
  • 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.
  • 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.

Who cannot join

  • 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).
  • 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
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  • Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy).
  • 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.
  • 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.
  • Serious underlying medical condition at the time of treatment that would impair the ability of the patient to receive protocol treatment.
  • 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.
  • Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Past medical history of ILD/pneumonitis, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
  • Known serious active infection including, but not limited to, tuberculosis, or human immunodeficiency virus (positive human immunodeficiency virus 1/2 antibodies).
  • 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
  • Known contraindications to docetaxel administration.
  • Known hypersensitivity to the active or inactive excipients of docetaxel or savolitinib or drugs with a similar chemical structure or class.
  • Women who are either pregnant or breast-feeding.
  • Patients with previous medical history of Stevens Johnson syndrome (SJS) and serious cutaneous toxicity.
  • Prior exposure to HGF/MET inhibitors, e.g., foretinib, crizotinib, cabozantinib, merestinib, onartuzumab, capmatinib, tepotinib, etc.
  • 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).
  • 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.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  • 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.
  • For women only-Currently breastfeeding.
  • Previous enrolments in the present study.
  • Without civil capacity or with restricted civil capacity.
  • Any other reasons judged by the leading investigator to prevent the subject from participating in this study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jianxing He, M.D contact

+86-20-83337792

drjianxing.he@gmail.com

Wenhua Liang, M.D contact

+86-13710249454

liangwh1987@163.com

China1 site, 1 recruiting

  • Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University

    Guangzhou, Guangdong

    Wenhua Liang, M.D, +86-13710249454, liangwh1987@163.com

    Wenhua Liang, M.D

    Recruiting

Other trials in China

About this study

Official title: A Prospective Study of Savolitinib Plus Docetaxel in Pretreated EGFR/ALK/ROS1/MET ex14m-wildtype Advanced NSCLC Patients With MET Overexpression (FirstMET)

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.

Being tested
Savolitinib, Docetaxel
Keywords
Savolitinib, Docetaxel, MET Overexpression, Advanced NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SavolitinibDrug

    Savolitinib (300mg or 200mg according to safety run-in recommendation, p.o., BID)

  • DocetaxelDrug

    Docetaxel (60 mg/m2, ivgtt, q3w)

Study groups in NCT05777278
Study groupRoleWhat they receive
Savolitinib Plus DocetaxelExperimentalSingle Arm
Receives: Drug: Savolitinib; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ORR (Objective Response Rate)

    ORR (Objective Response Rate) is defined as the proportion of participants who confirmed CR (Complete Response) or PR (Partial response) as their best overall response based on Response Evaluation Criteria in Solid Tumors (RECIST)1.1 as assessed by the investigator.

    Measured: The analysis will occur at 12 weeks after last patient in.

Secondary outcomes (4)

  1. PFS (Progression-Free Survival)

    PFS (Progression-Free Survival) is defined as the time from the first dose of study intervention until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression.

    Measured: The analysis will occur when 70% data maturity of PFS events (14 PFS events) is observed in each cohort, at approximately 9 months after last patient in.

  2. DoR (Duration of Response)

    DoR (Duration of Response) is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression (ie, date of PFS (Progression-Free Survival) event or censoring-date of first response+1).

    Measured: The analysis will occur when 70% data maturity of PFS events (14 PFS events) is observed in each cohort, at approximately 9 months after last patient in.

  3. DCR (Disease Control Rate)

    DCR (Disease Control Rate) is defined as the number(percent)of subjects with at least one visit response of confirmed CR (Complete Response), PR (Partial Response) or SD (Stable Disease), based on Investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

    Measured: The analysis will occur at 12 weeks after last patient in.

  4. OS (Overall Survival)

    OS (Overall Survival) is defined as the time from the start of treatment until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

    Measured: The analysis will occur when 70% data maturity of PFS events (14 PFS events) is observed in each cohort, at approximately 9 months after last subject in, up to a maximum of approximately 3 years after first subject in.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2023
  2. Study start26 Jul 2023
  3. Primary completion31 Aug 2027 (estimated)
  4. Study completion31 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Clinical trials with a single arm
Masking
None (open label)
Enrolment
29 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05777278
Sponsor's protocol ID
FirstMET (ESR-22-21748)
Status last verified
Oct 2023
First submitted
21 Feb 2023
Last updated
10 Oct 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Savolitinib and Docetaxel in people with Non-small Cell Lung Cancer, run by The First Affiliated Hospital of Guangzhou Medical University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jianxing He, M.D (+86-20-83337792, drjianxing.he@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ORR (Objective Response Rate) (time frame: The analysis will occur at 12 weeks after last patient in.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05777278.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2023.

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