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Lung Cancer, Nonsmall CellPhase 3FL-ALTERNCT04028778

Gefitinib in Combination With Anlotinib or Placebo in Previously Untreated EGFR-mutant NSCLC

A Phase 3 study testing Gefitinib and Anlotinib Hydrochloride in people with Lung Cancer, Nonsmall Cell, run by Sun Yat-sen University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Gefitinib is currently the standard-of-care for patients with activating-EGFR mutant advanced non-small cell lung cancer (NSCLC). However, ~30-40% patients are still nonresponsive, and experience significantly varying duration of response and survival rate. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lung Cancer, Nonsmall Cell
What is being tested?
Gefitinib and Anlotinib Hydrochloride
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
310 participants
Where
1 siteChina
Study dates
10 Apr 2019to Dec 2022
Phase
Phase 3
Are there results?
None posted in the registry

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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1.≥ 18 and ≤ 75 years of age
  • 2.Eastern Cooperative Oncology Group(ECOG)performance scale 0 - 1.
  • 3.Life expectancy of more than 3 weeks
  • 4.Histologically confirmed，locally advanced and/or metastatic non-squamous NSCLC of stage IIIB (unsuitable for radiotherapy) or IV or recurrent NSCLC with measurable lesion/ according to RECIST 1.1 which has not received radiotherapy or cryotherapy.
  • 5.Documented evidence of tumor harboring an activating EGFR mutation (exon19 del and L858R)
  • 6.None previous chemotherapy or targeted therapy. NOTE: neoadjuvant and/or adjuvant therapy is allowed which is completed before 6 months
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  • 7.Prior radiation therapy is allowed if: 25% or less of total bone marrow had been irradiated,pelvis and chest had not been irradiated; at least 4 weeks have elapsed from the completion of radiation treatment, and the acute toxicity from radiation treatment had been recover; irradiated lesion is not including measurable lesions unless documented progress after radiation.
  • 8.Adequate hepatic, renal, heart, and hematologic functions (Absolute Neutrophil Count(ANC) ≥ 1.5×109/L, Platelet (PLT) ≥ 100×109/L, Hemoglobin(HB) ≥ 100 g/L, total bilirubin within 1.5×the upper limit of normal(ULN), and serum transaminase≤2.5×the Upper Limit Of Normal(ULN), serum creatine ≤ 1 x Upper Limit Of Normal(ULN), creatinine clearance rate ≥ 50ml/min
  • 9.For women of child-bearing age, the pregnancy test results (serum or urine) within 7 days before enrolment must be negative. They will take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men (previous surgical sterilization accepted), will take appropriate methods for contraception during the study until the 8th week post the last administration of study drug.
  • 10.Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Who cannot join

  • 1.small cell lung cancer (including small cell and non-small cell mixed lung cancer)
  • 2.Symptomatic brain metastases (Patients who have no symptoms and is not needed to receive therapy before 21 days may participate in this trial, but need to be confirmed by MRI\CT or venography that no hematencephalon symptom)
  • 3.Radiologically documented evidence of tumor lesions from large vessels ≤ 5mm or major blood vessel invasion or encasement by cancer; Obvious cavity or necrosis formed in the tumor.
  • 4. hypertensive patients are in the combination therapy of two or more antihypertensive drugs.
  • 5.patients with positive T790M mutation by Gene detection.
  • 6.Patients who suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female ≥ 470 ms). Grade III-IV cardiac insufficiency according to New York Heart Association(NYHA) criteria or echocardiography check: left ventricular ejection fraction (LVEF)<50%;
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  • 7.History of pulmonary interstitial diseases or concurrent pulmonary interstitial diseases.
  • 8.Coagulation disfunction（INR>1.5 or PT>Upper Limit Of Normal(ULN)+4s or Activated Partial Thromboplastin Time (APTT) >1.5 Upper Limit Of Normal(ULN)）, hemorrhagic tendency or receiving the therapy of thrombolysis or anticoagulation
  • 9.Daily hemoptysis up to two teaspoons or more before enrollment
  • 10.History of clinically relevant major bleeding event=<3 months (e.g. gastrointestinal hemorrhage, Hemorrhagic acne， bleeding gastric ulcer, occult blood test ≥ (++), and vasculitis ;
  • 11.Within 12 months before the first treatment occurs artery / venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack(TIA), hematencephalon, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.
  • 12.Known inherited and acquired hemorrhagic and thromboplastic possibility (such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.)
  • 13.Long-term untreated wounds or fractures（in addition to tumor-induced pathological fractures）
  • 14.Within 4 weeks of major surgery and/or injures, fractures , ulceration
  • 15.Significant factors that influence the ingestion and absorption of medicine, (e.g. unable swallow, chronic diarrhea and intestinal obstruction);
  • 16.History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months.
  • 17.Urine protein≥++, and 24h urine protein quantitation≥1.0g;
  • 18.Symptomatic serous effusion requiring treatment .(including hydrothorax, ascites, hydropericardium);
  • 19.Active infection need antimicrobial treatments（such as antibiotics and antiviral drugs should be used, excluding anti-hepatitis B treatment and antifungal therapy. ）
  • 20.History of psychiatric drugs abuse and not be abstinent, or dysphrenia
  • 21.Less than 4 weeks from the last clinical trial
  • 22.History or concomitant other malignancy except cured basal cell skin cancer, or carcinoma in situ of the cervix, or superficial bladder cancer;
  • 23.Administration of strong/potent cytochrome P450 (CYP)3A4 inhibitors within 7 days, or inducers within 12 days;
  • 24.Pregnant or breastfeeding women；patients who have fertility are unwilling or unable to take effective contraceptive measures;
  • 25.Other conditions regimented at investigators' discretion

Trial locations and contacts

1 site in 1 country.

Wenfeng Fang, MD contact

020-87343822

fangwf@sysucc.org.cn

China1 site, 1 recruiting

  • Cancer Center of Sun Yat-Sen University (CCSU)

    Guangzhou, Guangdong

    Li Zhang, MD, 86-20-87343458, zhangli6@mail.sysu.edu.cn

    Li Zhang, MD

    Recruiting

Other trials in China

About this study

Official title: A Multicenter, Randomized, Double-Blind Study of Gefitinib in Combination With Anlotinib or Placebo in Previously Untreated Patients With EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer

Gefitinib is currently the standard-of-care for patients with activating-EGFR mutant advanced non-small cell lung cancer (NSCLC). However, ~30-40% patients are still nonresponsive, and experience significantly varying duration of response and survival rate. Anlotinib is an efficient multi-target tyrosine kinase inhibitor (TKI) that effectively block the migration and proliferation of endothelial cells and reduce tumor microvascular density by targeting VEGFRs, FGFRs, PDGFRs. It has been proved to be safe and effective in advanced lung cancer after second-line standard chemotherapy failure, which can significantly extend the survival of patients and approves as a third-line treatment for advanced NSCLC. Here, we prepared to evaluate whether the combination of gefitinb and anlotinib can preferably improved survival of untreated NSCLC with EGFR activating mutation.

Being tested
Gefitinib, Anlotinib Hydrochloride, Placebo
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.

  • GefitinibDrug

    Also called Iressa

    Gefitinib 250mg, p.o., qd, D1-D21; 3 weeks one cycle.

  • Anlotinib HydrochlorideDrug

    Anlotinib hydrochloride capsule 12mg, p.o., qd, D1-D14; 3 weeks one cycle.

  • PlaceboOther

    Placebo simulating anlotinib hydrochloride capsule 12mg, p.o., qd, D1-D14; 3 weeks one cycle.

Study groups in NCT04028778
Study groupRoleWhat they receive
Gefitinib + AnlotinibExperimentalPatients will be treated with Gefitinib 250mg, p.o., qd and anlotinib hydrochloride capsule 12mg, p.o., qd, D1-D14; take on an empty stomach (take at the same time every day as possible), every 3 weeks for a cycle.
Receives: Drug: Gefitinib; Drug: Anlotinib Hydrochloride
Gefitinib + PlaceboPlacebo comparatorPatients will be treated with Gefitinib 250mg, p.o., qd and placebo to simulate anlotinib hydrochloride capsule 12mg, p.o., qd, D1-D14; take on an empty stomach (take at the same time every day as possible), every 3 weeks for a cycle
Receives: Drug: Gefitinib; Other: Placebo

What is being measured

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

  1. Progress-free survival (PFS)

    Progression-Free Survival (PFS) as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)

    Measured: Approximately 2 Years

Secondary outcomes (4)

  1. Overall Survival (OS)

    OS was defined as the time from the date of randomization to the date of death due to any cause.

    Measured: Approximately 5 Years

  2. Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]), as Assessed Using RECIST v.1.1

    PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).

    Measured: Approximately 2 Years

  3. Percentage of Participants With Clinical Benefit, as Assessed According to RECIST v1.1

    Clinical benefit was defined as objective response (PR+CR), or no disease progression lasting for more than or equal to (>/=) 24 weeks since randomization. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

    Measured: Approximately 2 Years

  4. Duration of Objective Response, as Assessed by Investigator Using RECIST v1.1

    Duration of objective response: the time from the first tumor assessment that supported the participant's objective response (CR or PR, whichever was first recorded) to first documented disease progression or death due to any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

    Measured: Approximately 2 Years

Timeline

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

  1. First posted23 Jul 2019
  2. Study start10 Apr 2019
  3. Primary completionDec 2020 (estimated)
  4. Study completionDec 2022 (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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multicenter, Randomized, Double-Blind Study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
310 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04028778
Sponsor's protocol ID
2018-FXY-134-内科
Acronym
FL-ALTER
Status last verified
Nov 2019
First submitted
11 Jul 2019
Last updated
8 Nov 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Zhou HQ, Zhang YX, Chen G, Yu QT, Zhang H, Wu GW, Wu D, Lin YC, Zhu JF, Chen JH, Hu XH, Lan B, Zhou ZQ, Lin HF, Wang ZB, Lei XL, Pan SM, Chen LM, Zhang J, Kong TD, Yao JC, Zheng X, Li F, Zhang L, Fang WF. Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial. Signal Transduct Target Ther. 2024 Aug 13;9(1):215. doi: 10.1038/s41392-024-01927-9.

    PubMed 39134529

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gefitinib and Anlotinib Hydrochloride in people with Lung Cancer, Nonsmall Cell, run by Sun Yat-sen 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 10 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 8 Nov 2019. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Wenfeng Fang, MD (020-87343822, fangwf@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progress-free survival (PFS) (time frame: Approximately 2 Years). 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 NCT04028778, which also lists 1 linked publication.

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 8 Nov 2019.

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