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Non Small Cell Lung CancerPhase 2ALTN-03NCT04029350

Study of Anlotinib Combined With Osimertinib as Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M

A Phase 2 study testing Anlotinib Combined With Osimertinib in people with Non Small Cell Lung Cancer, run by Tianjin Medical University Cancer Institute and Hospital at 4 sites 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 The sponsor has not verified this record for over two years, so it may be out of date.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
Search all trials

Trial summary

Evaluate the efficacy and safety of Anlotinib combined with Icotinib as the second-line treatment in stage IIIb-IV NSCLC patients with sensitive EGFR and T790M mutations. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Anlotinib Combined With Osimertinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
4 sitesChina
Study dates
31 Jul 2019to 30 Nov 2021
Phase
Phase 2
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

  • Histologically or cytologically confirmed, locally advanced and/or metastatic IIIB, IIIC or IV non-squamous NSCLC or recurrent non-squamous NSCLC (according to the 8th Edition of the AJCC Staging system).
  • Non-small cell lung cancer (NSCLC) with an activating EGFR mutation (exon 19 deletion, L858R point mutation, or any other mutation known to be associated with EGFR TKI sensitivity); presence of an activating EGFR mutation may be documented in tumor tissue or by plasma testing.
  • Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating tumour DNA, documented in tissue, plasma or serum after disease progression on the most recent first- or second-generation EGFR TK treatment regimen.
  • 18-75years，ECOG PS：0-2，Life expectancy of more than 3 months，with measurable lesion ( RECIST1.1).
  • ≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction；Previously received radiation therapy, but the radiotherapy area must be <25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment.
  • Main organs function is normal.
  • Signed and dated informed consent.
  • The woman patients of childbearing age must agree to take contraceptive methods during the research and within another 8 weeks after treatment. Pregnancy test (blood serum test or urine) should be done within 7 days before the research and the result should be negative.The man patients who must agree to take contraceptive methods during the research and within another 8 weeks after treatment.

Who cannot join

  • Squamous cell carcinoma (including adenosquamous carcinoma); Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
  • Non-small cell lung cancer (NSCLC) with an EGFR C797S mutation.
  • Prior treatment with a third-generation EGFR TKI (i.e. Rociletinib, Olmutinib、BPI-15086、BPI-7711、Osimertinib); Prior treatment with agents targeting the VEGF pathway, including bevacizumab and Anlotinib.
  • Treatment with an EGFR TKI (i.e. erlotinib, gefitinib or afatinib) within 8 days or approximately 5 x half-life, whichever is longer, of the first dose of study treatment；Patients may not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within five half-lives of the compound or 3 months, whichever is greater
  • Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 platinum-therapy related neuropathy
  • Any factor that would preclude adequate absorption of Osimertinib and Anlotinib, including refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection
Show all 25Show fewer
  • Patients with obvious brain metastases, cancerous meningitis, spinal cord compression, or with brain or pia mater disease. (patient with brain metastases who have completed treatment 28 days before and the symptoms are stable can be Enrolled, also should have no cerebral hemorrhage symptoms confirmed by brain MRI, CT or venography evaluation
  • Patients who planned to receive systemic anti-tumor therapy within 4 weeks prior to allocation or during the course of this study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or receiving the Mitomycin C 6 weeks prior to medication). Extra-field radiotherapy (EF-RT) was performed 4 weeks prior to allocation or restricted radiotherapy for assessing tumor lesions within 2 weeks prior to allocation
  • Patients with any severe and/or uncontrolled disease, including:
  • Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] > 140 mmHg and/or diastolic blood pressure [DBP] > 90 mmHg despite antihypertensive medication)
  • Mean resting corrected QT interval (Fridericia's correction formula [QTcF]) > 470 ms ms obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived corrected QT (QTc) value; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block); Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval;
  • Active or uncontrollable serious infection (≥CTC AE Level 2 infection)
  • Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis need to be treated with antiretroviral therapy
  • Poor control of diabetes (fasting blood glucose [FBG]> 10 mmol/L)
  • Urine routine test protein ≥++, and confirmed 24 hours urine protein> 1.0 g
  • Long-term unhealed wounds or fractures
  • Evidence of bleeding diathesis or coagulopathy (including clinically significant hemoptysis)
  • Patients with artery/venous thrombotic occurred within 12 months before allocation, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis and pulmonary embolism
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
  • Patients with a history of psychotropic medicine abuse and cannot quit or have mental disorders
  • Respiratory syndrome (dyspnea≥CTC AE 2), severe pleural effusion, ascites, pericardial effusion
  • History of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or history of organ transplantation; active infection including hepatitis B (HBV DNA level ≥1000 copies /mL), hepatitis C and human immunodeficiency virus (HIV)
  • Has a history of malignant tumors. Except for patients with cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma or orthotopic cervical cancer who have undergone curative treatment and have no disease recurrence within 5 years after the start of treatment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD9291 (osimertinib) or Anlotinib
  • Patient was diagnosed with disease which will severely endanger the security of patients or influence the completion of this research; Judgment by the investigator that should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Trial locations and contacts

4 sites in 1 country.

China4 sites

  • Fourth Hospital of Hebei Medical University

    Shijiazhuang, Hebei

  • Hebei Provincial People's Hospital

    Shijiazhuang, Hebei

  • Shanxi Provincal Cancer Hospital

    Taiyuan, Shanxi

  • Tianjin Medical University Cancer Institute and Hospital

    Tianjin, Tianjin Municipality, 300060

Other trials in China

About this study

Official title: A Multi-center, One-arm, Phase II Trial of Anlotinib Combined With Osimertinib as the Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M.

Evaluate the efficacy and safety of Anlotinib combined with Icotinib as the second-line treatment in stage IIIb-IV NSCLC patients with sensitive EGFR and T790M mutations.

Read the detailed description

Anlotinib Hydrochloride is a kind of innovative medicines approved by State Food and Drug Administration（CFDA:2011L00661） which was developed by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd. Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β and c-Kit.

Being tested
Anlotinib Combined With Osimertinib
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.

  • Anlotinib Combined With OsimertinibDrug

    Also called A+T

    Anlotinib：12mg/capsule, take once when limosis in the morning. If patients suffer from AEs, they can get declined dosage (10mg or 8mg).

    Osimertinib：80 mg/tablet， per os (p.o.) daily. It should be continued until disease progression or intolerable toxicity or patients withdraw of consent.

Study groups in NCT04029350
Study groupRoleWhat they receive
Anlotinib Combined With OsimertinibExperimentalAnlotinib 12 mg once a day from day 1 to 14 of a 21-day cycle. Osimertinib 80mg p.o, qd. It should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent.
Receives: Drug: Anlotinib Combined With Osimertinib

What is being measured

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

  1. Progression-free survival (PFS)

    The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"

    Measured: each 42 days up to PD or death (up to 24 months)

Secondary outcomes (4)

  1. OS（Overall Survival）

    OS was defined as time from date of enrollment to date of death due to any cause. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive.

    Measured: up to 24 months

  2. ORR（Objective Response Rate）

    To evaluate the effectiveness of Anlotinib Hydrochloric Capsule Plus Icotinib Hydrochloric Tablet by enhanced CT/MRI scan every two cycles. Objective Response Rate (ORR) is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients.

    Measured: each 42 days up to intolerance the toxicity or PD (up to 24 months)

  3. DCR（Disease Control Rate）

    To evaluate the effectiveness of Anlotinib Hydrochloric Capsule Plus Icotinib Hydrochloric Tablet by enhanced CT/MRI scan every two cycles. Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease).

    Measured: each 42 days up to intolerance the toxicity or PD (up to 24 months)

  4. Adverse Events

    Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Measured: Until 30 day safety follow-up visit

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 start31 Jul 2019
  3. Primary completion31 Jan 2020 (estimated)
  4. Study completion30 Nov 2021 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04029350
Sponsor's protocol ID
ALTN-03-II-01
Acronym
ALTN-03
Status last verified
Jun 2019
First submitted
21 Jul 2019
Last updated
21 Aug 2019
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: De-identified individul participant data for all primary and secondary outcome measures will be made available.

Publications

  • Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.

    PubMed 27959700

  • Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1569-1575. doi: 10.1001/jamaoncol.2018.3039.

    PubMed 30098152

  • Akamatsu H, Teraoka S, Morita S, Katakami N, Tachihara M, Daga H, Yamamoto N, Nakagawa K. Phase I/II Study of Osimertinib With Bevacizumab in EGFR-mutated, T790M-positive Patients With Progressed EGFR-TKIs: West Japan Oncology Group 8715L (WJOG8715L). Clin Lung Cancer. 2019 Jul;20(4):e492-e494. doi: 10.1016/j.cllc.2019.03.002. Epub 2019 Mar 19.

    PubMed 31085043

  • Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. doi: 10.1016/S1470-2045(19)30035-X. Epub 2019 Apr 8.

    PubMed 30975627

  • Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27.

    PubMed 25175099

  • Wang X, Li Z, Wang L, Liang Y, Huang C, Chen P, Huang D, Song X, Ding C, Wang C, Jiang R. Osimertinib plus anlotinib for advanced NSCLC with acquired EGFR T790M mutation: results from a multicenter phase II study with ctDNA analysis. BMC Med. 2025 Apr 15;23(1):223. doi: 10.1186/s12916-025-04044-8.

    PubMed 40234867

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anlotinib Combined With Osimertinib in people with Non Small Cell Lung Cancer, run by Tianjin Medical University Cancer Institute and Hospital at 4 sites 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 8 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 21 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 phase mean?

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?

Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: each 42 days up to PD or death (up to 24 months)). 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 NCT04029350, which also lists 6 linked publications.

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 21 Aug 2019.

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