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Lung Cancer MetastaticPhase 1/2NCT03706287

Efficacy and Safety of Anlotinib Plus Platinum Plus Pemetrexed in T790M-negative NSCLC

A Phase 1/2 study testing anlotinib 8mg + AP/PC, anlotinib 10mg + AP/PC and anlotinib 12mg + AP/PC in people with Lung Cancer Metastatic, run by Sichuan Cancer Hospital and Research Institute at 6 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 The sponsor has not verified this record for over two years, so it may be out of date.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
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Trial summary

This study is conducted to explore the safety and efficacy of anlotinib, a tyrosine kinase inhibitors of vascular endothelial growth factor receptor 2（VEGFR）、FGFR（fibroblast growth factor receptor）, platelet-derived growth factor receptor（PDGFR） and tumor cell proliferation related kinase c-Kit, combined with platinum… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lung Cancer Metastatic
What is being tested?
anlotinib 8mg + AP/PC, anlotinib 10mg + AP/PC and anlotinib 12mg + AP/PC
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
6 sitesChina
Study dates
6 Dec 2018to 10 Mar 2021
Phase
Phase 1/2
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

  • ≥ 18 and ≤ 75 years of age. Signed the informed consent form prior to patient entry
  • Histologically or pathologically confirmed non-squamous non-small cell lung cancer(NSCLC) with stage IV .
  • Epidermal Growth Factor Receptor(EGFR)mutations confirmed by molecular detection (including, but not limited to 19 exon deletion and L858R) external pathological examination was accepted (including pathological or blood test results)
  • Patients have only be treated with EGFR -TKIs（Tyrosine kinase inhibitors）including gefitinib, elotinib or icotinib, and received a best response of PR for ≥4months or SD for 6 months; disease has progressed recently according to RECIST 1.1 and negative for T790M detection（detection methods including ddPCR、ARMS or NGS） (For recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment）
  • Must have at least one measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter imaged by CT scan or MRI；prior topical treatment, such as radiotherapy cryosurgery to the lesions is not allowed in less than 3 months;
  • Life expectancy ≥3 months.
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  • Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
  • Toxicity caused by prior anti-cancer treatments was restored to ≤ level 1 in CTC AE (4.0) , except alopecia;
  • The blood routine examination need to be standard (no blood transfusion and blood products within 14 days, no g-csf and other hematopoietic stimulating factor correction) Hemoglobin（HB）≥90 g/L A Neutrophil count of （ANC）≥1.5×109/L A Platelet count of （PLT）≥80×109/L A Total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL) A alanine aminotransferase (ALT) and a aspartate aminotransferase (AST) of ≤2.5 UNL, in case of liver metastasis ALAT and ASAT≤5 UNL A creatinine (Cr) of ≤1.5 UNL; a creatinine clearance rate ≥ 60ml/min (Cockcroft-Gault)
  • The woman patients of childbearing age who must agree to take contraceptive methods during the research and within another 8 weeks after it and examined as negative in blood serum test or urine pregnancy test within 7 days before the research; the man patients who must agree to take contraceptive methods during the research and within another 8 weeks;
  • Voluntarily joined the study and signed informed consent, with good compliance and follow-up.

Who cannot join

  • Small Cell Lung Cancer mixed or squamous mixed;
  • No squamous NSCLC with hemoptysis (>50ml/day);
  • Symptomatic brain metastases after treatment;
  • Tumor locate within a distance of less than 5 mm from the large vessels, less than 2 cm from the bronchial tree, or has invaded local large vessels; tumor with cavum or necrotic obviously;
  • Uncontrolled hypertension (systolic ≥150mmHg and/or diastolic ≥100mmHg, despite optimal drug therapy).
  • Patients with with grade Ⅱ myocardial ischemia or myocardial infarction, poor control of arrhythmias (including QTc interval male ≥ 450 ms, female ≥470 ms); according to NYHA standard, grade Ⅲ ~ Ⅳ heart failure, or cardiac color Doppler ultrasound examination showed left ventricular ejection fraction (LVEF) <50%.
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  • Coagulation dysfunction (INR> 1.5, PT> ULN +4s or APTT> 1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment;note: Note: under the premise of International Normalized ratio (INR) of prothrombin time (PT) Less than or equal to 1.5, allow to administrate low-dose heparin (adult daily dose is 06000 ~ 12000 U) or low-dose aspirin (100 mg daily dosage or less) , for prophylactic purposes
  • Patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g.
  • Patients whose has peripheral neuropathy over level 2 in CTC AE4.0, except trauma.
  • Patients with respiratory syndrome (difficulty breathing of level 2 or higher ), serous cavity effusion need to surgical treatment ( including pleural of level 2 or higher with respiratory distress and anoxia
  • Patients who have unhealed wounds or fractures for a long time.
  • Patients with severe infections , and need to receive systemic antibiotic treatment
  • Decompensated diabetes or other contraindication with high dose glucocorticoid therapy;
  • Cirrhosis or decompensated liver disease; active or untreated hepatitis C and/or Hepatitis B virus (HBV) infection（prior hepatitis B history, HBsAg positive and HBV DNA≥500IU/mL; HCV RNA positive and hepatic Insufficiency
  • History of immunodeficiency, HIV infection etc
  • Active pulmonary tuberculosis;
  • Has an obvious factor influencing oral drug absorption, such as unable to swallow, chronic diarrhea and intestinal obstruction, etc
  • Patients who received major surgical operations or experienced severe traumatic injuries, bone fracture, or ulcers within 4 weeks before screening.
  • Severe weight loss (> 10%) Within 6 weeks before Random
  • Patients who had obvious hemoptysis (>50ml/day) within 3 months before screening; Patients who experienced bleeding symptoms of clinical significance within 3 months before screening, or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc;
  • Patients who manifested arterial/venous thrombus events, e.g. cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening.
  • Allergic reactions to anotol or excipients in experimental drugs.
  • Allergic reactions to contrast medium
  • Patients have participated in other antitumor drug clinical trials Within 4 weeks before enrollment or prepare to receive systemic anti-tumor treatment during the study or Within 4 weeks before randomization
  • Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.

Trial locations and contacts

6 sites in 1 country.

juan li contact

+86 13880276636

dr.lijuan@hotmail.com

6 sites in 1 country

China6 sites, 6 recruiting

  • Sichuan Cancer Hospital

    Chengdu, Sichuan, 610041

    juan li, doctor, +8613880276636, dr.lijuan@gmail.com

    rui shi, doctor, +8613880898008, shirui729@hotmail.com

    Recruiting

  • Chengdu fifth people's hospital

    Chengdu

    mei mei

    mei mei

    Not yet recruiting

  • People's hospital of deyang city

    Deyang

    zhaohong chen

    zhaohong chen

    Not yet recruiting

  • The affiliated hospital of southwest medical university

    Luzhou

    Sheng Lin

    Sheng Lin

    Not yet recruiting

  • Nanchong central hospital

    Nanchong

    xin hu

    xin hu

    Not yet recruiting

  • Suining central hospital

    Suining

    qiang zhou

    qiang zhou

    Not yet recruiting

Other trials in China

About this study

Official title: Efficacy and Safety of Anlotinib Combined With Platinum Plus Pemetrexed in T790M Mutation Negative Metastastic Non-squamous Non-small-cell Lung Cancer After Progression on First-line EGFR TKI: a Phase II, Muti-center, Single Arm Study

This study is conducted to explore the safety and efficacy of anlotinib, a tyrosine kinase inhibitors of vascular endothelial growth factor receptor 2（VEGFR）、FGFR（fibroblast growth factor receptor）, platelet-derived growth factor receptor（PDGFR） and tumor cell proliferation related kinase c-Kit, combined with platinum plus pemetrexed in T790M mutation negative metastatic non-squamous non-small cell lung cancer(NSCLC) after the failure of EGFR-TKI.

Read the detailed description

Anlotinib, an oral highly potent tyrosine-kinase inhibitor targeting VEGFR、PDGFR、FGFR and c-kit，has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer(NSCLC).

In the phase Ⅲ study ALTER0303, patients who failed at least two kinds of systemic chemotherapy (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 5.37 months and 9.63 months, the placebo group PFS and OS were 1.4 months and 6.3 months. Therefore,we envisage using anlotinib plus platinum plus pemetrexed treat the EGFR wild-type metastatic non-small cell lung cancer patients who were failure in the treatment of chemotherapy with platinum containing drugs, to further improve the patient's PFS.

The study is divided into two stages，phase I use a dose escalation trial design to explore the safety, tolerability, dose-limiting toxicities(DLT), Maximum Tolerable Dose(MTD), A cohort of 3~6 subjects will be enrolled at each dose level, If 0 of 3 or ≤ 1 of 6 subjects experience a DLT, the phase I trial will move ahead to the next dose until ≥ 2 of 6 subjects experience a DLT，and the current dose will be considered the MTD. Following completion of the dose escalation trial and determination of MTD（Phase I）, a single arm study including 44 subjects may be enrolled to further evaluate safety, tolerability, and efficacy of anlotinib in combination with platinum plus pemetrexed in the same target population（phase II）. Phase II is to designed to explore the anti-tumor activity of anlotinib combined with platinum plus pemetrexed in T790M mutation negative metastatic non-squamous non-small cell lung cancer(NSCLC) after the failure of EGFR-TKI.

Being tested
anlotinib 8mg + AP/PC, anlotinib 10mg + AP/PC, anlotinib 12mg + AP/PC, anlotinib + AP/PC
Keywords
non small cell lung cancer, anlotinib, pemetrexed, T790M negative
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 8mg + AP/PCDrug

    Also called Pemetrexed/Cisplatin or Pemetrexed/Carboplatin

    anlotinib 8mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.

  • anlotinib 10mg + AP/PCDrug

    Also called Pemetrexed/Cisplatin or Pemetrexed/Carboplatin

    anlotinib 10mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.

  • anlotinib 12mg + AP/PCDrug

    Also called Pemetrexed/Cisplatin or Pemetrexed/Carboplatin

    anlotinib 12mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.

  • anlotinib + AP/PCDrug

    anlotinib doses to be determined following the completion of Phase I of the study, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.

Study groups in NCT03706287
Study groupRoleWhat they receive
Anlotinib + AP/PCExperimentalNot described
Receives: Drug: anlotinib 8mg + AP/PC; Drug: anlotinib 10mg + AP/PC; Drug: anlotinib 12mg + AP/PC; Drug: anlotinib + AP/PC

What is being measured

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

  1. Progression-free survival (PFS)

    PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.

    Measured: Up to 24 months

  2. Dose limiting toxicity (DLT)

    Dose Limiting Toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria

    Measured: Estimated about 6 months

  3. Maximum tolerance dose (MTD)

    Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT reported.

    Measured: Estimated about 6 months

Secondary outcomes (4)

  1. Objective response rate(ORR)

    To determine ORR of Anlotinib Anlotinib combined with Platinum-based Pemetrexed in T790M mutation negative Advanced NSCLC. ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.

    Measured: Up to 24months

  2. Disease Control Rate (DCR)

    Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.

    Measured: Up to 24months

  3. Duration of Response (DOR)

    Defined as the the time from first confirmed CR or PR until the first date of either objective disease progression or death due to any cause.

    Measured: Up to 24months

  4. Safety (Number of Participants with Adverse Events as a Measure of Safety and Tolerability)

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

    Measured: Until 21 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 posted15 Oct 2018
  2. Study start6 Dec 2018
  3. Primary completion10 Mar 2021 (estimated)
  4. Study completion10 Mar 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03706287
Sponsor's protocol ID
ALTER-L022
Status last verified
Apr 2020
First submitted
7 Oct 2018
Last updated
6 Apr 2020
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing anlotinib 8mg + AP/PC, anlotinib 10mg + AP/PC and anlotinib 12mg + AP/PC in people with Lung Cancer Metastatic, run by Sichuan Cancer Hospital and Research Institute at 6 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 11 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 6 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 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?

Results are not available in the source record.

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

Contact juan li (+86 13880276636, dr.lijuan@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: Up to 24 months). The study lists 3 primary outcomes in all. 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 NCT03706287.

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 6 Apr 2020.

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