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NSCLC Stage IVPhase 1/2NCT04507906

Nivolumab Combined With Anlotinib as Re-challenge Treatment in Advanced NSCLC

A Phase 1/2 study testing Nivolumab Combined with Anlotinib in people with NSCLC Stage IV and Checkpoint Inhibitor, run by Shanghai Chest Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase Ib/IIa, open-label, single center study, aiming to investigate safety and efficacy of nivolumab (administered intravenously) in combination with anlotinib (administered orally) in immunotherapy-treated advanced NSCLC. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
NSCLC Stage IV, Checkpoint Inhibitor
What is being tested?
Nivolumab Combined with Anlotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteChina
Study dates
2 Nov 2020to 31 Mar 2022
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

  • According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage III B/III C), metastatic or recurrent (stage IV) NSCLC confirmed by histology or cytology who are unable to undergo surgery and radical concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.
  • Without active brain metastasis
  • Previously treated with ICIs with progressive disease.
  • Age ≥18 years and ≤75 years;
  • ECOG PS score: 0 to 1
  • Palliative radiotherapy must be completed 7 days before the first dose of study drugs;
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  • The main organs function is normal, that is, the following criteria met:
  • Good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /L, hemoglobin ≥90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment]
  • Biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 times ULN; if the subject is receiving anticoagulant treatment, PT should be within the prescribed range of use of anticoagulant drugs;
  • Women of child-bearing age should agree to take contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study and within 6 months after the study; non-breast-feeding patients whose serum or urinary pregnancy test should be negative; male patients should agree to take contraceptive measures during the study and within 6 months after the study.
  • Patients are voluntarily enrolled into the study, sign the informed consent form and have good compliance.

Who cannot join

  • Patients who meet any of the following criteria will be excluded:
  • Subjects with active CNS metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
  • Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or central squamous cell carcinoma with cavity;
  • With obvious hemorrhage symptom
  • With driver mutation (EGFR/ALK/ROS1) or mutation status are unknown
  • Patients who have not received IO as frontline treatment;
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  • Patients who have grade 3 AEs when treated with IO
  • Patients with many factors affecting oral medication, such as dysphagia, gastrointestinal resection, chronic diarrhea and intestinal obstruction;
  • Patients who are known to have active brain metastases, spinal cord compression, carcinomatous meningitis, or brain or leptomeningeal disease diagnosed by CT or MRI at the time of screening;
  • Patients with severe and / or uncontrolled diseases, such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months before randomization, severe uncontrolled arrhythmias; uncontrolled blood pressure (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);
  • Active or uncontrolled serious infection;
  • Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
  • Not completely controlled eye inflammation or eye infection, or any condition that may lead to the above-mentioned ocular diseases
  • Poorly controlled diabetes (fasting blood glucose (FBG) > 10mmol/L);
  • Routine urine test result indicates that urine protein ≥++, and 24-hour urine protein quantitation is confirmed to be > 1.0 g;
  • Active tuberculosis;
  • Uncontrolled hypercalcemia (> 1.5 mmol/L calcium ion or calcium > 12 mg/dL or corrected serum calcium > ULN), or symptomatic hypercalcemia requiring continued diphosphate therapy;
  • Long-term unhealed wounds or fractures;
  • Patients who have a history of psychotropic drug abuse and cannot abstain from it or have mental disorders;
  • Patients who are known to have severe allergies (≥ grade 3) to active ingredients and any excipients of dacomitinib
  • Patients who have other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) at the same time; patients who are evaluated by the investigator to have concomitant diseases that seriously endanger the safety of the patients or affect the patients completing the study.
  • The subjects or their sexual partners cannot or refuse to take effective contraceptive measures during the clinical trial
  • Pregnant or breast-feeding women
  • Previously treated including treated with traditional Chinese medicine
  • Patients who are allergic to any of the agent or any ingredient
  • Patients in other situations who are evaluated by the investigator to be ineligible to be enrolled

Trial locations and contacts

1 site in 1 country.

China1 site

  • Shanghai Chest hospital

    Shanghai, Shanghai Municipality, 200030

Other trials in China

About this study

Official title: Safety and Efficacy of Nivolumab Combined With Anlotinib in Advanced Non-small Cell Lung Cancer Patients Previously Treated With Checkpoint Inhibitor-A Single Center and Exploratory Study

This is a phase Ib/IIa, open-label, single center study, aiming to investigate safety and efficacy of nivolumab (administered intravenously) in combination with anlotinib (administered orally) in immunotherapy-treated advanced NSCLC. The study has been designed to allow an investigation of the optimal combination dose and schedule while ensuring the safety of patients with intensive safety monitoring. There are two main parts to this study; Part A, combination dose finding and Parts B, dose expansion. Part B will either be initiated if RP2D reached in Part A, or not initiated if RP2D was not reached in Part A.

Part A has been designed to identify the recommended dose of combination of nivolumab plus anlotinib for further clinical evaluation based upon assessment of the safety and tolerability data collected during the first 21 days (cycle 1, 21 days per cycle). The 21-day assessment period was selected as the major toxicities leading to cessation of dose de-escalation in such Phase I oncology studies (haematological, gastrointestinal, liver enzymes) are anticipated to present within this duration. "3+3"design was used in the dose finding cohort.

If RP2D was reached in Part A, eligible patients would be enrolled and receive nivolumab (360mg q3w, intravenously) plus anlotinib (RP2D, QD from day 1 to 14 of a 21-day cycle) till disease progression (PD) withdraw of consent, or unacceptable toxicity to further evaluate the safety, tolerability and efficacy in terms of ORR , DCR, DOR, PFS and OS. The tumor response will be evaluated according to RECIST Version 1.1 every 6 weeks.

Being tested
Nivolumab Combined with Anlotinib
Keywords
NSCLC, Nivolumab, Anlotinib
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.

  • Nivolumab Combined with AnlotinibDrug

    In combination dose finding phase, Phase 1b will begin with Dose Level 1; anlotinib 12 mg/day orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360mg q3w, intravenously) will be administered to eligible subjects on a 21-day treatment cycle. Two dose de-escalation steps are included: Dose Level 2 (anlotinib 10 mg/day orally, from days 1 to 14 in a 21-day cycle) and nivolumab 360mg q3w, intravenously) and Dose Level 3 (anlotinib 8 mg/day orally, from days 1 to 14 in a 21-day cycle) and nivolumab 360mg q3w, intravenously).If RP2D was reached in Part A, eligible patients would be enrolled and receive nivolumab (360mg q3w, intravenously) plus anlotinib (RP2D, QD from day 1 to 14 of a 21-day cycle) .

Study groups in NCT04507906
Study groupRoleWhat they receive
Nivolumab + Anlotinib ArmOtherNot described
Receives: Drug: Nivolumab Combined with Anlotinib

What is being measured

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

  1. Objective response rate (ORR)

    Patients who were assessed as partial response or complete response

    Measured: 6-9 weeks

Secondary outcomes (3)

  1. Disease control rate (DCR)

    Patients who were assessed as partial response, complete response or stable disease

    Measured: 6-9 weeks

  2. Progression-free survival (PFS)

    Time from enrollment to progression or death

    Measured: 5-7 months

  3. Overall survival (OS)

    Time from enrollment to death of any cause

    Measured: 13-15 months

Timeline

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

  1. First posted11 Aug 2020
  2. Study start2 Nov 2020
  3. Primary completion31 Mar 2022
  4. Study completion31 Mar 2022

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
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04507906
Sponsor's protocol ID
LS2025
Status last verified
Jun 2022
First submitted
8 Aug 2020
Last updated
28 Jun 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Zhang B, Liu H, Shi C, Gao Z, Zhong R, Gu A, Chu T, Wang H, Xiong L, Zhang W, Zhang X, Yan B, Teng J, Wang W, Bai H, Qiao R, Cheng L, Kuang Y, Zhao R, Zhong H, Han B. Safety and efficacy of multi-target TKI combined with nivolumab in check-point inhibitor-refractory patients with advanced NSCLC: a prospective, single-arm, two-stage study. BMC Cancer. 2024 Jun 11;24(1):715. doi: 10.1186/s12885-024-12479-0.

    PubMed 38862908

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab Combined with Anlotinib in people with NSCLC Stage IV and Checkpoint Inhibitor, run by Shanghai Chest Hospital 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 11 inclusion and 26 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: finished, as of the sponsor's last update on 28 Jun 2022. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Objective response rate (ORR) (time frame: 6-9 weeks). 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 NCT04507906, 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 28 Jun 2022.

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