Overview

A Trial of Anlotinib Combined With Docetaxel in EGFR Mutations Advanced Non Small Cell Lung Cancer Patients

Status:
Recruiting
Trial end date:
2022-10-01
Target enrollment:
0
Participant gender:
All
Summary
Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development. It can inhibit angiogenesis-related kinases, such as VEGFR, FGFR, PDGFR and tumor cell proliferation related kinase c-Kit kinase. In the Phase III study, patients who failed at least two systemic chemotherapy (third-line or above) or were intolerant of the drugs were treated with anlotinib or placebo. The PFS and OS in the anlotinib group were 5.37 months and 9.63 months, respectively. The placebo group PFS and OS were 1.4 months and 6.3 months. Therefore, it is envisaged to use anlotinib combined with docetaxel to treat EGFR mutations advanced non small cell lung cancer to further improve the patient's PFS or OS.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Shandong Cancer Hospital and Institute
Collaborator:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Treatments:
Docetaxel
Criteria
Inclusion Criteria:

- The subjects voluntarily join the study and sign an informed consent form, with good
compliance and cooperation with follow-up.

- EGFR mutation-positive、ALK mutation-negative;Patients have progressed after receiving
EGFR targeted and chemotherapy as first-line treatment.

- Patients who were resistant to EGFR targeted treatment need to receive T790M mutation
test. If the test is positive and Patients have not orally taken osimertinib or
almonertinib, patients need to orally taken osimertinib or almonertinib and be
progressed prior to enrollment.

- ≥ 18 and ≤ 75 years of age; female or male.

- Diagnosed with local advanced and/or metastatic NSCLC (phase IIIB、IIIC or IV) through
Histology or cytology (using the new version of staging announced by the American
Joint Committee on Cancer on January 1, 2018), or recurrent non- squamous non-small
cell lung cancer. Noted: failed from prior treatment means(1) progress disease
confirmed by definite imageology and clinical evidence during treatment or after the
last treatment; (2) Patients withdrew from treatment because of intolerant adverse
events, the intolerant adverse events refer to≥ level IV hematologic toxicities or ≥
level III non-hematologic toxicities or ≥ level 2 damages of major organs such as
heart/liver/kidney in CTC AE 4.0.

- There is at least one target lesion that has not received radiotherapy, and it can be
accurately measured by magnetic resonance imaging (MRI) or computed tomography (CT) in
at least one direction (the maximum diameter needs to be recorded), where the maximum
tumor diameter is >10 mm; the shortest diameter of the lymph node is >15mm.

- Expected survival time: at least 3 months

- ECOG PS:0-1

- The damage caused by other treatments has been recovered (NCI-CTCAE 4.0 version
classification≤level 1); Radiotherapy (except local palliative radiotherapy)≥ 2 weeks.

- The main organs function are normally, the following criteria are met

1. Blood routine examination criteria should be met (no blood transfusion and blood
products within 14 days): HB≥90 g/L; ANC ≥ 1.5×10^9/L; PLT ≥80×10^9/L;

2. Biochemical examinations must meet the following criteria: TBIL<1.5ULN; ALT and
AST < 2.5ULN, and for patients with liver metastases < 5ULN; Serum Cr ≤ 1.25ULN
or endogenous creatinine clearance > 45ml/min (Cockcroft-Gault formula);

- Women of childbearing potential must have taken reliable contraceptive measures or the
result of serum or urine pregnancy test should be negative within 7 days prior to
study enrollment, and willing to use and utilize an adequate method of contraception
throughout treatment and for at least 8 weeks after the last test drug administration.
Man participants should agree to use and utilize an adequate method of contraception
throughout treatment and for at least 8 weeks after the last test drug administration
or surgical sterilization.

Exclusion Criteria:

- Squamous carcinoma of lung (including Adenosquamous carcinoma); Small cell lung cancer
(including lung cancer mixed with small cell lung cancer and non- small cell lung
cancer);

- Have used Anlotinib Hydrochloride、docetaxel before; Postoperative adjuvant therapy
with docetaxel is acceptable.

- Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood
vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood
vessel; or there is a significant pulmonary cavity or necrotizing tumor;

- Medical history and combined history:

1. Significant brain metastases, cancerous meningitis, spinal cord compression, or
imaging CT or MRI screening for brain or pia mater disease (a patient with brain
metastases who have completed treatment and stable symptoms in 28 days before
enrollment may be enrolled, but should be confirmed by brain MRI, CT or
venography evaluation as no cerebral hemorrhage symptoms);

2. The patient is participating in other clinical studies.

3. Other active malignancies that require simultaneous treatment;

4. Patients with 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 a possible curative
treatment and have no disease recurrence within 5 years from the start of
treatment;

5. Patients with previously systemic anti-tumor treatment-related adverse reactions
(excluding hair loss) who have not recovered to NCI-CTCAE ≤level 1;

6. Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds
or APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or
anticoagulant therapy; Note: Under the premise of prothrombin time international
normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million
to 12,000 U) or low-dose aspirin (daily dosage ≤ 100 mg) is allowed for
preventive purposes;

7. Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed
24-hour urine protein ≥ 1.0g;

8. The effects of surgery or trauma have been eliminated for less than 14 days
before enrollment in subjects who have undergone major surgery or have severe
trauma;

9. Severe acute or chronic infections requiring systemic treatment;

10. Suffering from severe cardiovascular disease: myocardial ischemia or myocardial
infarction above grade II, poorly controlled arrhythmias (including men with QTc
interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV
Insufficient function, or cardiac color Doppler ultrasound examination indicates
left ventricular ejection fraction (LVEF) <50%;

11. Peripheral neuropathy with ≥CTCAE degree 2 currently exists, except for trauma
caused;

12. Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including
pleural effusion, ascites, pericardial effusion) requiring treatment;

13. Long-term unhealed wounds or fractures;

14. Decompensated diabetes or other ailments treated with high doses of
glucocorticoids;

15. Factors that have a significant impact on oral drug absorption, such as inability
to swallow, chronic diarrhea, and intestinal obstruction;

16. Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3
months before enrollment; or significant clinically bleeding symptoms or defined
bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer,
baseline fecal occult blood ++ and above, or suffering from vasculitis;

17. Events of arterious/venous thrombosis occurring within 12 months prior to
enrollment, such as cerebrovascular accidents (including transient ischemic
attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and
pulmonary embolism;

18. Planned for systemic anti-tumor therapy, including cytotoxic therapy, signal
transduction inhibitors, immunotherapy. Extended-field radiotherapy (EF-RT) was
performed within 3 weeks before grouping or limited-field radiotherapy to be
evaluated for tumor lesions within 2 weeks before grouping;

19. Uncontrollable hypertension with two or more combined treatments (systolic blood
pressure ≥145 mmHg or diastolic blood pressure ≥90 mmHg);

20. Have a history of psychotropic substance abuse and are unable to quit or have a
mental disorder;

- Physical examination and laboratory examination findings

1. A known history of HIV testing positive or acquired immunodeficiency syndrome
(AIDS);

2. untreated active hepatitis (hepatitis b: HBsAg positive and HBV DNA ≥500 IU/ml;
Hepatitis c: HCV RNA is positive and liver function is abnormal); Combined with
hepatitis b and hepatitis c infection;

- Other factors that may cause the study to be terminated midway according to the
researchers' judgment, such as other serious diseases or severe laboratory test
abnormalities or factors that will endanger patients' safety, or family or society
factors of test data and sample collection.