Overview

Anlotinib Combined With Pemetrexed And Carboplatin as First-line Treatment in Advanced Nonsquamous NSCLC

Status:
Recruiting
Trial end date:
2021-08-31
Target enrollment:
0
Participant gender:
All
Summary
In recent years, with the progress in the treatment field, Non-Small Cell Lung Cancer(NSCLC) has become the most successful cancer species in precision medicine. Patients with positive driving genes such as EGFR, ALK, ROS1, BRAF and so on have clearly targeted drugs, which bring survival benefits to patients.However, about 50% of patients still lack a clear driving gene target, which has become the focus of current research.In the field of wild-type NSCLC with negative driver genes, the classic first-line treatment regimen is the two-drug regimen containing platinum.The study by Kimura T in the first-line treatment of 54 wild-type advanced NSCLC patients with carboplatin and pemetrexed showed that the ORR, mPFS and mOS of patients with wild-type non-squamous NSCLC treated with carboplatin permetrexine were 35.8%, 5.4 months and 12.7 months respectively. Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development.In the phase Ⅲ study, 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 9.46 months, the placebo group PFS and OS were 1.4 months and 6.37 months. The efficacy and safety of Anlotinib combined with Pemetrexed and Carboplatin followed by maintenance therapy with Anlotinib plus Pemetrexed as the first-line treatment in patients with advanced nonsquamous NSCLC deserve further exploration.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Henan Cancer Hospital
Collaborator:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Treatments:
Carboplatin
Pemetrexed
Criteria
Inclusion Criteria:

- Signed the informed consent form prior to patient entry;

- Male or female patients aged 18-75 years old;

- Diagnosed with advanced NSCLC (phase IIIB/IV) through pathology, Neoadjuvant
chemotherapy, or postoperative adjuvant chemotherapy or neoadjuvant chemotherapy
combined with postoperative adjuvant chemotherapy or targeted chemoradiotherapy for
local advanced disease recurrence within 6 months after completion;

- In the past 3 months at least one target lesion that had not previously been
irradiated,and at least one direction with the longest diameter at baseline greater
than 10 mm (shorter diameter required not less than 15 mm if lymph nodes are
involved)could be imaged by CT scan or MRI;

- Expected Survival Time: Over 6 months;

- Had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1
(on a 5-point scale, with higher scores indicating increasing disability);

- 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, no correction by G-CSF and other hematopoietic stimuli): HB≥90 g/L; ANC ≥
1.5×10^9/L; PLT ≥80×10^9/L;(2)Biochemical examinations must meet the following
criteria: TBIL<1.5×ULN; ALT and AST < 2.5×ULN, and for patients with liver metastases
< 5×ULN; Serum Cr ≤ 1.25×ULN or endogenous creatinine clearance > 60 ml/min
(Cockcroft-Gault formula);

- Women of child-bearing age should take appropriate contraceptive measures and should
not breastfeed from screening to 3 months after stopping the study and
treatment.Before starting administration, the pregnancy test was negative, or one of
the following criteria was met to prove that there was no risk of pregnancy:

1. Postmenopause is defined as amenorrhea at least 12 months after age 50 and
cessation of all exogenous hormone replacement therapy;

2. Postmenopausal women under the age of 50 May also be considered postmenopausal if
their amenorrhea is 12 months or more after the cessation of all exogenous
hormone therapy and their luteinizing hormone (LH) and follicle-stimulating
hormone (FSH) levels are within the reference value range of laboratory
postmenopausal;

3. Has undergone irreversible sterilization surgery, including hysterectomy,
bilateral ovectomy or bilateral salpingectomy, except for bilateral tubal
ligation.

For men, consent is required to use appropriate methods of contraception or to be
surgically sterilized during the trial and 8 weeks after the last administration of the
trial drug.

Exclusion Criteria:

- Small cell lung cancer (including lung cancer mixed with small cell lung cancer and
non-small cell lung cancer),Lung sarcomatoid carcinoma;

- Had histologically confirmed lung squamous cell carcinoma, or adenosquamous carcinoma;

- Patients with pathological fracture in bone metastasis of non-small-cell lung cancer;

- Tumor histology or cytology confirmed EGFR mutagenesis [EGFR sensitive mutations
include 18 exon point mutations (G719X), 19 exon deletions, 20 exon S768I mutations
and 21 exon point mutations (L858R and L861Q)] and ALK gene rearrangement positivity,
include EGFR/ALK status cannot be determined for various reasons;

- 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. Active 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 and metastases in
midbrain, pons, cerebellum, medulla oblongata, or spinal cord, brain metastases
and local radiotherapy after two weeks to allow group);

2. The patient is participating in other clinical studies or completing the previous
clinical study in less than 4 weeks;

3. Had malignant tumors except NSCLC within 5 years before enrollment(except for
patients with cervical carcinoma in situ , basal cell or squamous cell skin
cancer who have undergone a curative treatment, local prostate cancer after
radical resection, ductal carcinoma in situ or papillary thyroid cancer after
radical resection);

4. 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;

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

6. 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;

7. Severe acute or chronic infections requiring systemic treatment;

8. 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%;

9. There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for
trauma;

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

11. Long-term unhealed wounds or fractures;

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

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

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

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

- Physical examination and laboratory 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 more than 1 x
103 copy /ml; Hepatitis c: HCV RNA is positive and liver function is abnormal);
Combined with hepatitis b and hepatitis c infection;

3. Serious diseases that endanger patients' safety or affect patients' completion of
research,according to the researchers' judgment.