First-line Combination Treatment Based on Anlotinib

Shanghai Jiao Tong University

Status and phase: Unknown; Phase 1

Conditions: Advanced Stage; Lung Cancer

Treatments: Drug: Anlotinib，Erlotinib，IBI308，Pemetrexed，gemcitabine，carboplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT03628521

ACTION

Details and patient eligibility

About

The aim of this study is to explore safety and therapeutic efficacy of anlotinib combined with erlotinib/chemotherapy/IBI308 as first-line treatment in advanced NSCLC patients. The primary endpoints of the study are safety and objective response rate (ORR);the secondary endpoints are disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients have voluntarily to join the study and give written informed consent for the study
2. Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV Non-Small Cell Lung Cancer (NSCLC)
3. A cytologic diagnosis is acceptable (i.e., FNA or pleural fluid cytology)
4. Mutation status including EGFR, ALK ROS are explicit;
5. At least 1 unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumours (RECIST) criteria.
6. Patients did not receive systemic anti-cancer therapy previously, including traditional Chinese medicine.
7. Able to comply with study and follow-up procedures
8. Age ≥ 18 years and ≤ 75, ECOG PS: 0~1, estimated survival duration more than 3 months;enough organ function;

8)Major organ function

1. For regular test results（no blood transfusion within 14 days）：

   1. Hemoglobin（HB）≥90g/L；
   2. Absolute neutrophils count（ANC）≥1.5×109/L；
   3. Blood platelets（PLT）≥80×109/L

2. Biochemical tests results defined as follows：

   1. Total bilirubin（TBIL）≤1.5 times the upper limit of normal (ULN) ；
   2. Alanine aminotransferase（ALT）and aspartate aminotransgerase AST≤2.5ULN，liver metastases，if any，ALT和AST≤5ULN；
   3. Creatinine（Cr）≤1.5ULN or Creatinine Clearance rate (CCr)≥60 ml/min；

3. Doppler ultrasound assessment：left ventricular ejection fraction (LVEF) ≥the lower limit of normal value(50%).

Exclusion criteria

1. Small cell lung cancer(including patients with mixed small cell lung cancer and non-small cell lung cancer) or central squamous cell carcinoma with cavity
2. Mutation status are unknown
3. Previously (within 5 years) or presently suffering from other malignancies,
4. Symptomatic or uncontrolled brain metastases
5. Unstable systemic disease, including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months or serious cardiac arrhythmia requiring medication
6. History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications
7. Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, or prior surgical procedures affecting absorption
8. Pregnancy or lactation
9. Previously treated including treated with traditional Chinese medicine
10. Patients who are allergic to any of the agent or any ingredient -

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 3 patient groups

arm A

Other group

Description:

Anlotinib combined with erlotinib. Anlotinib will be given at a dose of 10mg once daily on days 1-14 of a 21-day cycle. Erlotinib will be given at a dose of 150mg once daily.

Treatment:

Drug: Anlotinib，Erlotinib，IBI308，Pemetrexed，gemcitabine，carboplatin

arm B

Other group

Description:

Anlotinib combined with chemotherapy. Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle. Pemetrexed (just for adenocarcinoma) will be given intravenously at a dose of 500mg per square meter of body surface area every 3 weeks; gemcitabine (just for squamous carcinoma) will be given intravenously at a dose of 1000mg per square meter of body surface area every 3 weeks; carboplatin will be given intravenously with a target area under the curve of 5 mg per milliliter per minute every 3 weeks.

Treatment:

Drug: Anlotinib，Erlotinib，IBI308，Pemetrexed，gemcitabine，carboplatin

arm C

Other group

Description:

Anlotinib combined with IBI308. Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle. IBI308 will be given intravenously at a dose of 200mg every 3 weeks.

Treatment:

Drug: Anlotinib，Erlotinib，IBI308，Pemetrexed，gemcitabine，carboplatin