Study of Anlotinib Combined With Pemetrexed in Patients With Advanced Nonsquamous NSCLC

NCT03778138 | Unknown Phase 2

• 1 other identifier: ALTER-L025
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

In recent years, with the progress in the treatment field, 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.he phase II clinical study of pemetrexed in the second-line treatment of advanced non-small cell lung cancer patients with pemetrexed versus carboplatin pemetrexed showed that the median PFS time in the pemetrexed group was 3.5 months. 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 9.63 months, the placebo group PFS and OS were 1.4 months and 6.3 months. The efficacy and safety of anrotinib combined with pemetrexed in the second-line treatment of advanced non-squamous and non-small cell patients deserve further exploration.

Conditions

Non-squamous Cell Non-Small Cell Lung Cancer

Keywords

Advanced nonsquamous Non-Small Cell Lung Cancer; Anlotinib Combined With Pemetrexed

Outcome Measures

Primary Outcomes (1)

• Progress free survival (PFS) based on investigator assessment

  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.

  each 42 days up to PD or death(up to 24 months)

Secondary Outcomes (4)

• Objective Response Rate based on investigator assessment

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• Disease Control Rate（DCR）

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• Overall Survival（OS）

  each 42 days up to intolerance the toxicity or PD (up to 24 months) .

• Safety(Number of Participants with Adverse Events and Clinical laboratory numerical evaluation as a Measure of Safety)

  each 42 days up to intolerance the toxicity or PD (up to 24 months) .

Study Arms (1)

Anlotinib plus Pemetrexed

EXPERIMENTAL

Anlotinib(12mg QD PO d1-14, 21 days per cycle) plus Pemetrexed (500mg/m2 IV d1)

Drug: Anlotinib plus Pemetrexed

Interventions

Anlotinib plus Pemetrexed DRUG

Anlotinib(12mg QD PO d1-14, 21 days per cycle) plus Pemetrexed (500mg/m2 IV d1)

Anlotinib plus Pemetrexed

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Patients with negative driver genes who had previously only received first-line platinum double-drug therapy progression or intolerance;
• 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);
• If there is central nervous system metastases,they must be asymptomatic central nervous system metastases;
• 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:
• Postmenopause is defined as amenorrhea at least 12 months after age 50 and cessation of all exogenous hormone replacement therapy;
• 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;
• 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.

You may not qualify if:

• 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;
• EGFR、ALK mutation-positive by genetic testing technology (pathological examination results of other hospitals are acceptable) and who receive EGFR-TKI and ALK-TKI targeted drug therapy,except 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;
• have used Pemetrexed before and progressed;
• Patients with uncontrolled pleural effusion need to be treated with other chemotherapy drugs;
• Significant weight loss (more than 10% weight loss in the previous 6 weeks);
• Medical history and combined history：
• Had clinically symptomatic central nervous system metastasis(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 or metastases in midbrain, pons, cerebellum, medulla oblongata, or spinal cord);
• The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks;
• 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);
• Patients with previous anti-tumor treatment-related adverse reactions (excluding hair loss) who have not recovered to NCI-CTCAE ≤1;
• 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;
• Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g;
• 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;

Sponsors & Collaborators

• Henan Provincial People's Hospital: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Henan Provincial People's Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

MeSH Terms

Interventions

anlotinib; Pemetrexed

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Cang Shundong, doctor

  Henan Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cang Shundong, doctor

CONTACT

0086-13592675836; cangshundong@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Anlotinib and Pemetrexed

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 19, 2018
• Study Start: January 1, 2019
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2020
• Last Updated: December 19, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)