Concurrent Chemoradiotherapy Combination With Anlotinib for Unresectable Stage III NSCLC Patients

NCT03672136 | Unknown Phase 2 DMC

• 1 other identifier: ALTER0300
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether concurrent chemoradiotherapy combination with Anlotinib is safe, effective in the treatment of unresectable stage III NSCLC patients.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression Free Survival

  2 years

Secondary Outcomes (3)

• OS

  2 years

• ORR

  2 years

• DCR

  2 years

Study Arms (1)

Concurrent Chemoradiotherapy+Anlotinib

EXPERIMENTAL

1. Radiotherapy: Thoracic radiotherapy dose will be 2.0Gy per day, given 5 days a week, to cumulative dose of 60～66Gy. If radiotherapy and chemotherapy are conducted in the same day, chemotherapy should be priority to radiotherapy. 2. Chemotherapy: Platinum based dual drug regime determined by researcher.After finishing concurrent chemoradiotherapy, there is no need of maintenance chemotherapy. 3. Anlotinib: Combined with 12mg/d QD Anlotinib on the first, second weeks and fourth, fifth weeks of radiotherapy, that is on the day1\~14, day22\~36. 4. Maintenance therapy: One month after finishing concurrent chemoradiotherapy, 12mg/d QD Anlotinib can be administrated, each cycle is defined as 2 weeks on-treatment followed by 1 week off-treatment. The treatment can continue until disease progression or treatment intolerance, but should not exceed 24 months. 5. During the course of study, it's not allowed to receive other anti-tumor therapy.

Drug: Anlotinib; Other: Concurrent Chemoradiotherapy

Interventions

Anlotinib DRUG

Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD α/β, c-Kit and Ret.

Concurrent Chemoradiotherapy+Anlotinib

Concurrent Chemoradiotherapy OTHER

Concurrent chemoradiotherapy as the current standard of care for unresectable stage III non small cell lung cancer patients

Concurrent Chemoradiotherapy+Anlotinib

Eligibility Criteria

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

You may qualify if:

• Patients voluntarily participate in this study, signed informed consent.
• Patients pathologically diagnosed as locally advanced (IIIB / IV) unresectable non-small cell lung cancer, with measurable lesions; IIIa3 patient: Multiple stations lymph node metastasis detected by mediastinoscope, other lymph node biopsy or PET-CT; IIIa4 patient: Bulky or stable multiple stations N2 lymph node metastasis (Bulky lymph node: short diameter \> 2cm in spiral CT imaging, especially the extranodal invasion); and IIIb patient; T3/4 patient with several ipsilateral or contralateral satellite nodules metastasis will be excluded.
• Detection of genotypes by providing detectable specimens (tissue) prior to enrollment: patients with negative EGFR mutation, or ALK rearrangement test results.
• Patients aged between 18 -75 years; with ECOG PS Scoring: 0\~1 point; with expected survival time\>3 months.
• Patients with normal organ function within 7 days prior to treatment, the following criteria are met:
• a) blood routine examination criteria (without blood transfusion in 14 days) : i) hemoglobin (HB) ≥100g/L; ii) white blood cell (WBC)≥ 3.0×10e9/L, absolute neutrophil count (ANC) ≥1.5×10e9/L; iii) platelet (PLT) ≥100×10e9/L; b) biochemical tests meet the following criteria: i) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN, if liver metastasis occurred, ALT and AST ≤5 ULN; iii) serum creatinine (Cr) ≤1.5 ULN or creatinine clearance (CCr) ≥60mL/min;
• Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥50% lower limit of normal (LLN);
• Lung function evaluation: forced expiratory volume in first second (FEVI)≥1.45L/s.

You may not qualify if:

• Patients who had previously used anlotinib hydrochloride capsules;
• Patients with small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer);
• Patients with empty lung squamous cell carcinoma, or non-small cell lung cancer with hemoptysis (\>20 mL/day);
• Patients had other malignancies in the past 5 years or currently, except undergone resection and at least 5 years of progression free survival or cured cervical cancer in situ, basal cell carcinoma and superficial bladder tumor;
• Patients who planned to receive systemic anti-tumor therapy within 4 weeks prior to allocation or during the course of this study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy, except the immunoregulation agents, such as thymosin and lentinan;
• Patients with more than common terminology criteria for adverse events (CTC AE) level 1 unmitigated toxicity due to any previous treatment, not including hair loss;
• Patients have a variety of factors that affect oral medication (such as cannot swallow, chronic diarrhea and intestinal obstruction, etc.);
• Patients with pleural effusion or ascites, causing respiratory syndrome (≥ CTC AE level 2 dyspnea);
• Patients with any severe and/or uncontrolled disease, including:
• blood pressure control is not ideal (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg);
• myocardial ischemic or myocardial infarction, arrhythmia (including QTc ≥480 ms) and ≥ 2 levels of congestive heart failure (NYHA classification);
• active or uncontrollable serious infection (≥CTC AE Level 2 infection);
• liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis need to be treated with antiretroviral therapy;
• renal failure requires hemodialysis or peritoneal dialysis;
• history of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or history of organ transplantation;

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

SHANDONG Cancer Hospital and Institute

Jinan, Shandong, 250000, China

Location

Related Publications (3)

• Pritchard RS, Anthony SP. Chemotherapy plus radiotherapy compared with radiotherapy alone in the treatment of locally advanced, unresectable, non-small-cell lung cancer. A meta-analysis. Ann Intern Med. 1996 Nov 1;125(9):723-9. doi: 10.7326/0003-4819-125-9-199611010-00003.

  PMID: 8929005 RESULT

• Bao Y, Peng F, Zhou QC, Yu ZH, Li JC, Cheng ZB, Chen L, Hu X, Chen YY, Wang J, Wang Y, Ma HL, Xu ZM, Lu RB, Deng XW, Chen M. Phase II trial of recombinant human endostatin in combination with concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer. Radiother Oncol. 2015 Feb;114(2):161-6. doi: 10.1016/j.radonc.2014.11.039. Epub 2014 Dec 9.

  PMID: 25497558 RESULT

• Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1569-1575. doi: 10.1001/jamaoncol.2018.3039.

  PMID: 30098152 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

anlotinib; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• JINMING YU, doctor

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming Huan Li, doctor

CONTACT

131 5303 5389; sy_lmh2001@163.com

JINMING YU, doctor

CONTACT

13806406293; jn7984729@public.jn.sd.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: September 14, 2018
• Study Start: November 1, 2018
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2020
• Last Updated: September 14, 2018

Record last verified: 2018-09

Locations

CN (1)