Study of Anlotinib Plus Chemotherapy as the First-line Treatment in Patients With Advanced NSCLC

• ClinicalTrials.gov Identifier: NCT03636685
• Recruitment Status: Unknown
• First Posted: August 17, 2018
• Last Update Posted: August 17, 2018
• Sponsor: Chinese Academy of Medical Sciences
• Information provided by (Responsible Party): Shi Yuankai, Chinese Academy of Medical Sciences

Tracking Information

• First Submitted Date: August 13, 2018
• First Posted Date: August 17, 2018
• Last Update Posted Date: August 17, 2018
• Estimated Study Start Date: August 15, 2018
• Estimated Primary Completion Date: August 14, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 16, 2018)

Progress free survival (PFS) [ Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause,whichever came first.up to 12 months ]

progression free survival

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 16, 2018)

• Objective Response Rate (ORR) [ Time Frame: each 21 days up to the toxicity or PD (up to 24 months) ]
  Objective Response Rate
• Disease Control Rate (DCR) [ Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months) ]
  Disease Control Rate
• Overall Survival (OS) [ Time Frame: From enrollment until death (up to 36 months) ]
  Overall survival
• Number of Participants with Adverse Events as a Measure of Safety and Tolerability (Safety) [ Time Frame: Time Frame: each 21 days up to the toxicity or PD (up to 36 months) ]
  Number of Participants with Adverse Events as a Measure of Safety and Tolerability

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Anlotinib Plus Chemotherapy as the First-line Treatment in Patients With Advanced NSCLC
• Official Title: A Phase I/II Study of Anlotinib Combined With Platinum-based Chemotherapy as the First-line Treatment of Patients With Locally Advanced or Advanced Non-Small Cell Lung Cancer
• Brief Summary: Non-small cell lung cancer has the highest morbidity and mortality in China，and platinum-based chemotherapy is the standard first-line treatment for the wild-type NSCLC,however the overall survival still less than one year.Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR2、VEGFR3、PDGFRβ and c-Kit, which has strong effect of anti-angiogenesis.This study is aim to evaluate the efficacy and safety of the combination regimen of anlotinib plus platinum-based chemotherapy as first-line treatment for NSCLC.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Factorial Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• NSCLC
• Adenocarcinoma
• Squamous Cell Carcinoma

Intervention

• Drug: Anlotinib combined with pemetrexed and carboplatin, phase I

  Non-squamous cell lung cancer, Anlotinib Plus PC

  This study will include a sequential evaluation of 3 subjects per dose group. low-dose groups: Anlotinib 8mg per day plus pemetrexed and carboplatin. middle-dose groups: Anlotinib 10mg per day plus pemetrexed and carboplatin. high-dose groups: Anlotinib 12mg per day plus pemetrexed and carboplatin to determine the appropriate dose of anlotinib in combination with paclitaxel and carboplatin

  Other Name: APC I
• Drug: Anlotinib combined with paclitaxel and carboplatin, phase I

  Squamous cell lung cancer, Anlotinib plus TC

  This study will include a sequential evaluation of 3 subjects per dose group. low-dose groups: Anlotinib 8mg per day plus paclitaxel and carboplatin. middle-dose groups: Anlotinib 10mg per day plus paclitaxel and carboplatin. high-dose groups: Anlotinib 12mg per day plus paclitaxel and carboplatin to determine the appropriate dose of anlotinib in combination with paclitaxel and carboplatin

  Other Name: ATC I
• Drug: Anlotinib combined with pemetrexed and carboplatin, phase II
  Anlotinib: established dose QD PO d1-14, pemetrexed,carboplatin, 21 days per cycle after 4-6 cycles, Anlotinib p.o, qd and it should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent
  Other Name: APCII
• Drug: Anlotinib combined with paclitaxel and carboplatin, phase II

  Anlotinib :established dose QD PO d1-14, paclitaxel,carboplatin, 21 days per cycle

  after 4-6 cycles, Anlotinib p.o, qd and it should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent

  Other Name: ATCII

Study Arms

• Experimental: Non-squamous cell lung cancer

  Anlotinib combined with pemetrexed and carboplatin, phase I

  Anlotinib combined with pemetrexed and carboplatin, phase II

  Interventions:

  • Drug: Anlotinib combined with pemetrexed and carboplatin, phase I
  • Drug: Anlotinib combined with pemetrexed and carboplatin, phase II
• Experimental: Squamous cell lung cancer

  Anlotinib combined with paclitaxel and carboplatin, phase I

  Anlotinib combined with paclitaxel and carboplatin, phase II

  Interventions:

  • Drug: Anlotinib combined with paclitaxel and carboplatin, phase I
  • Drug: Anlotinib combined with paclitaxel and carboplatin, phase II

• Publications *: Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 16, 2018): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 14, 2020
• Estimated Primary Completion Date: August 14, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age：18~70 years;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2
• Subjects with histologically or cytologically confirmed locally advanced or advanced NSCLC
• EGFR\ALK\ROS1 wildtype or unknown,or patients with EGFR\ALK\ROS1 mutations but refuse to receive corresponding inhibitors' treatment
• No indications for radiation therapy
• Previously chemotherapy naive or postoperative adjuvant chemotherapy ended more than 1 year
• Subjects with at least one measurable lesion as defined by RECIST (version 1.1),which is confirmed by computed tomography (CT) scan or MRI

Exclusion Criteria:

• Small Cell Lung Cancer
• central lung squamous carcinoma along with cavum, or non-small cell lung cancer along with hemoptysis (>50ml/day)
• Within 30 days before enrollment, the patient had used any chemotherapy drugs in the previous treatment regimen or clinical study; Or, within 14 days before the first administration of the study therapy, the patient has used any targeted anticancer drugs in the previous treatment regimen or clinical study; Or stop other experimental drugs or cancer drugs for less than five half-life of the drug
• Previous use of anti-angiogenic drugs (such as anlotinib, apatinib, bevacizumab, endostar, etc.)
• have got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (4.0), alopecia NOT included
• Spinal cord compression or symptomatic and untreated brain metastases (asymptomatic, stable, no need for steroid treatment for 4 weeks before study start)
• with kinds of factors which affect oral medicine (e.g. failing to swallow, gastrointestinal tract getting resected, chronic diarrhea and ileus)
• Previous histories include: interstitial pneumonia, drug-induced interstitial pneumonia, radiation pneumonia requiring steroid treatment, and clinically proven active interstitial pneumonia
• get arterial/venous thrombosis within 6 months, such as cerebrovascular accidents (including temporary ischemic stoke), prevenous thrombosis, and pulmonary embolism
• Have suffered from hemorrhagic disease or coagulation dysfunction
• diagnosed with disease which will severely endanger the security of patients or influence the completion of this research

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03636685
• Other Study ID Numbers: NCC201807006
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Shi Yuankai, Chinese Academy of Medical Sciences
• Study Sponsor: Chinese Academy of Medical Sciences
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Chinese Academy of Medical Sciences
• Verification Date: August 2018