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Study of Apatinib as 3rd/4th Line Treatment in Patients With Advanced Non-Squamous Non-small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor (EGFR) (ANSWER)

Primary Purpose

Carcinoma, Non-Small-Cell Lung

Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Apatinib
Placebo
Sponsored by
Jiangsu HengRui Medicine Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring Non-squamous non-small cell lung cancer, Wild-type EGFR, 3rd/4th line treatment, apatinib

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subjects >/= 18 years and </=70 years of age at the time of Informed Consent.
  2. Advanced relapsed or refractory predominantly NSCLC with documented wild-type EGFR.
  3. At least one measurable lesion according to RECIST 1.1.
  4. Failure of second line of chemotherapy.
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  6. Patients must have recovered from any AEs of prior treatments before randamization.
  7. Adequate bone marrow,liver and renal function as assessed by the following laboratory tests conducted within 1 week before randomization. HB ≥ 90g/L; ANC≥1.5×10E+9/L; PLT≥80×10E+9/L; ALT and AST < 2.5×ULN; TBIL ≤1.25×ULN; Cr ≤1.25×ULN;CL>45 ml/min.
  8. Life expectancy of at least three months.
  9. Written informed consent and the willingness and ability to comply with all aspects of the protocol.

Exclusion Criteria:

  1. Presence of types of small-cell, squamous-cell, adeno-squamous-cell lung cancer.
  2. Pregnant or breast-feeding women.
  3. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms).Severe or uncontrolled systemic disease such as clinically significant hypertension(systolic pressure >/= 140 mm Hg and/or diastolic pressure >/= 90 mm Hg), and Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF<50%.
  4. Factors to affect oral administration(inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction).
  5. Coagulation disfunction,hemorrhagic tendency or receiving anticoagulant therapy>/= CTCAE 2 pneumorrhagia or >/= CTCAE 3 hemorrhage in other organs within 4 weeks.
  6. Bone fracture or wounds that was not cured.
  7. Arterial thrombus or phlebothrombosis within 12 months and taking anticoagulant agents.
  8. Mental diseases and psychotropic substances abuse.
  9. Previous treatment with an trial agent within 4 weeks
  10. Previous treatment with VEGFR,platelet derived growth factor receptor(PDGFR) TKIs.
  11. Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
  12. Other coexisting malignant disease (except basal-cell carcinoma and carcinoma in situ of uterine cervix).

Sites / Locations

  • Department of Medical Oncology, Cancer Center, Sun Yet-sen UniversityRecruiting
  • Shanghai Pulmonary HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Apatinib

Placebo

Arm Description

Apatinib tablet administered orally, 750 mg,once daily until progression

Placebo tablet administered orally, once a day until progression

Outcomes

Primary Outcome Measures

Overall Survival（OS)
Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause.The date the patient was recorded alive of last follow-up.Median time results from unstratified Kaplan-Meier estimates.

Secondary Outcome Measures

Progression free survival (PFS)
PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
Objective response rate (ORR)
ORR was defined as the proportion of patients whose best response was Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)] or Partial Response [PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD] over the whole duration of study.
Duration of response (DoR)
DoR was defined as the time from documentation of tumor response to disease progression.
Disease control rate (DCR)
DCR was defined as the proportion of patients whose best response was CR or PR or Stable Disease (SD)
Mean Change From Baseline in European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30)

Full Information

First Posted
January 4, 2015
Last Updated
February 23, 2017
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02332512
Brief Title
Study of Apatinib as 3rd/4th Line Treatment in Patients With Advanced Non-Squamous Non-small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor (EGFR)
Acronym
ANSWER
Official Title
A Randomized, Double-blind, Placebo-controlled, Phase III Trial of Apatinib as 3rd/4th Line Treatment in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor (EGFR)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Unknown status
Study Start Date
January 2015 (undefined)
Primary Completion Date
August 2017 (Anticipated)
Study Completion Date
October 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Apatinib is a new kind of selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2) tyrosine kinase inhibitor (TKI). The investigators have finished the preclinical,phase I and phase II clinical studies and found its promising anti-tumor activity and tolerable toxicities. A disease-control rate of 61.1% and a mPFS of 4.7 months were showed in apatinib phase II study in patients with NSCLC. The study aims to compare the efficacy and safety of apatinib to placebo in advanced non-squamous non-small cell lung cancer patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung
Keywords
Non-squamous non-small cell lung cancer, Wild-type EGFR, 3rd/4th line treatment, apatinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
417 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Apatinib
Arm Type
Experimental
Arm Description
Apatinib tablet administered orally, 750 mg,once daily until progression
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablet administered orally, once a day until progression
Intervention Type
Drug
Intervention Name(s)
Apatinib
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Overall Survival（OS)
Description
Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause.The date the patient was recorded alive of last follow-up.Median time results from unstratified Kaplan-Meier estimates.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Progression free survival (PFS)
Description
PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
Time Frame
24 months
Title
Objective response rate (ORR)
Description
ORR was defined as the proportion of patients whose best response was Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)] or Partial Response [PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD] over the whole duration of study.
Time Frame
24 months
Title
Duration of response (DoR)
Description
DoR was defined as the time from documentation of tumor response to disease progression.
Time Frame
24 months
Title
Disease control rate (DCR)
Description
DCR was defined as the proportion of patients whose best response was CR or PR or Stable Disease (SD)
Time Frame
24 months
Title
Mean Change From Baseline in European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30)
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects >/= 18 years and </=70 years of age at the time of Informed Consent. Advanced relapsed or refractory predominantly NSCLC with documented wild-type EGFR. At least one measurable lesion according to RECIST 1.1. Failure of second line of chemotherapy. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Patients must have recovered from any AEs of prior treatments before randamization. Adequate bone marrow,liver and renal function as assessed by the following laboratory tests conducted within 1 week before randomization. HB ≥ 90g/L; ANC≥1.5×10E+9/L; PLT≥80×10E+9/L; ALT and AST < 2.5×ULN; TBIL ≤1.25×ULN; Cr ≤1.25×ULN;CL>45 ml/min. Life expectancy of at least three months. Written informed consent and the willingness and ability to comply with all aspects of the protocol. Exclusion Criteria: Presence of types of small-cell, squamous-cell, adeno-squamous-cell lung cancer. Pregnant or breast-feeding women. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms).Severe or uncontrolled systemic disease such as clinically significant hypertension(systolic pressure >/= 140 mm Hg and/or diastolic pressure >/= 90 mm Hg), and Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF<50%. Factors to affect oral administration(inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction). Coagulation disfunction,hemorrhagic tendency or receiving anticoagulant therapy>/= CTCAE 2 pneumorrhagia or >/= CTCAE 3 hemorrhage in other organs within 4 weeks. Bone fracture or wounds that was not cured. Arterial thrombus or phlebothrombosis within 12 months and taking anticoagulant agents. Mental diseases and psychotropic substances abuse. Previous treatment with an trial agent within 4 weeks Previous treatment with VEGFR,platelet derived growth factor receptor(PDGFR) TKIs. Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g. Other coexisting malignant disease (except basal-cell carcinoma and carcinoma in situ of uterine cervix).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shunjiang Yu
Phone
+86-021-68868768
Email
yushunjiang@hrs.com.cn
Facility Information:
Facility Name
Department of Medical Oncology, Cancer Center, Sun Yet-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Zhang, MD
Phone
862087343088
Facility Name
Shanghai Pulmonary Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200433
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caicun Zhou, M. D.
Email
caicunzhou@yahoo.com.cn

12. IPD Sharing Statement

Learn more about this trial

Study of Apatinib as 3rd/4th Line Treatment in Patients With Advanced Non-Squamous Non-small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor (EGFR)

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