Non-small-cell Lung CancerPhase 2NCT03267654
Gefitinib With Chemotherapy or Anti-angiogenesis in NSCLC Patients With Bim Deletion or Low EGFR Mutation Abundance
A Phase 2 study testing gefitinib combined with chemotherapy, gefitinib combined with apatinib and gefitinib single agent in people with Non-small-cell Lung Cancer, run by Qilu Pharmaceutical Co., Ltd. at 1 site in China.
Trial summary
This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-small-cell Lung Cancer
- What is being tested?
- gefitinib combined with chemotherapy, gefitinib combined with apatinib and gefitinib single agent
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 12 Oct 2017to 30 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Volunteered for attending the study, and signed informed consent form (ICF)to participate in the study.
- Cytologically and Histologically documented, locally advanced or recurrent or metastatic (stage IIIb, IIIc, IV) non-small cell lung cancer patients .
- EGFR mutation (exon 19 deletion or exon 21 L858R) with Bim deletion or low abundance for EGFR mutation.
- Age range: 18 years to 75 years.
- Patients must have measurable lesion according to the RECIST (version 1.1) criteria.
- Life expectancy of ≥ 12 weeks
Show all 15Show fewer
- ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 1.
- Patients hadn't received past system treatment, including cytotoxic drugs; For patients who have received adjuvant or neoadjuvant chemotherapy appears recurrence or metastasis more than 6 months from accepting the last dose of chemotherapy drugs
- Adequate organ function as defined by the following criteria:
- Bone marrow function: absolute neutrophil count ≥ 1,500,000,000/L and platelet count ≥100,000,000,000/L and hemoglobin ≥9g/dL.
- Liver function: Total bilirubin ≤ 1.5 ULN (upper limit of normal). AP (alkaline phosphatase), AST ( aspartate aminotransferase) and ALT (alanine transaminase) ≤ 3 ULN in the absence of liver metastases or up to 5 ULN in case of liver metastases.
- Renal function: creatinine clearance ≥ 60 ml/min. (based on modified Cockcroft-Gault formula).
- INR （international normalized ratio）≤ 1.5, and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 ULN.
- For all females of childbearing potential a negative serum/urine pregnancy test must be obtained within 48 hours before enrollment. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential.
- Fertile men and women must use effective contraception.
Who cannot join
- Histology confirmed for squamous carcinomas, including mixed gland scale cancer, small cell lung cancer.
- Poor controlled hypertension, it means systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg after drug therapy.
- There are imaging evidence of tumor invading or closing to the pulmonary vessels (e.g., pulmonary artery, superior vena cava).
- Thrombosis in 6 months before enrollment, including pulmonary thrombosis or deep venous thrombosis., or patient had medical evidence or history of thrombosis or bleeding tendency regardless of the severity.
- Patients with medical history of hemoptysis (defined as about 2.5ml bright blood) 2 weeks before the enrollments.
- Proteinuria ≥++, or 24h proteinuria ≥1.0g.
Show all 21Show fewer
- A uncontrolled clinical infection, activity, including but not limited to acute pneumonia.
- Patients with known liver disease: the hepatitis B virus (HBV) infection and hepatitis b virus DNA (HBV DNA) ≥ 500 copy number or ≥100 IU/ml; or more; or hepatitis C virus (HCV) infection; or liver cirrhosis, etc.
- Patients who are at risk of human immunodeficiency virus (HIV) or syphilis infection.
- Patients who have a difficulty in swallowing or drug absorption.
- There are diseases of alimentary canal such as active duodenal ulcer, the ulcerous colitis, intestinal obstruction or other conditions which can cause gastrointestinal bleeding or perforation in the investigator's opinion; or patient has a history of intestinal perforation, intestinal fistula.
- Evaluation of cardiac function: left ventricular ejection fraction < 50% (echocardiography); Moderate or above disorders of mitral valve and tricuspid shut down;, serious/unstable angina or acute myocardial infarction coronary artery bypass surgery in 6 months before enrollment; patients with class 2 and above cardiac dysfunction according to New York heart association (NYHA) classification
- Stroke and transient ischemic in 12 months before enrollment.
- severe ulcer in the skin wound, trauma and mucosa or fractures have been not fully healed.
- Patients received CYP3A4 strong inhibitor and/or inducer in 2 weeks before enrollment; Patients received P-gp and breast cancer resistance protein (BCRP) substrates drug in 2 weeks before enrollment.
- Patients received other anti-tumor treatment at the same time.
- Patients exist serious psychological or mental abnormalities, so patient compliance is not sufficient.
- Poorly controlled serous cavity effusion, including but not limited to malignant pleural effusion, malignant pericardial effusion and malignant peritoneal effusion.
- Patients have a weight loss (≥10%) within 6 weeks before enrollment.
- The pregnancy of female patients test is positive or lactation women.
- Patients haven't been diagnosed other malignant disease, except the basal cell carcinoma and cervical carcinoma.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Pulmonary Hospital;
Shanghai, Shanghai Municipality, 200000
Caicun Zhou, MD
About this study
Official title: Gefitinib Versus Combination of Gefitinib With Chemotherapy or Anti-angiogenesis as 1st Line Treatment in Advanced NSCLC Patients Detected With Bim Deletion or Low EGFR Activating Mutation Abundance：A Randomized, Multicentre, Phase II Study
This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutation (exon 19 deletion or exon 21 L858R point mutation), accompanied with Bim deletion or low activating EGFR mutation abundance.
Read the detailed description
BIM (bcl-2 interacting mediator of cell death) deletion polymorphism and low EGFR mutation abundance were poor clinical response markers to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients who had EGFR mutations.This is a phase II clinical trial to investigate the efficacy of combination treatment for patients harboring above risk factors.
Advanced EGFR mutated NSCLC Patients with Bim deletion or EGFR low mutation abundance were randomized divided into following three treatment groups:
A: gefitinib 250mg Qd combined with doublet chemotherapy: pemetrexed (500mg/m²，day 1 ，intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days.
B: gefitinib 250mg Qd combined with apatinib 250mg/d intravenously per 21 days. C: gefitinib 250mg Qd
- Conditions
- Non-small-cell Lung Cancer
- Being tested
- gefitinib combined with chemotherapy, gefitinib combined with apatinib, gefitinib single agent
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gefitinib combined with chemotherapyDrug
Also called yiruike
Gefitinib 250mg, p.o., q.d., continuous regimens on an empty stomach or after meal for 2 hours until disease progression, intolerable toxicity or patient withdraw ICF.
Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days. Every 3 weeks is a chemotherapy cycle, and 4 chemotherapy cycles is maximum limit.
gefitinib combined with apatinibDrug
Also called yiruike
gefitinib 250mg, p.o., q.d., continuous regimens on an empty stomach or after meal for 2 hours.
Apatinib 250mg, p.o., q.d. per 21 days. until disease progression, intolerable toxicity, patient withdraw ICF or death.
gefitinib single agentDrug
Also called yiruike
Patients received Gefitinib 250mg q.d. orally until disease progression, intolerable toxicity or death.
| Study group | Role | What they receive |
|---|---|---|
| gefitinib combined with chemotherapy | Experimental | gefitinib 250mg Qd combined with pemetrexed plus carboplatin: pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days. Receives: Drug: gefitinib combined with chemotherapy |
| gefitinib combined with apatinib | Experimental | gefitinib 250mg Qd combined with apatinib 250mg per 21 days Receives: Drug: gefitinib combined with apatinib |
| gefitinib single agent | Active comparator | Advanced NSCLC patients with EGFR activating mutation (L858R, 19Del) received gefitinib 250mg Qd orally until progression, intolerable toxicity or death. Receives: Drug: gefitinib single agent |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
From start of anti-cancer therapy until progression or death
Measured: 8 weeks
Secondary outcomes (6)
overall survival
evaluated in the 36th since treatment begain
Measured: 36 months
objective response rate
Evaluated the rate of complete response and partial response in the 8 weeks since treatment began
Measured: 8 weeks
disease control rate
Evaluated the rate of complete response，partial response and stable disease in the 8 weeks since anti-cancer therapy
Measured: 8 weeks
duration of response
interval between the time which complete response or partial response happened and progressive disease or death
Measured: 8 weeks
safety evaluation
Safety observation indexes were listed as following: adverse events and serious adverse events (according to CommonTerminology Criteria Adverse Events Version 4.03), physical exam, vital signs(blood pressure, heart rate, respiratory rate,body temperature), weight variation, laboratory examination(hematology, blood biochemistry, urinalysis and so on), electrocardiograph(ECG),ultrasonic cardiogram(UCG), ect.
Measured: 8 weeks
compare quality of life
Quality of Life Questionnaire(including QLQ-C30 and QLQ-LC13) evaluated since treatment began.At the end of the trial, the differences between the two indicators were compared with Mixed-effects model repeated measures (MMRM), where the baseline was scored as a covariant and the treatment group as a fixed variable. In addition, the baseline values of the two scores, the value of each visit, and the change value of the baseline were statistically described.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2017
- Study start12 Oct 2017
- Primary completion20 Oct 2020 (estimated)
- Study completion30 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small-cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Qilu Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qilu Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Caicun Zhou, Principal investigator, Shanghai Pulmonary Hospital, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03267654
- Sponsor's protocol ID
- SHENKANG
- Status last verified
- Jul 2020
- First submitted
- 14 Aug 2017
- Last updated
- 3 Aug 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gefitinib Versus Combination of Gefitinib With Chemotherapy or Anti-angiogenesis as 1st Line Treatment in Advanced NSCLC Patients Detected With Bim Deletion or Low EGFR Activating Mutation Abundance：A Randomized, Multicentre, Phase II Study
- ClinicalTrials.gov ID
- NCT03267654
- Acronym / sponsor ID
- SHENKANG
- Conditions
- Non-small-cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Qilu Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 12 Oct 2017 (actual)
- Primary completion
- 20 Oct 2020 (estimated)
- Study completion
- 30 Dec 2021 (estimated)
- First posted
- 30 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutation (exon 19 deletion or exon 21 L858R point mutation), accompanied with Bim deletion or low activating EGFR mutation abundance.
Detailed description
BIM (bcl-2 interacting mediator of cell death) deletion polymorphism and low EGFR mutation abundance were poor clinical response markers to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients who had EGFR mutations.This is a phase II clinical trial to investigate the efficacy of combination treatment for patients harboring above risk factors.
Advanced EGFR mutated NSCLC Patients with Bim deletion or EGFR low mutation abundance were randomized divided into following three treatment groups:
A: gefitinib 250mg Qd combined with doublet chemotherapy: pemetrexed (500mg/m²，day 1 ，intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days.
B: gefitinib 250mg Qd combined with apatinib 250mg/d intravenously per 21 days. C: gefitinib 250mg Qd
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| gefitinib combined with chemotherapy | Experimental | Drug: gefitinib combined with chemotherapygefitinib 250mg Qd combined with pemetrexed plus carboplatin: pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days. |
| gefitinib combined with apatinib | Experimental | Drug: gefitinib combined with apatinibgefitinib 250mg Qd combined with apatinib 250mg per 21 days |
| gefitinib single agent | Active comparator | Drug: gefitinib single agentAdvanced NSCLC patients with EGFR activating mutation (L858R, 19Del) received gefitinib 250mg Qd orally until progression, intolerable toxicity or death. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Volunteered for attending the study, and signed informed consent form (ICF)to participate in the study.
- Cytologically and Histologically documented, locally advanced or recurrent or metastatic (stage IIIb, IIIc, IV) non-small cell lung cancer patients .
- EGFR mutation (exon 19 deletion or exon 21 L858R) with Bim deletion or low abundance for EGFR mutation.
- Age range: 18 years to 75 years.
- Patients must have measurable lesion according to the RECIST (version 1.1) criteria.
Key exclusion criteria (21 listed)
- Histology confirmed for squamous carcinomas, including mixed gland scale cancer, small cell lung cancer.
- Poor controlled hypertension, it means systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg after drug therapy.
- There are imaging evidence of tumor invading or closing to the pulmonary vessels (e.g., pulmonary artery, superior vena cava).
- Thrombosis in 6 months before enrollment, including pulmonary thrombosis or deep venous thrombosis., or patient had medical evidence or history of thrombosis or bleeding tendency regardless of the severity.
- Patients with medical history of hemoptysis (defined as about 2.5ml bright blood) 2 weeks before the enrollments.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gefitinib combined with chemotherapyAlso: yiruikeGefitinib 250mg, p.o., q.d., continuous regimens on an empty stomach or after meal for 2 hours until disease progression, intolerable toxicity or patient withdraw ICF. Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days. Every 3 weeks is a chemotherapy cycle, and 4 chemotherapy cycles is maximum limit. | Drug | gefitinib combined with chemotherapy |
| gefitinib combined with apatinibAlso: yiruikegefitinib 250mg, p.o., q.d., continuous regimens on an empty stomach or after meal for 2 hours. Apatinib 250mg, p.o., q.d. per 21 days. until disease progression, intolerable toxicity, patient withdraw ICF or death. | Drug | gefitinib combined with apatinib |
| gefitinib single agentAlso: yiruikePatients received Gefitinib 250mg q.d. orally until disease progression, intolerable toxicity or death. | Drug | gefitinib single agent |
Primary outcome
Progression free survival
Time frame: 8 weeks
From start of anti-cancer therapy until progression or death
6 secondary outcomes
overall survival
Time frame: 36 months
objective response rate
Time frame: 8 weeks
disease control rate
Time frame: 8 weeks
duration of response
Time frame: 8 weeks
safety evaluation
Time frame: 8 weeks
compare quality of life
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2020.
Related trials for Non-small-cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Caicun Zhou principal investigator
Shanghai Pulmonary Hospital, Shanghai, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing gefitinib combined with chemotherapy, gefitinib combined with apatinib and gefitinib single agent in people with Non-small-cell Lung Cancer, run by Qilu Pharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Caicun Zhou, MD (+8613301825532, caicunzhoudr@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2020.