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Non-small Cell Lung Cancer MetastaticPhase 4NCT02299765

Intercalating and Maintenance Gefitinib in Combination With Chemotherapy for Advanced EGFR-mutant NSCLC

A Phase 4 study testing Gefitinib, gemcitabine and carboplatin in people with Non-small Cell Lung Cancer Metastatic and EGFR Activating Mutation, run by Sichuan University at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Study Title: Intercalating and maintenance Gefitinib in combination with chemotherapy (gemcitabine plus carboplatin) as first-line treatment for patients with advanced EGFR mutation-positive non-small cell lung cancer: A randomized, open-label, multiple-centre study. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Gefitinib, gemcitabine and carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
1 siteChina
Study dates
Dec 2014to Oct 2017
Phase
Phase 4
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

  • Subjects enrolled in this study are required to meet the following inclusion criteria:
  • Patients between 18 and 75 years of age.
  • Patients with histologically or cytologically diagnosed NSCLC,or patients with recurrent advanced NSCLC after surgery.
  • Harboring activating mutation of EGFR,only including an exon 19 deletion or an exon 21 point mutation.
  • Has at least one measureable lesion by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Show all 15Show fewer
  • No prior systemic chemotherapy or targeted therapy for lung cancer before screening except neoadjuvant or adjuvant patients.
  • Adequate organ function, including the following:
  • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.5 × 109/L,platelets ≥100 × 109/L,and hemoglobin ≥9 g/dL.
  • Hepatic: bilirubin ≤1.5 times the upper limit of normal (× ULN),alkaline phosphatase (AP),aspartate transaminase (AST),and alanine transaminase (ALT) ≤3.0 × ULN (AP,AST and ALT ≤5 × ULN is acceptable if the liver has tumor involvement).
  • Renal: calculated creatinine clearance (CrCl) ≥45 mL/minute based on the standard Cockcroft and Gault formula.
  • Prior radiation therapy allowed to <25% of the bone marrow. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study enrolment.
  • Signed informed consent document on file.
  • Estimated life expectancy of ≥12 weeks.
  • Patient compliance and geographic proximity that allow adequate follow up.

Who cannot join

  • Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.
  • Known severe hypersensitivity to gefitinib.
  • Known brain metastasis unless asymptomatic brain metastasis(without neurotic symptoms and sign) and treated with surgery and/or radiation and stable without steroid treatment for at least 2 weeks prior to the first dose of study medication.
  • Pleural effusion or pericardiac effusion that cannot be controlled by drainage or other procedures.
  • Previous treatment with agents targeting the HER axis.
  • Previous systemic antitumour treatment.
Show all 17Show fewer
  • The last regimen of neoadjuvant or adjuvant treatment for non-metastatic disease within 12 months of study treatment.
  • EGFR Resistance mutation (+).
  • Surgery undertaken less than 4 weeks before the study.
  • Inability to comply with protocol or study procedures.
  • A serious concomitant systemic disorder that,in the opinion of the investigator，would compromise the patient's ability to complete the study.
  • A serious cardiac condition,such as myocardial infarction within 6 months,angina,or heart disease.
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
  • Past medical history of Interstitial Lung Disease(ILD),drug induced interstitial disease,radiation pneumonitis which required steroid treatment,or any evidence of clinically active ILD.
  • Pre-existing idiopathic pulmonary fibrosis evidence by CT scan at baseline.
  • Unwillingness to use contraception during the study, women who were pregnant or lactating.
  • Being or planing to participate in other studies.

Trial locations and contacts

1 site in 1 country.

China1 site

  • China West Hospital

    Chengdu, Sichuan, 610000

Other trials in China

About this study

Official title: A Randomized, Open-label, Multiple-centre Study of Intercalating and Maintenance Gefitinib in Combination With Chemotherapy for Advanced NSCLC With EGFR Mutation Positive

Study Title:

Intercalating and maintenance Gefitinib in combination with chemotherapy (gemcitabine plus carboplatin) as first-line treatment for patients with advanced EGFR mutation-positive non-small cell lung cancer: A randomized, open-label, multiple-centre study.

Read more

Target population-Treatment naive EGFR mutant-positive advanced NSCLC patients.

Study Objectives - Primary Study Objective: To investigate whether intercalating and maintenance Gefitinib in combination with chemotherapy improve the Progression-Free Survival (PFS) vs. Gefitinib alone in advanced NSCLC with EGFR activating mutation.

  • Secondary Study Objective： To evaluate whether intercalating and maintenance Gefitinib in combination with chemotherapy improve the Objective Response Rate (ORR), Disease control rate (DCR), Overall survival (OS), 2-year OS rate, QOL vs. Gefitinib alone.

Evaluation the safety of Intercalating and Maintenance Gefitinib in combination with chemotherapy.

  • Exploratory objective: PFS of arm A vs. PFS 1 + PFS 2 of arm B Dynamic biomarker analysis using blood sample a: The PFS 1 of arm B is the time from randomization to disease progression of 1st-line therapy or death from any cause, whichever occurs first. The PFS 2 of arm B is the time from the time of PFS 1 to disease progression of 2nd-line therapy or death from any cause, whichever occurs first.

Study Design-Prospective, open-label, randomized, multi-center study.

Read the detailed description

Study Design:

It is a two-arm, prospective, randomized, open-label, multi-center study. The study will be conducted at 5 study sites in China. West China Hospital serves as the lead site for the study. A total of 146 treatments naive EGFR mutant positive advanced NSCLC patients are planned to be enrolled into this study.

There are four periods in this study: baseline period (≤28days),main phase of treatment (Week 0-Week 16 or until disease progression),post-treatment period and follow-up until about 24 months after the last patients enrolment.

  1. Baseline period: Subject will be enrolled in the study after signing informed consent form (ICF). Investigator will record patient-reported outcome, demographic data and medical history, collect the histological or cytological samples for genetic testing, conduct laboratory examination and perform imaging examination and so on. Notes: The time of imagination is effective within 4 weeks before treatment. The result of haematology, biochemistry and physical examination is effective within 7 days before treatment. Collecting blood one time at screening period (The SOP of blood collection, storage and transportation is in attachment 1).
  2. Main phase of treatment: There are 8 visits during the main phase of treatment study. During the main phase of treatment, investigator conduct laboratory examination, perform imaging examination, assess the tumor status, and evaluate the patient-reported outcome and safety. Collecting blood one time every two cycles (The SOP of blood collection, storage and transportation is in attachment 1).
  3. Post-treatment period: In the study group, investigators will conduct laboratory examination, perform imaging examination, assess the tumor status, and evaluate the patient-reported outcome and safety until disease progression every 8 weeks. And after disease progression investigators will enquire and record survival status of subjects every 8 weeks. In the control group, investigators will conduct laboratory examination, perform imaging examination, assess the tumor status, and evaluate the patient-reported outcome and safety until the first and the second disease progression every 8 weeks. In addition, the information conduct between first disease progression and second progression are optional, but should be collected if available. And after the second disease progression investigators will enquire and record survival status of subjects every 8 weeks. Collecting blood one time every 8 weeks until progress (for control group it will be until the first progress)
  4. Follow-up period:

It will last until about 24 months after the last patients' enrolment. Accesses histological or cytological samples for EGFR testing and related drug resistant gene testing are required. In addition, collection blood is optional, but should be collected if available. All the samples collected during his/her whole life treatment are transported to West China Hospital to store and will be used for further exploratory analysis later.

All results of CT/MRI need to be burned into compact disc (CD). This study will be the first study to compare the efficacy of intercalating and maintenance gefitinib in combination with chemotherapy to gefitinib alone as first-line treatment for patients with advanced EGFR activating mutation-positive non-small cell lung cancer.

Keywords
Advanced Non-small Cell Lung Cancer (NSCLC), EGFR Mutation, gefitinib, chemotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GefitinibDrug

    Also called Iressa

    patients in arm A will be given gefitinib as target therapy

  • gemcitabineDrug

    Also called Gemza

    patients in arm A will be given gemcitabine chemotherapy

  • carboplatinDrug

    Also called Carboplatin Injection

    patients in arm A will be given carboplatin chemotherapy

Study groups in NCT02299765
Study groupRoleWhat they receive
Arm AExperimentalFour cycles gemcitabine(d1,8 ) + carboplatin (d1) + gefitinib (15-25), gefitinib 250mg/d from d15 of last cycle until disease progression. Gemcitabine=1000mg/m2;Carboplatin 5×AUC ; One cycle is 28 days
Receives: Drug: Gefitinib; Drug: gemcitabine; Drug: carboplatin
Arm BActive comparatorGefitinib 250mg/d until disease progression
Receives: Drug: Gefitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival - PFS

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months

Secondary outcomes (2)

  1. Objective Response Rate - ORR

    Measured: at day 42 of treatment

  2. Overall Survival - OS

    Measured: the time from randomization to death from any cause,assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionOct 2017
  4. Study completionOct 2017

Why it stopped: the research data is not statistically significant

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02299765
Sponsor's protocol ID
ISSIRES0109
Status last verified
Nov 2017
First submitted
18 Nov 2014
Last updated
27 Nov 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.

    PubMed 19692680

  • Han JY, Park K, Kim SW, Lee DH, Kim HY, Kim HT, Ahn MJ, Yun T, Ahn JS, Suh C, Lee JS, Yoon SJ, Han JH, Lee JW, Jo SJ, Lee JS. First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol. 2012 Apr 1;30(10):1122-8. doi: 10.1200/JCO.2011.36.8456. Epub 2012 Feb 27.

    PubMed 22370314

  • Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, Natale RB, Schiller JH, Von Pawel J, Pluzanska A, Gatzemeier U, Grous J, Ochs JS, Averbuch SD, Wolf MK, Rennie P, Fandi A, Johnson DH. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1. J Clin Oncol. 2004 Mar 1;22(5):777-84. doi: 10.1200/JCO.2004.08.001.

    PubMed 14990632

  • Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves JA, Wolf MK, Krebs AD, Averbuch SD, Ochs JS, Grous J, Fandi A, Johnson DH. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. J Clin Oncol. 2004 Mar 1;22(5):785-94. doi: 10.1200/JCO.2004.07.215.

    PubMed 14990633

  • Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA; TRIBUTE Investigator Group. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2005 Sep 1;23(25):5892-9. doi: 10.1200/JCO.2005.02.840. Epub 2005 Jul 25.

    PubMed 16043829

  • Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, Milanowski J, Karnicka-Mlodkowski H, Pesek M, Serwatowski P, Ramlau R, Janaskova T, Vansteenkiste J, Strausz J, Manikhas GM, Von Pawel J. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007 Apr 20;25(12):1545-52. doi: 10.1200/JCO.2005.05.1474.

    PubMed 17442998

  • Li T, Ling YH, Goldman ID, Perez-Soler R. Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in human non-small cell lung cancer cells. Clin Cancer Res. 2007 Jun 1;13(11):3413-22. doi: 10.1158/1078-0432.CCR-06-2923.

    PubMed 17545550

  • Cheng H, An SJ, Zhang XC, Dong S, Zhang YF, Chen ZH, Chen HJ, Guo AL, Lin QX, Wu YL. In vitro sequence-dependent synergism between paclitaxel and gefitinib in human lung cancer cell lines. Cancer Chemother Pharmacol. 2011 Mar;67(3):637-46. doi: 10.1007/s00280-010-1347-4. Epub 2010 May 22.

    PubMed 20495920

  • Piperdi B, Ling Y-H, Kroog G, et al. Schedule-dependent interaction between epidermal growth factor inhibitors (EGFRI) and G2/M blocking chemotherapeutic agents (G2/Mb) on human NSCLC cell lines in vitro [J]. J Clin Oncol, 2004; 22: 7028.

  • Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012 Mar 8;366(10):883-892. doi: 10.1056/NEJMoa1113205.

    PubMed 22397650

  • Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. doi: 10.1016/S1470-2045(13)70254-7. Epub 2013 Jun 17.

    PubMed 23782814

  • Yoshimura1 N, Matsuura1 K, Mitsuoka1 S, et al. Gefitinib(G) and pemetrexed（PEM）as a first line treatment in patients with EGFR mutation advanced non-small-cell cancer(NSCLC): a phase II study. ESMO 2012,1258p.

  • Kanda S, Ohe Y, Horinouchi H, et al. Phase II study of gefitinib and inserted cisplatin plus docetaxel as a first-line treatment for advanced non-small cell lung cancer harboring an epidermal growth factor receptor activating mutation. ASCO Abstract, 2013,8064.

  • Choi YJ, Kim SW, Lee DH, et al.Paclitaxel/carboplatin (PC) intercalated with gefitinib or paclitaxel/carboplatin (PC) for advanced non-small cell lung cancer (NSCLC) in selected population who were smoker or wild-type EGFR: Randomized phase II study. ASCO Abstract, 2013, e19079.

  • Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, Esteban E, Molinier O, Brugger W, Melezinek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. doi: 10.1016/S1470-2045(10)70112-1. Epub 2010 May 20.

    PubMed 20493771

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Gefitinib, gemcitabine and carboplatin in people with Non-small Cell Lung Cancer Metastatic and EGFR Activating Mutation, run by Sichuan University 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 17 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: stopped early, as of the sponsor's last update on 27 Nov 2017. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: the research data is not statistically significant). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival - PFS (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02299765, which also lists 19 linked publications.

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 27 Nov 2017.

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