Clinical trial NCT02066038: Intermittent and Maintenance of Erlotinib in Combination With Pemetrexed/Carboplatin in Ⅲb/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation
Official title: A Multi-center, Open-labeled Phase 2 Study of First Line Intermittent and Maintenance of Erlotinib in Combination With Pemetrexed/Carboplatin in ⅢB/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lung, Carcinoma
Keywords: chemotherapy
maintenance therapy
erlotinib
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
name: Second Affiliated Hospital, Sun Yat-Sen University
First posted: 2014-02-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: EGFR-tyrosine kinase inhibitor(TKI)- ie, erlotinib, gefitinib, has been recommended as the first option for EGFR-mutated IIIb/IV NSCLC by serial trials as it prolonged patients' progression-free survival. The OPTIMAl trial indicated that those who received TKI and chemotherapy during the whole treatment window survived longest. Unfortunately, previous studies(INTACT, TRIBUTE et al) that concurrently combined TKI and cytotoxic regimens failed to improve survival in unselected patients. To avoid the potential synergistic antagonism, the FAST-ACT II trial committed a sequential strategy and find a superiority in the combination arm upon chemotherapy even in EGFR-mutated group. However, pharmaceutically, the continuous administration of an EGFR-TKI before subsequent chemotherapy in FAST-ACT II could obviate the effects of cytotoxic agents due to the erlotinib-induced G1 arrest.

On the basis of these and other studies, the investigators hypothesized that a better sequential combination strategy of EGFR-TKI and chemotherapy (adding a EGFR-TKI wash-out window before chemotherapy) would be more efficacious than chemotherapy alone. In this study, the investigators investigate the efficacy(PFS:progression free survival), safety, and adverse-event profile of chemotherapy plus intermittent and maintenance of erlotinib, when these drugs were used as first-line treatment in who had non-squamous lung carcinoma with EGFR gene mutation in China.


Eligibility criteria: Inclusion Criteria:

* Patients between 18 and 75 years of age.
* Present with histologically proven or cytological diagnosis of non-Squamous NSCLC Stage IIIB or IV as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer, that is not amenable to curative therapy,such as surgery or radiotherapy and so on.
* No prior systemic chemotherapy or targeted therapy for lung cancer before screening.
* Confirmed activating mutation of EGFR-ie, an exon 19 deletion or an exon 21 L858R point mutation.
* Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1.
* Adequate organ function.
* 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 enrollment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment.
* Signed informed consent document on file.
* Estimated life expectancy of ≥12 weeks.
* Patient compliance and geographic proximity that allow adequate follow up.

Exclusion Criteria:

* Known severe hypersensitivity to erlotinib.
* Patients with uncontrolled brain metastasis.
* Pleural effusion or pericardiac effusion that cannot be controlled by drainage or other procedures.
* 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 enrollment.
* Interstitial pneumonia.

Primary outcomes:
measure: Response Evaluation Criteria in Solid Tumors(RECIST) 1.1
timeFrame: eight weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Sun Yat-sen University
name: Hao Long, Prof
role: PRINCIPAL_INVESTIGATOR
References: