A Phase 2 interventional study of pemetrexed disodium and carboplatin in Recurrent Non-small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, sponsored by Vanderbilt-Ingram Cancer Center. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-07-13.
Sponsored by Vanderbilt-Ingram Cancer Center · Phase 2, Interventional, and Treatment
This randomized phase II trial studies how well pemetrexed disodium and carboplatin or cisplatin with or without erlotinib hydrochloride work in treating patients with epidermal growth factor receptor (EGFR) mutant positive stage IV non-small cell lung cancer and acquired resistance to first-line therapy with erlotinib hydrochloride or gefitinib. In patients that develop resistance to first-line therapy with EGFR tyrosine kinase inhibitors (TKIs) the drug is usually stopped and the patient is switched to chemotherapy. Drugs used in chemotherapy, such as pemetrexed disodium, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pemetrexed disodium and carboplatin or cisplatin is more effective with or without erlotinib hydrochloride in treating patients with EGFR mutant non-small cell lung cancer and acquired resistance to EGFR TKIs.
PRIMARY OBJECTIVES:
I. To compare the effects of chemotherapy plus erlotinib (erlotinib hydrochloride) vs. chemotherapy alone on progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients harboring activating endothelial growth factor receptor (EGFR) mutations who developed acquired resistance to first-line therapy with erlotinib or gefitinib.
SECONDARY OBJECTIVES:
I. To determine the overall survival (OS) and response rate in this patient population.
II. To assess the safety of erlotinib in combination with chemotherapy in this patient population.
TERTIARY OBJECTIVES:
I. To determine whether presence of the T790M resistance mutation can be used to predict which patients will benefit from the addition of erlotinib to chemotherapy.
II. To determine if patients with NSCLC harboring activating EGFR mutations who develop acquired resistance to EGFR tyrosine-kinase inhibitors (TKIs) develop additional mutations/genetic alterations on progression.
III. To determine whether any additional biomarkers (e.g., mesenchymal-epithelial transition [MET] amplification, EGFR mutations detected in circulating free deoxyribonucleic acid [DNA]) predict response to second-line therapy in this patient population.
IV. To determine progression-free survival (PFS) in patients on the chemotherapy alone arm who crossed over to erlotinib after progression as compared to patients on the combination chemotherapy arm (erlotinib plus chemotherapy) who switched to chemotherapy of choice (without erlotinib) after progression.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21, pemetrexed disodium intravenously (IV) and carboplatin IV or cisplatin IV on day 1. Treatment repeats every 21 days for 4 courses. Patients then receive maintenance erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21 and pemetrexed disodium IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive pemetrexed disodium and carboplatin or cisplatin as in Arm I. Treatment repeats every 21 days for 4 courses. Patients then receive maintenance pemetrexed disodium as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed until death.
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Adequate hematological function within 7 days of study treatment initiation:
Adequate liver function within 7 days of study treatment initiation:
Adequate renal function within 7 days of study treatment initiation:
a. Serum creatinine \< 1.25 x ULN or calculated creatinine clearance > 50 mL/min (Creatinine clearance may be calculated per institutional standards.)
Exclusion Criteria:
Patients receive erlotinib hydrochloride PO QD on days 1-21, pemetrexed disodium IV and carboplatin IV or cisplatin IV on day 1. Treatment repeats every 21 days for 4 courses. Patients then receive maintenance erlotinib hydrochloride PO QD on days 1-21 and pemetrexed disodium IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: pemetrexed disodium · Drug: carboplatin · Drug: cisplatin · Drug: erlotinib hydrochloride · Other: laboratory biomarker analysis
Patients receive pemetrexed disodium and carboplatin or cisplatin as in Arm I. Treatment repeats every 21 days for 4 courses. Patients then receive maintenance pemetrexed disodium as in Arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: pemetrexed disodium · Drug: carboplatin · Drug: cisplatin · Other: laboratory biomarker analysis
Given IV
Also known as: ALIMTA, LY231514, MTA
Given IV
Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin
Given IV
Also known as: CACP, CDDP, CPDD, DDP
Given PO
Also known as: CP-358,774, erlotinib, OSI-774
Correlative studies
Progression free survival using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
The Kaplan-Meier approach will be used to estimate the time-to-PFS distribution (and median PFS times) for each treatment arm. The stratified log-rank test will be used to compare the PFS distributions between the two treatment arms. The stratified Cox-regression model will be used to estimate the hazard ratio (erlotinib plus chemotherapy vs chemotherapy alone) and corresponding 80% confidence interval (CI).
Time frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year
Overall survival
The Kaplan-Meier approach will be used. The stratified log-rank test will be used to compare the Overall Survival (OS) distributions between the two treatment arms. The stratified Cox-regression model will be used to estimate the hazard ratio (erlotinib plus chemotherapy vs chemotherapy alone) and corresponding 80% confidence interval (CI).
Time frame: From the date of randomization to the date of death from any cause, assessed up to 1 year
Objective response rate defined as partial response (PR) and complete response (CR) using RECIST version 1.1
An estimate of the objective response rate and its 95% CI (Blyth-Still-Casella) will be calculated for each treatment arm. The Mantel-Haenszel chi-squared test stratified according to the factors specified by EGFR activating mutation type (exon 19 deletion vs. exon 21 single point mutation), time to progression on first-line EGFR TKI (≤ 1 year vs. \> 1 year), and ECOG performance status (0 vs. 1) will be used to compare the response rates between the two treatment arms. An unadjusted Fisher's exact test result will also be provided.
Time frame: Up to 1 year
Number of patients with each worst grade toxicity grades 3-5 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
Safety will be assessed through summaries of Adverse Events (AEs), Serious Adverse Events (SAEs), deaths, grade 3 or 4 AEs, AEs with incidence rates greater than 10% (all grades), AE of grade 3 or 4 with incidence rates greater 2%, and changes in laboratory test results. Verbatim descriptions of AEs will be mapped to Medical Dictionary for Regulatory Activities (MedDRA) thesaurus terms
Time frame: Up to 45 days post-treatment
No study locations are listed for this record.
This study is withdrawn, as verified in Jun 2015. You cannot join it, but the record below documents what was studied.
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Vanderbilt-Ingram Cancer Center