Pemetrexed Disodium and Carboplatin or Cisplatin With or Without Erlotinib Hydrochloride in Treating Patient With Stage IV Non-Small Cell Lung Cancer Resistant to First-Line Therapy With Erlotinib Hydrochloride or Gefitinib

NCT01928160 | Withdrawn Phase 2 DMC

• 3 other identifiers: VICC THN 1303NCI-2013-01385P30CA068485
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Recurrent Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer, EGFR mutation, erlotinib acquired resistance

Outcome Measures

Primary Outcomes (1)

• 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).

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year

Secondary Outcomes (3)

• Overall survival

  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

  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

  Up to 45 days post-treatment

Study Arms (2)

Arm I (chemotherapy, erlotinib hydrochloride)

EXPERIMENTAL

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

Arm II (chemotherapy)

EXPERIMENTAL

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

Interventions

pemetrexed disodium DRUG

Given IV

Also known as: ALIMTA, LY231514, MTA

Arm I (chemotherapy, erlotinib hydrochloride); Arm II (chemotherapy)

carboplatin DRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Arm I (chemotherapy, erlotinib hydrochloride); Arm II (chemotherapy)

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Arm I (chemotherapy, erlotinib hydrochloride); Arm II (chemotherapy)

erlotinib hydrochloride DRUG

Given PO

Also known as: CP-358,774, erlotinib, OSI-774

Arm I (chemotherapy, erlotinib hydrochloride)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (chemotherapy, erlotinib hydrochloride); Arm II (chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to initiation of any study-specific procedure or treatment. Informed Consent Form must be signed within 14 days of study treatment initiation.
• Age \> 18 years
• Able and willing to comply with the protocol
• Histologically- or cytologically-confirmed Stage IV NSCLC with an EGFR exon-19 deletion or L858R mutation
• Must have received at least 6 months of first-line therapy with erlotinib or gefitinib
• Clinical evidence of progression on first-line EGFR TKI therapy
• Adequate hematological function within 7 days of study treatment initiation:
• Absolute neutrophil count (ANC) \> 1.5 x 109/L AND
• Platelet count \> 100 x 109/L AND
• Hemoglobin \> 9 g/dL (may be transfused to maintain or exceed this level)
• Adequate liver function within 7 days of study treatment initiation:
• Total bilirubin \< 1.5 x upper limit of normal (ULN) AND
• AST and ALT \< 2.5 x ULN in patients without liver metastases; \< 5 x ULN in patients with liver metastases
• 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.)

You may not qualify if:

• Any other prior treatment for metastatic NSCLC other than erlotinib or gefitinib. Prior adjuvant chemotherapy or concurrent chemo-radiation therapy is allowed if completed at least 12 months prior to trial enrollment
• Radiotherapy to the brain within 28 days prior to randomization, or radiotherapy to any other site up to 14 days prior to randomization
• Clinically significant (i.e., active) cardiovascular disease (e.g., cerebrovascular accident or myocardial infarction within 6 months prior to randomization), unstable angina, congestive heart failure (New York Heart Association Class \> II), or serious cardiac arrhythmia, that is uncontrolled by medication or may interfere with administration of study treatment
• Treatment with any other investigational agent or participation in another clinical trial that combines erlotinib with a second therapy unless the patient was on placebo.
• Malignancies other than NSCLC within 3 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with radiation or surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
• Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Carboplatin; Cisplatin; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Quinazolines

Study Officials

• Leora Horn

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal InvestigatorAssistant Professor of Medicine; Assistant Director, Educator Development Program; Clinical Director, Thoracic Oncology Program; Medical Oncologist

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: August 23, 2013
• Study Start: June 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: July 13, 2015

Record last verified: 2015-06