Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer

NCT00950365 | Completed Phase 2 Results DMC

• 4 other identifiers: 05-10-277NCI-2013-0112805277P30CA013330
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 5

Brief Summary

This randomized phase II trial studies how well pemetrexed disodium with or without erlotinib hydrochloride works in treating patients with stage IIIB-IV or recurrent non-small cell lung cancer. Drugs used in chemotherapy, such as pemetrexed disodium, 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 is more effective with or without erlotinib hydrochloride in treating non-small cell lung cancer.

Conditions

Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• PFS (Progression Free Survival)

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  Time from randomization until documented tumor progression or death from any cause, assessed up to 12 months

Secondary Outcomes (2)

• Objective Response Rate (CR +PR) Evaluated Using RECIST

  Up to 12 months

• Overall Survival

  Time from the date of randomization to date of death due to any cause, assessed up to 12 months

Study Arms (2)

Arm A (pemetrexed)

ACTIVE COMPARATOR

Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Pemetrexed Disodium

Arm B (pemetrexed disodium, erlotinib hydrochloride)

EXPERIMENTAL

Patients receive pemetrexed disodium IV as in Arm A and erlotinib hydrochloride PO QD on days 2-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Pemetrexed Disodium

Interventions

Erlotinib Hydrochloride DRUG

Given PO

Also known as: Cp-358,774, OSI-774, Tarceva

Arm B (pemetrexed disodium, erlotinib hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (pemetrexed); Arm B (pemetrexed disodium, erlotinib hydrochloride)

Pemetrexed Disodium DRUG

Given IV

Also known as: Alimta, LY231514, N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Arm A (pemetrexed); Arm B (pemetrexed disodium, erlotinib hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed advanced (stage IIIB with a malignant pleural effusion or stage IV disease) or recurrent nonsquamous NSCLC
• Patients must have at least one measurable disease per RECIST criteria; all sites of disease must be assessed within 4 weeks prior to registration
• Patient must have disease progression after one prior combinational chemotherapy and/or targeted therapy other than pemetrexed or an epidermal growth factor receptor (EGFR) ) tyrosine kinase inhibitor (TKI) (such as erlotinib, gefitinib, or a second generation EGFR TKI); prior monoclonal antibody against EGFR is allowed) for metastatic disease, or relapse while receiving adjuvant therapy, or within 12 months of completing adjuvant therapy
• All patients will be screened for brain metastasis within 6 weeks prior to registration; patients with treated and stable brain metastases must have been treated with surgery and/or radiation and are asymptomatic and are no longer taking corticosteroids
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 or Karnofsky \>= 60%
• Absolute neutrophil count \>= 1,500/uL
• Hemoglobin \>= 8.0 g/dL
• Platelets \>= 100,000/uL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN), except in known hepatic metastasis, wherein may be =\< 3.0 X ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN, except in known hepatic metastasis, wherein may be =\< 5.0 X ULN
• Creatinine clearance \>= 45 mL/min for patients with creatinine levels above institutional normal
• Patients must not be pregnant or breastfeeding since there is no information regarding the use of these agents in this population; a negative serum or urine pregnancy test is required within 14 days prior to registration if pre- or perimenopausal (i.e., last menstrual period within one year of registration); both pemetrexed and erlotinib are Class D agent with the potential for teratogenic or abortifacient effects; patients both females and males with reproductive potential (i.e. menopausal for less than 1 year and not surgically sterilized) must practice contraceptive measures throughout the study
• Patients taking Warfarin or nonsteroidal anti-inflammatory drugs (NSAIDs) are eligible; patients with mild to moderate renal insufficiency should avoid taking NSAIDs with short elimination half-lives for a period of 2 days before, the day of, and 2 days following administration of Alimta; if the patient is taking other cytochrome P450 3A4 (CYP3A4) inducers or inhibitors, they must be discontinued at least one week prior to starting erlotinib
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have had immunotherapy, hormone, chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who have received pemetrexed or an EGFR TKI (such as erlotinib, gefitinib, or a second generation anti-EGFR TKI) for their metastatic disease should be excluded from this clinical trial; other molecularly targeted agent, including monoclonal antibody or vaccine against EGFR or angiogenesis inhibitor, is allowed
• Patients may not be receiving any other investigational or commercial agents or therapies other than those described below with the intent to treat the patient's malignancy
• Patients with uncontrolled brain metastases should be excluded from this clinical trial because of their poor prognosis
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib or pemetrexed or other agents used in the study
• Patients with gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease, are ineligible
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (such as bacteremia or active hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with erlotinib or pemetrexed or other agents administered during the study; appropriate studies will be undertake in patients receiving combination anti-retroviral therapy when indicated

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• National Cancer Institute (NCI): collaborator
• Eli Lilly and Company: collaborator
• OSI Pharmaceuticals: collaborator

Study Sites (5)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, 01605, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Bronx River Medical Associates PC

The Bronx, New York, 10467, United States

Location

Eastchester Center for Cancer Care

The Bronx, New York, 10469, United States

Location

MeSH Terms

Conditions

Adenocarcinoma, Bronchiolo-Alveolar; Adenocarcinoma of Lung; Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Pemetrexed

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Roman Perez-Soler, MD
• Organization: Montefiore Medical Center

RPEREZSO@montefiore.org

(718) 405-8505

Study Officials

• Roman Perez-Soler

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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 Investigator

Study Record Dates

• First Submitted: July 30, 2009
• First Posted: July 31, 2009
• Study Start: April 1, 2006
• Primary Completion: November 17, 2017
• Study Completion: November 17, 2017
• Last Updated: September 16, 2020
• Results First Posted: September 16, 2020

Record last verified: 2020-08

Locations

US (5)