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

• ClinicalTrials.gov Identifier: NCT00950365
• Recruitment Status: Completed
• First Posted: July 31, 2009
• Results First Posted: September 16, 2020
• Last Update Posted: September 16, 2020
• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Cancer Institute (NCI); Eli Lilly and Company; OSI Pharmaceuticals
• Information provided by (Responsible Party): Roman Perez-Soler, Albert Einstein College of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Pemetrexed Disodium	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate progression free survival (PFS) in the schedule-modulated concomitant administration of erlotinib (erlotinib hydrochloride) and pemetrexed (pemetrexed disodium), and in single agent pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) as second-line chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate antitumor objective response rate (complete response [CR] + partial response [PR]) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

II. To evaluate disease control rate (response rate + stable disease, i.e., CR+PR+ stable disease [SD]) and duration of response.

III. To evaluate median time to progression (TTP) and overall survival (OS). IV. To evaluate the safety profile of concurrent pemetrexed and erlotinib versus single agent pemetrexed.

TERTIARY OBJECTIVES:

i. To determine several molecular and cellular biomarkers in the tumors, the skin and the serum that are predictive of the efficacy of pemetrexed and erlotinib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

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

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

After completion of study treatment, patients are followed up for 12 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Schedule-Modulated Concomitant Pemetrexed (Alimta) and Erlotinib (Tarceva) vs Single Agent Pemetrexed (Alimta®) in Patients With Progressive or Recurrent Non-small Cell Lung Cancer (NSCLC)
• Study Start Date: April 2006
• Actual Primary Completion Date: November 17, 2017
• Actual Study Completion Date: November 17, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm A (pemetrexed); 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; Correlative studies; Drug: Pemetrexed Disodium; Given IV; Other Names: 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
Experimental: Arm B (pemetrexed disodium, erlotinib hydrochloride); 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; Given PO; Other Names: Cp-358,774; OSI-774; Tarceva; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Pemetrexed Disodium; Given IV; Other Names: 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

Outcome Measures

Primary Outcome Measures :

1. PFS (Progression Free Survival) [ Time Frame: Time from randomization until documented tumor progression or death from any cause, assessed up to 12 months ]
   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

Secondary Outcome Measures :

1. Objective Response Rate (CR +PR) Evaluated Using RECIST [ Time Frame: Up to 12 months ]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

   Response rates in each arm will be summarized by computing proportions and corresponding 95% confidence intervals.

2. Overall Survival [ Time Frame: Time from the date of randomization to date of death due to any cause, assessed up to 12 months ]
   Time to event endpoints will be analyzed using standard survival analytic methods, including the Kaplan-Meier approach for estimating the survival distributions.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Locations

United States, California

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States, 95817

United States, Massachusetts

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, United States, 01605

United States, New York

Albert Einstein College of Medicine

Bronx, New York, United States, 10461

Bronx River Medical Associates PC

Bronx, New York, United States, 10467

Eastchester Center for Cancer Care

Bronx, New York, United States, 10469

Sponsors and Collaborators

Albert Einstein College of Medicine

National Cancer Institute (NCI)

Eli Lilly and Company

OSI Pharmaceuticals

Investigators

• Principal Investigator: Roman Perez-Soler; Albert Einstein College of Medicine

  Study Documents (Full-Text)

Documents provided by Roman Perez-Soler, Albert Einstein College of Medicine:

Study Protocol and Statistical Analysis Plan  [PDF] April 18, 2011

More Information

• Responsible Party: Roman Perez-Soler, Principal Investigator, Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT00950365
• Other Study ID Numbers: 05-10-277; NCI-2013-01128 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 05277; 05-10-277 ( Other Identifier: Albert Einstein College of Medicine ); P30CA013330 ( U.S. NIH Grant/Contract )
• First Posted: July 31, 2009
• Results First Posted: September 16, 2020
• Last Update Posted: September 16, 2020
• Last Verified: August 2020

Additional relevant MeSH terms:

Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Erlotinib Hydrochloride; Pemetrexed; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors