Pemetrexed or Docetaxel With or Without Erlotinib in Stage IIIB or Stage IV Non-Small Cell Lung Cancer - Full Text View

Purpose

RATIONALE: Pemetrexed disodium and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving pemetrexed disodium or docetaxel together with erlotinib hydrochloride is more effective than giving pemetrexed disodium or docetaxel alone in treating non-small lung cancer.

PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium or docetaxel together with or without erlotinib hydrochloride works in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Drug: erlotinib hydrochloride Drug: pemetrexed disodium Drug: docetaxel	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Randomized Phase II Trial, Comparing Standard of Care Chemotherapy (Pemetrexed or Docetaxel) Plus Erlotinib to Standard of Care Chemotherapy (Pemetrexed or Docetaxel) Alone in EGFR TKI-Responsive Non-Small Cell Lung Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Lung Cancer

Drug Information available for: Docetaxel Pemetrexed Pemetrexed disodium Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Progression-free Survival [ Time Frame: 18 months after enrollment of last patient ]
From the date of randomization to the date of disease progression or the date of death, whichever occurs first and censored at the date of last followed for those survivors without disease progression.

Secondary Outcome Measures:

Overall Survival [ Time Frame: 36 months after enrollment of last patient ]
Measured from the date of randomization to the date of death, whichever occurs first and censored at the date of last followed for those survivors
Response Rate [ Time Frame: 36 months after enrollment of last evaluable patient ]
Estimated based on the number of responses by excluding the dropouts who are not evaluable for response using a binomial distribution
Disease Stabilization Rate (e.g., Complete Response, Partial Response, and Stable Disease) [ Time Frame: 36 months after enrollment of last patient ]
Estimated based on number of evaluable patients with complete response, partial response or stable disease


Enrollment:	46
Study Start Date:	January 2008
Study Completion Date:	July 2015
Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients receive pemetrexed disodium IV over 10 minutes OR docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive standard chemotherapy with or without erlotinib hydrochloride in the absence of disease progression or unacceptable toxicity.	Drug: pemetrexed disodium Given IV over 10 minutes on day 1 Other Name: MTA Drug: docetaxel IV over 60 minutes on day 1. Other Name: TXT
Experimental: Arm II Patients receive pemetrexed disodium IV over 10 minutes OR docetaxel IV over 60 minutes on day 1 and erlotinib hydrochloride PO once daily on days 2-19. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive standard chemotherapy with or without erlotinib hydrochloride in the absence of disease progression or unacceptable toxicity.	Drug: erlotinib hydrochloride Given orally once daily on days 2-19. Other Name: erlotinib Drug: pemetrexed disodium Given IV over 10 minutes on day 1 Other Name: MTA Drug: docetaxel IV over 60 minutes on day 1. Other Name: TXT

Arms

Assigned Interventions

Active Comparator: Arm I

Patients receive pemetrexed disodium IV over 10 minutes OR docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive standard chemotherapy with or without erlotinib hydrochloride in the absence of disease progression or unacceptable toxicity.

Drug: pemetrexed disodium

Given IV over 10 minutes on day 1

Other Name: MTA

Drug: docetaxel

IV over 60 minutes on day 1.

Other Name: TXT

Experimental: Arm II

Patients receive pemetrexed disodium IV over 10 minutes OR docetaxel IV over 60 minutes on day 1 and erlotinib hydrochloride PO once daily on days 2-19. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive standard chemotherapy with or without erlotinib hydrochloride in the absence of disease progression or unacceptable toxicity.

Drug: erlotinib hydrochloride

Given orally once daily on days 2-19.

Other Name: erlotinib

Drug: pemetrexed disodium

Given IV over 10 minutes on day 1

Other Name: MTA

Drug: docetaxel

IV over 60 minutes on day 1.

Other Name: TXT

Detailed Description:

OBJECTIVES:

Primary

To evaluate whether maintenance erlotinib hydrochloride added to standard of care (pemetrexed disodium or docetaxel) chemotherapy in patients with erlotinib hydrochloride-responsive advanced non-small cell lung cancer leads to an improved progression-free survival as compared to standard of care pemetrexed disodium or docetaxel alone.

Secondary

To evaluate the effect of maintenance erlotinib hydrochloride on the response rate to standard of care (pemetrexed disodium or docetaxel) therapy in patients with erlotinib hydrochloride-responsive advanced non-small cell lung cancer as compared to standard of care (pemetrexed disodium or docetaxel) alone.
To evaluate whether maintenance erlotinib hydrochloride added to standard of care (pemetrexed disodium or docetaxel) chemotherapy in patients with erlotinib hydrochloride-responsive advanced non-small cell lung cancer leads to an improved overall survival as compared to standard of care (pemetrexed disodium or docetaxel) alone.
To evaluate the effect of maintenance erlotinib hydrochloride on the disease stabilization (complete response [CR] + partial response [PR] + stable disease [SD]) rate to standard of care (pemetrexed disodium or docetaxel) therapy in patients with erlotinib hydrochloride-responsive advanced non-small cell lung cancer as compared to standard of care (pemetrexed disodium or docetaxel) alone.
To evaluate the utility of early positron emission tomography (PET) scanning (baseline versus 1 cycle of protocol therapy) on overall disease assessment and prediction of treatment responsiveness.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to lifetime smoking status (never vs ever) and ECOG performance status (0-1 vs ≥ 2). Patients are randomized to 1 of 2 treatment arms.

Arm I: (standard of care alone): Patients receive pemetrexed disodium intravenously (IV) over 10 minutes OR docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Arm II: (standard of care plus erlotinib): Patients receive pemetrexed disodium IV over 10 minutes OR docetaxel IV over 60 minutes on day 1 and erlotinib hydrochloride orally (PO) once daily on days 2-19. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients may continue to receive standard chemotherapy with or without erlotinib hydrochloride in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks.

Eligibility

Information from the National Library of Medicine

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

Criteria

INCLUSION CRITERIA

Pathologic diagnosis of stage IIIB (with pleural effusion) or IV non-small cell lung cancer
Progression following at least twelve weeks of treatment with single-agent erlotinib (or in combination with other experimental agents) during which time the patients experienced a clinical benefit as assessed by his/her treating physician and corroborated by radiographic assessment (at least one CT scan following at least 4 weeks of erlotinib monotherapy demonstrating stable disease or response on erlotinib therapy).
At least one measurable lesion as defined by modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Life expectancy of at least 12 weeks
Absolute neutrophil count (ANC) >= 1.5x10(9)/L
Platelet count >= 100x 10(9)
Hemoglobin >= 8.0 g/dl
Serum creatinine =< 1.5 upper limit of normal OR calculated creatinine clearance >= 45 mL/min
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
Available baseline diagnostic tumor specimen for correlative studies, any diagnostic material will be acceptable- paraffin block, cell block, fine needle aspirate etc.
Patients must provide verbal and written informed consent to participate in the study
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
Patient must be able to take folic acid, vitamin B12 as well as dexamethasone therapy as per protocol guidelines
Patient must be able to interrupt nonsteroidal anti-inflammatory drugs (NSAIDs) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed (this exclusion criteria applies only to patients who have not received pemetrexed chemotherapy prior)

EXCLUSION CRITERIA

Active central nervous system disease (CNS) metastases, as indicated by clinical symptoms, cerebral edema or progressive growth (subjects with a clinical history of CNS metastases or cord compression are allowable if they have been definitively treated and are clinically stable for at least 4 weeks before first dose of study treatment for prior whole brain radiation and 2 weeks for prior gamma knife therapy)
More than 1 prior cytotoxic chemotherapy regimen for relapsed or metastatic disease (not including erlotinib)
Any prior epidermal growth factor receptor (EGFR) inhibitor therapy except for erlotinib
Major surgery, chemotherapy, or investigational agents within 3 weeks of treatment day 1 (except for erlotinib). Radiation therapy within 2 weeks of treatment day 1 (except for erlotinib).
Prior treatment with both pemetrexed and docetaxel chemotherapy
Pregnancy or breastfeeding or not receiving adequate contraception (including the patients spouse)
Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
Patients who must receive pemetrexed and have the presence of third space fluid which cannot be controlled by drainage
Patients who must receive docetaxel and who have peripheral neuropathy > grade 2
Patients who must receive docetaxel and who have had a hypersensitivity reaction to medications formulated with polysorbate 80

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00660816

Locations


United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
United States, New York
Columbia Presbyterian
New York City, New York, United States, 10032
United States, Ohio
Lake/University Ireland Cancer Center
Cleveland, Ohio, United States, 44060
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, United States, 44122
Southwest General Health Center
Cleveland, Ohio, United States, 44130
UHHS Westlake Medical Center
Cleveland, Ohio, United States, 44145
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Riverside Methodist Hospital
Columbus, Ohio, United States, 43124
Ohio State University
Columbus, Ohio, United States, 43210
UH-Monarch
Mayfield Heights, Ohio, United States, 44124
UH-Firelands
Sandusky, Ohio, United States, 44870

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Afshin Dowlati, MD	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

More Information


Responsible Party:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00660816 History of Changes
Other Study ID Numbers:	CASE2507 P30CA043703 ( U.S. NIH Grant/Contract ) CASE2507 ( Other Identifier: Case Comprehensive Cancer Center ) CASE-2507-CC350 ( Other Identifier: Cancer Center IRB )
First Submitted:	April 16, 2008
First Posted:	April 17, 2008
Results First Submitted:	July 10, 2014
Results First Posted:	August 5, 2014
Last Update Posted:	October 12, 2015
Last Verified:	October 2015

Keywords provided by Case Comprehensive Cancer Center:


recurrent non-small cell lung cancer stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer

Additional relevant MeSH terms:


Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Docetaxel	Erlotinib Hydrochloride Pemetrexed Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Protein Kinase Inhibitors Enzyme Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors