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

• ClinicalTrials.gov Identifier: NCT00660816
• Recruitment Status: Completed
• First Posted: April 17, 2008
• Results First Posted: August 5, 2014
• Last Update Posted: October 12, 2015
• Sponsor: Case Comprehensive Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Case Comprehensive Cancer Center

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Lung Cancer	Drug: erlotinib hydrochloride; Drug: pemetrexed disodium; Drug: docetaxel	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• 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
• Study Start Date: January 2008
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 :

1. 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
2. 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
3. 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

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

• 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

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
• 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 Posted: April 17, 2008
• 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; Pemetrexed; Erlotinib Hydrochloride; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors