Lung Cancer
Conditions
Keywords
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer
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.
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.
Interventions
DRUGerlotinib hydrochloride
Given orally once daily on days 2-19.
DRUGpemetrexed disodium
Given IV over 10 minutes on day 1
DRUGdocetaxel
IV over 60 minutes on day 1.
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 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 | 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) | 36 months after enrollment of last patient | Estimated based on number of evaluable patients with complete response, partial response or stable disease |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Comparator Alimta or Taxotere alone | 24 |
| Experimental Alimta or Taxotere and Tarceva | 22 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Complicating Disease | 0 | 1 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Disease Progression | 16 | 12 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Active Comparator | Total | Experimental |
|---|---|---|---|
| Age, Continuous | 67.0 years FULL_RANGE 11.08 | 65.3 years FULL_RANGE 10.78 | 63.6 years FULL_RANGE 10.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 38 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 20 Participants | 35 Participants | 15 Participants |
| Region of Enrollment United States | 24 participants | 46 participants | 22 participants |
| Sex: Female, Male Female | 19 Participants | 31 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 15 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 24 | 22 / 22 |
| serious Total, serious adverse events | 4 / 24 | 17 / 22 |
Outcome results
Primary
Progression-free Survival
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.
Time frame: 18 months after enrollment of last patient
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Comparator | Progression-free Survival | 5.5 Months |
| Experimental | Progression-free Survival | 4.4 Months |
Secondary
Disease Stabilization Rate (e.g., Complete Response, Partial Response, and Stable Disease)
Estimated based on number of evaluable patients with complete response, partial response or stable disease
Time frame: 36 months after enrollment of last patient
Population: Patients with a complete response, partial response, stable disease, or progressive disease
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Comparator | Disease Stabilization Rate (e.g., Complete Response, Partial Response, and Stable Disease) | 15 participants |
| Experimental | Disease Stabilization Rate (e.g., Complete Response, Partial Response, and Stable Disease) | 16 participants |
Secondary
Overall Survival
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
Time frame: 36 months after enrollment of last patient
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Comparator | Overall Survival | 16.4 Months |
| Experimental | Overall Survival | 14.2 Months |
Secondary
Response Rate
Estimated based on the number of responses by excluding the dropouts who are not evaluable for response using a binomial distribution
Time frame: 36 months after enrollment of last evaluable patient
Population: Patients with a complete response, partial response, stable disease, or progressive disease
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Comparator | Response Rate | 2 participants |
| Experimental | Response Rate | 3 participants |