Non-small Cell Lung Cancer
Conditions
Keywords
Stage IIIB/IV non-small cell lung cancer, Non-small cell lung cancer, NSCLC, Lung Cancer, Pralatrexate, Erlotinib, Tarceva, PDX, Smoking, Smoker
Brief summary
The purpose of this clinical study is to determine the effectiveness (ability to provide beneficial treatment of the disease) and safety of pralatrexate compared to erlotinib when given to non-small cell lung cancer (NSCLC) patients who are current or former cigarette smokers and who have received at least 1 prior treatment with a platinum drug (cisplatin or carboplatin)
Interventions
DRUGPralatrexate
Intravenous (IV) push administration over 3-5 minutes into a patent IV line containing normal saline (0.9% sodium chloride). Initial dose: 230 mg/m2, increased to 270 mg/m2 if patient does not have specific adverse events (AEs) as per the protocol after receipt of 2 consecutive doses 2 weeks apart. Reductions allowed in 40 mg/m2 decrements to 190 mg/m2 per the protocol defined dose modifications. Protocol amended dose: 190 mg/m2, then 230 mg/m2 if patient does not have specific AEs per the protocol after receipt of 2 consecutive doses 2 weeks apart. Reductions allowed in 40 mg/2 decrements to 150 mg/m2 per the protocol defined dose modifications. Administered on days 1 and 15 of a 4-week cycle (every 2 weeks) until criteria for discontinuation per the protocol are met.
DRUGErlotinib
150 mg orally in tablet form Administered daily 1 hour before or 2 hours after ingestion of food until criteria for discontinuation per the protocol are met.
DIETARY_SUPPLEMENTVitamin B12
1 mg intramuscular injection Administered within 10 weeks of randomization, every 8-10 weeks throughout the study and for at least 30 days after last dose of study treatment.
DIETARY_SUPPLEMENTFolic Acid
1-1.25 mg orally Administered daily for at least 7 days prior to randomization, throughout the study and for at least 30 days after last dose of study treatment.
Sponsors
Spectrum Pharmaceuticals, Inc
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
* Confirmed Stage IIIB/ IV non-small cell lung cancer (NSCLC). * Relapsed after treatment with 1 or 2 prior chemotherapy regimens, including at least 1 platinum-based treatment. Patients may have received pemetrexed as 1 of the prior therapies. Patients may not have received investigational therapy as their only prior therapy. * Recovered from the toxic effects of prior therapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Smoked ≥ 100 cigarettes in their lifetime, whether a former or current cigarette smoker. * Adequate blood, liver and kidney function as defined by laboratory values. * Received 1-1.25 mg daily oral folic acid for at least 7 days prior to randomization and 1 mg intramuscular injection of vitamin B12 within 10 weeks prior to randomization. * Women of childbearing potential must use medically acceptable birth control and have a negative serum pregnancy test within 14 days prior to randomization. Patients who are postmenopausal for at least 1 year (\> 12 months since last menses) or are surgically sterilized do not require this test. * Men who are not surgically sterile must use medically safe and effective birth control from the time of study randomization, and agree to continue practicing until at least 90 days after the last administration of study treatment. * Accessible for repeat dosing and follow-up. * Give written informed consent.
Exclusion criteria
* Active concurrent primary malignancy (except non-melanoma skin cancer or in situ carcinoma of the cervix). If there is a history of prior malignancy, the patient must be disease-free for ≥ 5 years. Patients with other prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no evidence of active or recurrent disease. * Use of investigational drugs, biologics, or devices within 4 weeks prior to randomization. * Previous exposure to pralatrexate or erlotinib. * Women who are pregnant or breastfeeding. * Congestive Heart Failure Class III/IV according to New York Heart Association (NYHA) Functional Classification. * Uncontrolled hypertension. * Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of \<100 mm3 or detectable viral load within the past 3 months, and is receiving combination anti-retroviral therapy. * Symptomatic central nervous system metastases or lesions for which treatment is required. * Major surgery within 2 weeks of study randomization. * Receipt of any conventional systemic chemotherapy within 4 weeks (6 weeks for nitrosoureas, mitomycin C), or radiation therapy (RT) within 2 weeks, prior to randomization. * Active infection or any serious underlying medical condition, which would impair the ability of the patient to receive protocol treatment. * Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent or limit study compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) of Patients Receiving Pralatrexate vs. Erlotinib | Assessed from date of randomization no less frequently than every 16 weeks for up to 2 years after randomization. | OS was defined as the length of time from randomization until death due to any cause. Patients who were alive at the time of the data cut-off date were censored at the last contact date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Assessed every 8 weeks for the first 24 weeks, then every 16 weeks for up to 2 years or until PD or start of subsequent treatment. | Number of patients whose tumors responded to Pralatrexate or Erlotinib, using the Response Criteria in Solid Tumors (RECIST). |
| Progression-free Survival (PFS) of Patients Receiving Pralatrexate vs. Erlotinib | Assessed every 8 weeks for the first 24 weeks, then every 16 weeks for up to 2 years or until PD or start of subsequent treatment. | PFS was calculated as the number of days from randomization to the date of radiological evidence of PD or death due to any cause. |
| Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). | — |
Countries
Argentina, Brazil, Czechia, Hungary, India, United States
Participant flow
Recruitment details
Patients were enrolled between January 2008 and June 2009 across 43 study sites in 6 countries.
Participants by arm
| Arm | Count |
|---|---|
| Pralatrexate | 100 |
| Erlotinib | 101 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization | Randomized but not treated | 3 | 0 |
| Treatment | Treatment ongoing at time of data cutoff | 0 | 3 |
Baseline characteristics
| Characteristic | Total | Pralatrexate | Erlotinib |
|---|---|---|---|
| Age, Continuous | 63.0 years STANDARD_DEVIATION 9 | 63.0 years STANDARD_DEVIATION 9 | 62.0 years STANDARD_DEVIATION 9.1 |
| Age, Customized >=65 years | 83 participants | 42 participants | 41 participants |
| Age, Customized Between 18 and 65 years | 118 participants | 58 participants | 60 participants |
| Region of Enrollment Argentina | 19 participants | 11 participants | 8 participants |
| Region of Enrollment Brazil | 22 participants | 13 participants | 9 participants |
| Region of Enrollment Czech Republic | 37 participants | 17 participants | 20 participants |
| Region of Enrollment Hungary | 32 participants | 17 participants | 15 participants |
| Region of Enrollment India | 23 participants | 11 participants | 12 participants |
| Region of Enrollment United States | 68 participants | 31 participants | 37 participants |
| Sex: Female, Male Female | 64 Participants | 31 Participants | 33 Participants |
| Sex: Female, Male Male | 137 Participants | 69 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 91 / 97 | 94 / 101 |
| serious Total, serious adverse events | 31 / 97 | 32 / 101 |
Outcome results
Primary
Overall Survival (OS) of Patients Receiving Pralatrexate vs. Erlotinib
OS was defined as the length of time from randomization until death due to any cause. Patients who were alive at the time of the data cut-off date were censored at the last contact date.
Time frame: Assessed from date of randomization no less frequently than every 16 weeks for up to 2 years after randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pralatrexate | Overall Survival (OS) of Patients Receiving Pralatrexate vs. Erlotinib | 6.7 Months Survival |
| Erlotinib | Overall Survival (OS) of Patients Receiving Pralatrexate vs. Erlotinib | 7.0 Months Survival |
95% CI: [0.61, 1.14]
Secondary
Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib
Time frame: Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal).
Population: Adverse Events (AEs) and Serious AEs (SAEs) are presented regardless of causality for patients who received at least one dose of Pralatrexate or Erlotinib. Events were graded by the investigator using the NCI CTCAE Scale (version 3.0) which provides a grading scale for each AE term.~Grade 3 = Severe~Grade 4 = Life-threatening or disabling
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pralatrexate | Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | At least one AE | 75 Treated Participants |
| Pralatrexate | Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | Grade 3 AEs | 25 Treated Participants |
| Pralatrexate | Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | Grade 4 AEs | 5 Treated Participants |
| Pralatrexate | Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | At least one SAE | 14 Treated Participants |
| Erlotinib | Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | At least one SAE | 2 Treated Participants |
| Erlotinib | Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | At least one AE | 77 Treated Participants |
| Erlotinib | Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | Grade 4 AEs | 0 Treated Participants |
| Erlotinib | Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib | Grade 3 AEs | 18 Treated Participants |
Secondary
Progression-free Survival (PFS) of Patients Receiving Pralatrexate vs. Erlotinib
PFS was calculated as the number of days from randomization to the date of radiological evidence of PD or death due to any cause.
Time frame: Assessed every 8 weeks for the first 24 weeks, then every 16 weeks for up to 2 years or until PD or start of subsequent treatment.
Population: Patients who were alive without a disease response assessment of PD as of the data cut-off date were censored at the last disease assessment date or the date of randomization, whichever was later. Patients with no response assessments after baseline were censored at date of randomization resulting in a duration of PFS of 1 day.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pralatrexate | Progression-free Survival (PFS) of Patients Receiving Pralatrexate vs. Erlotinib | 3.4 months |
| Erlotinib | Progression-free Survival (PFS) of Patients Receiving Pralatrexate vs. Erlotinib | 2.8 months |
Secondary
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib
Number of patients whose tumors responded to Pralatrexate or Erlotinib, using the Response Criteria in Solid Tumors (RECIST).
Time frame: Assessed every 8 weeks for the first 24 weeks, then every 16 weeks for up to 2 years or until PD or start of subsequent treatment.
Population: Based on all treated patients with measurable disease at baseline. Patients who were declared unevaluable for response were considered nonresponders and were included in the calculation of response rate. Patients were unevaluable if they were off-treatment prior to first response assessment, never received treatment or had unconfirmed responses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pralatrexate | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Complete + Partial Response | 2 Participants |
| Pralatrexate | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Progressive Disease (PD) | 29 Participants |
| Pralatrexate | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Partial Response (PR) | 2 Participants |
| Pralatrexate | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Disease Control (CR+PR+SD) | 35 Participants |
| Pralatrexate | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Complete Response (CR) | 0 Participants |
| Pralatrexate | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Stable Disease (SD) | 33 Participants |
| Pralatrexate | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Missing (off or no treatment, not confirmed) | 31 Participants |
| Pralatrexate | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Unable to Evaluate | 2 Participants |
| Erlotinib | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Missing (off or no treatment, not confirmed) | 20 Participants |
| Erlotinib | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Complete + Partial Response | 7 Participants |
| Erlotinib | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Complete Response (CR) | 1 Participants |
| Erlotinib | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Partial Response (PR) | 6 Participants |
| Erlotinib | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Stable Disease (SD) | 35 Participants |
| Erlotinib | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Progressive Disease (PD) | 36 Participants |
| Erlotinib | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Disease Control (CR+PR+SD) | 42 Participants |
| Erlotinib | Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib | Unable to Evaluate | 0 Participants |