Study of Pralatrexate vs. Erlotinib for Non-Small Cell Lung Cancer After at Least 1 Prior Platinum-based Treatment
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pralatrexate; Erlotinib; Vitamin B12; Folic Acid
Intervention description: 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.; 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.; 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.; 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.
Intervention MeSH terms: Vitamins; Folic Acid; Vitamin B 12; Vitamin B Complex; Erlotinib Hydrochloride; 10-deazaaminopterin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 201.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage IIIB/IV non-small cell lung cancer; Non-small cell lung cancer; NSCLC; Lung Cancer; Pralatrexate; Erlotinib; Tarceva; PDX; Smoking; Smoker

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)
    

Eligibility criteria:

        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.