Phase 2 Randomized, Controlled, Open-label Study of Pemetrexed Versus Gefitinib in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer Who Have Previously Received Platinum-Based Chemotherapy Without EGFR Mutations
1. Informed consent must be signed.
2. At least 18 years of age.
3. Histologic or cytologic diagnosis of NSCLC.
4. Locally advanced or metastatic disease (stage IIIB, or IV) that is not amenable to
definitive surgery or radiotherapy.
5. Patients must have previously received one platinum-based chemotherapy regimen for
palliative therapy of locally advanced or metastatic disease. Patients are also
eligible if they have received one platinum-based chemotherapy regimen as neoadjuvant
or adjuvant chemotherapy and the disease recurred within six months since the
finishing of neoadjuvant or adjuvant chemotherapy.
6. Without EGFR mutations.
7. At least one measurable lesion as defined by RECIST criteria.
8. ECOG PS0 - 2.
9. Adequate organ function including the following:
- bone marrow;
10. Prior chemotherapy must be completed at least 3 weeks prior to the study enrollment,
and the patient must have recovered from the toxic effects of the treatment (except
11. Previous palliative radiation therapy is allowed, but limited in LESS 25% of the bone
marrow and must not have included whole pelvis radiation. Patients must have
recovered from the toxic effects of the treatment prior to study enrollment (except
for alopecia). Prior radiotherapy must be completed one month before study entry.
Radiotherapy should not be administered to target lesions selected for this study,
unless progression of the selected target lesions within the radiation portal is
12. Estimated life expectancy of at least 8 weeks.
13. For women:
- must be surgically sterile;
- postmenopausal; OR
- compliant with a medically approved contraceptive regimen during and for 3
months after the treatment period; must have negative serum or urine pregnancy
test and must not be lactating.
14. For men:
- must be surgically sterile; OR
- compliant with a contraceptive regimen during and for 3 months after the
15. Patient compliance and geographic proximity that allow adequate follow-up.
1. Have received treatment within the last 30 days with a drug that has not received
regulatory approval for any indication at the time of study entry or concurrent
administration of any other anti-tumor therapy.
2. Have previously participated in a study involving pemetrexed or EGFR-TKI
3. Hypersensitivity to pemetrexed or gefitinib or any ingredients in the two drugs.
4. Symptomatic central nervous system (CNS) metastases and asymptomatic CNS metastases
requiring concurrent corticosteroid therapy. Treated stable CNS metastases are
allowed; the patient must be stable after radiotherapy for more than 2 weeks and off
of corticosteroids for more than 1 week. .
5. History of another malignancy within the last 5 years except cured carcinoma in-situ
of uterine cervix, cured basal cell carcinoma of skin and superficial bladder tumors
(Ta, Tis and T1)
6. Lack of physical integrity of the upper gastrointestinal tract, or malabsorption
syndrome, or inability to take oral medication, or have active peptic ulcer disease.
7. Patients with interstitial lung disease.
8. Any unstable systemic disease (including active infection, hepatic, renal or
metabolic disease) or serious concomitant disorders that would compromise the safety
of the patient, or compromise the patient's ability to complete the study, at the
discretion of the investigator.
9. Significant cardiovascular event: congestive heart failure >NYHA class 2; unstable
angina, active CAD (myocardial infarction more than 1 year prior to study entry is
allowed); serious cardiac arrhythmia requiring antiarrythmic therapy ( beta blockers
or digoxin are permitted) or uncontrolled hypertension.
10. History of significant neurological or mental disorder, including seizures or
11. Incision from operation has not healed before the start of study treatment (Small
incision for biopsy is eligible.)
12. Pregnant or breast-feeding women and childbearing potential women with either a
positive or no pregnancy test within 48 hours of the start of treatment.
Postmenopausal women must have been amenorrhoeic for at least 12 months to be
considered of non-childbearing potential.
13. Concurrent use of St. John's Wort, Rifampicin, and/or ritonavir.
14. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
2 days before, the day of, and 2 days after the dose of pemetrexed. If a patient is
taking an NSAID (Cox-2 inhibitors included) or salicylate with a long half-life
(e.g., naproxen, piroxicam, diflunisal, nabumetone, rofecoxib, or celecoxib) it
should not be taken 5 days before, the day of, and 2 days after the dose of
15. Presence of clinically detectable (by physical exam) third-space fluid collections,
for example, ascites or pleural effusions that cannot be controlled by drainage or
other procedures prior to study entry.
16. Inability or unwillingness to take folic acid, vitamin B12 supplementation, or