Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2 Trial of Pemetrexed and Cisplatin Followed Sequentially by Gefitinib Versus Pemetrexed and Cisplatin in Asian "Never Smoker" Patients With Advanced Non-Small Cell Lung Cancer
Brief Summary: The purpose of this study is to compare the efficacy and safety of chemotherapy followed sequentially by gefitinib versus chemotherapy alone in the first line treatment of non-small cell lung cancer (NSCLC). This study will be conducted in Asian patients who are classified as 'never smoker' since it is suggested that these patients are more likely to respond favorably to treatment with gefitinib.


Options:
A: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer meeting 1 of the following stage criteria:

  * Stage IIIB

    * Pleural fluid and/or supraclavicular nodes allowed provided patient is not eligible for consolidation radiotherapy
  * Stage IV disease
* No disease progression after 2-6 courses of prior platinum-containing first-line palliative induction chemotherapy
* Brain metastases allowed provided patients are asymptomatic after cranial irradiation completed at least 4 weeks ago

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-2

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Pulmonary

* No history, signs, or symptoms of clinically active interstitial lung disease

  * Patients with chronic, stable, asymptomatic radiographic changes are eligible

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up
* No other malignant disease within the past 5 years except basal cell skin cancer or adequately treated superficial carcinoma of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy

Chemotherapy

* See Disease Characteristics
* Recovered from prior chemotherapy (alopecia allowed)
* No concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics

Surgery

* Not specified

Other

* No prior epidermal growth factor receptor inhibitors
* No concurrent administration of any of the following drugs:

  * Phenytoin
  * Carbamazepine
  * Rifampin
  * Phenobarbital
  * Hypericum perforatum (St. John's wort)
* No other concurrent anticancer therapy
* No other concurrent experimental drugs
B: Inclusion Criteria:

* Histologically or cytologically confirmed locally advanced or metastatic (stage=IIIB/IV) non-small cell lung cancer (NSCLC) before the front line chemotherapy. Note: sputum cytology alone is not acceptable
* Patients have completed 4 cycles of first line platinum contained doublet chemotherapy without progression or intolerable toxicity.
* Patients with PR or SD on study entry need to have one or more measurable lesions according to RECIST criteria.
* The study treatment should be started at least 3 weeks (21 days) but no more than 6 weeks (42 days) since last dose of chemotherapy, and within 4 weeks (28 days) since last tumour assessment.

Exclusion Criteria:

* Prior exposure to monoclonal antibodies or small molecule inhibitors against EGFR receptors. (e.g. gefitinib, erlotinib, C225)
* Patients with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they are clinically stable and have been discontinued from steroid therapy for at least 4 weeks prior to first dose of study medication.
* Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded)
* Known biomarker status of one or more of the following: Tumour EGFR gene copy number, tumour EGFR gene mutation status, tumour EGFR protein expression.
C: Inclusion Criteria:

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;
   * hepatic;
   * renal.
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 for alopecia).
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 documented.
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 treatment period.
15. Patient compliance and geographic proximity that allow adequate follow-up.

Exclusion Criteria:

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 dementia.
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 pemetrexed.
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 dexamethasone.
D: Inclusion Criteria:

* Histologic or cytologic diagnosis non-small cell lung cancer (NSCLC) (Stage IIIB or IV)
* Have not received any prior chemotherapy, molecular therapy, immunotherapy, biological therapy, or radiotherapy. Exception: palliative radiotherapy that is completed at least 4 weeks prior to study enrolment.
* Have 'never smoked' (defined as having smoked \<100 cigarettes during his/her lifetime)
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

Exclusion Criteria:

* Concurrent administration of any other tumor therapy
* Other co-existing malignancies
* Pregnancy or breast feeding
* Serious concomitant disorders
* Inability or unwillingness to take folic acid or vitamin B12 supplementation

Answer: D