Please select the eligibility criteria that correspond to the clinical trial below.
Title: A British Thoracic Oncology Group Phase III Trial of Gemcitabine Plus Cisplatin at 80mg/m Versus Gemcitabine Plus Carboplatin At 50 mg/m Versus Gemcitabine Plus Carboplatin AUC 6 in Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC)
Brief Summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether giving gemcitabine together with cisplatin is more effective than giving gemcitabine together with carboplatin in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying gemcitabine and cisplatin to see how well they work compared to gemcitabine and carboplatin in treating patients with stage III or stage IV non-small cell lung cancer.


Options:
A: Inclusion Criteria:

* Confirmed NSCLC
* Stage IV disease at the time of study entry
* Measurable disease at the time of study entry
* Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (except alopecia)
* Adequate hematologic function, hepatic function, renal function and coagulation function
* If sexually active, must be post-menopausal, surgically sterile, or using effective contraception; and agrees to use adequate contraception during the study period and for up to 6 months after the last dose of study medication
* Female participants of childbearing potential must have a negative serum pregnancy test

Exclusion Criteria:

* Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
* Tumor wholly or partially contains small cell lung cancer
* Untreated central nervous system (CNS) metastases, eligible if they are clinically stable with regard to neurologic function, off all steroids after cranial irradiation at least 2 weeks prior or after surgical resection performed at least 4 weeks prior to randomization
* Concurrent active malignancy other than adequately treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years
* Received prior therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR)
* Receiving concurrent treatment with other anticancer therapy
* Has received previous chemotherapy for Stage IV NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 6 months prior to randomization)
* Has radiologically documented evidence of major blood vessel invasion or encasement by cancer
* Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions)
* Ongoing or active infection
* History of significant neurological or psychiatric disorders
* Experienced clinically relevant coronary artery disease, myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, or symptomatic poorly controlled arrhythmia
* Poorly-controlled hypertension
* Experienced any serious Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry
* Receiving chronic daily treatment with aspirin (\> 325 mg/day) or other known inhibitors of platelet function
* Serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
* Major surgery within 28 days prior the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to randomization
* Elective or a planned major surgery
* Pregnant or lactating
* Any other serious uncontrolled medical disorders or psychological conditions
* Allergy / history of hypersensitivity reaction to any of the treatment components
* History of drug abuse
B: Inclusion Criteria:

* Men \& women ≥18 years of age
* Subjects with histologically or cytologically-documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease) and who will receive study therapy as second or third line of treatment for advanced disease
* Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
* Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient

Exclusion Criteria:

* Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10mg daily prednisone (or equivalent)
* Subjects with carcinomatous meningitis
* Subjects with active or recent history of known or suspected autoimmune disease. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll
* Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
* Prior therapy with anti-programmed death-1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
* Prior treatment with Docetaxel
* Treatment with any investigational agent within 14 days of first administration of study treatment

Other protocol-defined inclusion/exclusion criteria apply
C: DISEASE CHARACTERISTICS:

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

  * Stage IIIB disease\* that is not suitable for radical radiotherapy
  * Stage IV disease\* NOTE: \*Radiographically verified
* At least 1 measurable lesion by clinical examination or radiography
* No mixed histologies of small cell lung cancer and NSCLC
* No clinically apparent brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-2

Life expectancy

* At least 12 weeks

Hematopoietic

* WBC ≥ 3,000/mm³
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL

Hepatic

* AST \< 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* Alkaline phosphatase \< 3 times ULN
* Bilirubin \< 1.5 times ULN

Renal

* Creatinine clearance ≥ 60 mL/min (by Wright equation) OR ≥ 70 mL/min (by \^51Cr-EDTA clearance)

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able and willing to participate in the quality of life assessment
* No pre-existing neuropathy \> grade 2
* No other malignancy that would preclude study treatment or study comparisons
* No evidence of severe or uncontrolled systemic disease, significant clinical disorder, or laboratory finding that would preclude study participation
* No psychiatric disorder that would preclude study participation
* No other condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy

Chemotherapy

* No prior chemotherapy, including neoadjuvant or adjuvant chemotherapy
* No other concurrent cytotoxic chemotherapy

Endocrine therapy

* No concurrent hormonal therapy except contraceptives or replacement steroids

Radiotherapy

* No prior radiotherapy

Surgery

* Recovered from prior surgery
* Prior surgical resection for NSCLC allowed

Other

* More than 12 weeks since prior investigational agents and recovered
* No other concurrent specific antitumor therapy
* No other concurrent investigational agents
D: Inclusion Criteria:

* Men and women ≥18 years of age
* Subjects with histologically or cytologically-documented squamous cell NSCLC who present with Stage IIIB/IV disease or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiation therapy for locally advanced disease)
* Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
* Measurable disease by computed tomography (CT)/Magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient

Exclusion Criteria:

* Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent)
* Subjects with carcinomatous meningitis
* Subjects with active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
* Prior therapy with anti-Programmed death-1 (PD-1), anti-Programmed cell death ligand 1 (PD-L1), anti-Programmed cell death ligand 2 (PD-L2), anti-CD137, or anti-Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
* Prior treatment on the first line study CA184104 first line NSCLC study
* Prior treatment with Docetaxel
* Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
* Treatment with any investigational agent within 14 days of first administration of study treatment

Answer: C