CALGB 30303 - A PHASE II STUDY OF DOSE-DENSE DOCETAXEL AND CISPLATIN EVERY 2 WEEKS WITH PEGFILGRASTIM AND DARBEPOETIN ALPHA WITH AND WITHOUT THE CHEMOPROTECTOR BNP 7787 IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER
UTSW IRB# 072005-006  
Principal Investigator: Jonathan Dowell, MD 
Coordinator:   Candice Price, RN
Contact Number: (214) 648-5536

OBJECTIVES:  To compare the incidence and severity of peripheral neuropathy from dose-dense docetaxel and cisplatin with and without BNP 7787; to determine the response rate from dose-dense docetaxel and cisplatin with and without BNP 7787; to assess the feasibility of administering dose-dense docetaxel and cisplatin, with and without BNP 7787, in patients with advanced IIIB and IV non-small cell lung cancer.
Number of Participants:  Nationally: 152 -– Local: 5

KEY INCLUSION CRITERIA:

• Histologically or Cytologically documented non-small cell lung cancer (the following diagnostic categories are acceptable: squamous carcinoma, basaloid carcinoma, adenocarcinoma, bronchioloaveolar carcinoma, adenosquamous carcinoma, large cell carcinoma, large cell neuroendocrine carcinoma, giant cell carcinoma, sarcomatoid carcinoma, and non-small cell carcinoma NOS
• Advanced disease (Stage IIIB or IV)
• No prior chemotherapy
• Prior RT allowed for CNS mets only; CNS mets must be under control (patient neurologically stable and off steroids)
• Measurable disease
• ECOG performance status 0-1
• Age > 18 years
• Non-pregnant and non-nursing
• No patients with > grade 2 neuropathy
• Patients must have following laboratory parameters:
  • Granulocytes    ³1,500/ml
  • Platelets   ³100,000/ ml
  • Creatinine    <ULN
  • Bilirubin   <1.5 mg/dl
  • SGOT (AST)   <1.5 X ULN
  • Alkaline Phosphatase   <2.5 X ULN

KEY EXCLUSION CRITERIA:

• Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus; patients with childbearing potential must practice appropriate contraception
• Patients with > grade 2 neuropathy
  
  

  CALGB 30303 – A phase II study of dose-dense Docetaxel and Cisplatin every 2 weeks with Pegfilgrastim and Darbepoetin Alpha with and without the chemoprotector BNP7787 in patients with advanced non-small cell lung cancer
  SCHEMA
  R A N D O M I Z E	EITHER Docetaxel 75 mg/m2 IV over 1 hour on day 1 immediately followed by Cisplatin 75 mg/m2 IV over 1 hour on day 1 with adequate hydration, Darbepoetin alfa 200 mcg SC on day 1 if Hb <11g/dl, and Pegfilgrastim 6 mg SC on day 2, every 2 weeks OR Docetaxel 75 mg/m2 IV over 1 hour on day 1 immediately followed by BNP7787 40 g IV over 30 minutes on day 1 immediately followed by Cisplatin 75 mg/m2 IV over 1 hour on day 1 with adequate hydration, Darbepoetin alfa 200 mcg SC on day 1 if Hb <11g/dl, and Pegfilgrastim 6 mg SC on day 2, every 2 weeks
  The assigned therapy is repeated q2wks (2wks = 1 cycle) for 6 cycles unless the patient has intolerable toxicity or shows evidence of PD.  Hydration: “Adequate hydration” is considered at least one liter of normal saline i.v. b/f and after cisplatin in Arm I and b/f BNP7787 and after cisplatin in Arm II.  In Arm II, it is essential that pts are evaluated for their ability to maintain adequate fluid intake and for their volume status prior to each treatment cycle.  This should include any signs or symptoms of dehydration (dry mucous membranes, reduced skin turgor, orthostatic symptoms or blood pressure findings). Premedication on both arms will consist of ondansetron, granisetron, or dolasetron as antiemetic, and dexamethasone 8mg PO-BID for at least 3 days starting the day b/f therapy.  The use of aprepitant (substance P inhibitor/neurokinin 1 receptor antagonist) is allowed. Prophylactic fluconazole and ciprofloxacin or similar antibiotics, according to institutional guidelines, may be used as per physician discretion but should be noted on the remarks addenda.

RADIATION THERAPY FOLLOWED BY CONSOLIDATION ALIMTA/GEMCITABINE FOR PATIENTS WITH FAVORABLE PROGNOSIS INOPERABLE STAGE IIIA/B NON-SMALL CELL LUNG CANCER (NSCLC)
UTSW IRB# 082005-020
Principal Investigator: Hak Choy, MD
Coordinator:   Allison Rodarte
Contact Number: (214) 648-5536

OBJECTIVES:  The primary objective of this study is to determine the maximum tolerated dose and the recommended dose of pemetrexed combined with either carboplatin or cisplatin given simultaneously with curative radiotherapy, followed by pemetrexed and gemcitabine in patients with primary non-resectable stage IIIA or IIIB non-small cell lung cancer. Number of Participants:  15  Locally

KEY INCLUSION CRITERIA:

• Patients with unresected loco-regionally advanced non-small cell lung cancer without evidence of hematogenous metastases, Stages IIIA, or IIIB (without pleural effusion).   This diagnosis must be either cytological or histopathological.
• Patients must have measurable disease on the planning CT per recist criteria
• ECOG performance status 0-1
• Weight loss < 10% in three months prior to diagnosis
• FEV 1> 1000 cc
• No pleural effusion on CXR unless it appeared only after a thoracotomy or other invasive thoracic procedure was attempted
• Hemoglobin > 8.0 mg%, absolute neutrophil count > 1,5000/m3, platelets > 100,000/m3
• Renal: calculated creatinine clearance > 45 mls/min
• Serum bilirubin < 1.5 mg/dl; aspartate transaminase(AST), alanine transaminase(ALT), and alkaline phosphatase (AP)  must be < 3 times the institutional upper limits of normal unless the abnormality is caused by documented benign disease, in which case it can be < 5 times upper limit of normal
• Male or female at least 18 years old
• Patient must sign a study-specific consent form prior to registration
• Females of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopausal) must test negative for pregnancy at the time of enrollment based on a urine pregnancy test.  Both males and females of reproductive potential must agree to use a reliable method of birth control, as determined by the patient and their health care team, during the study and for 3 months following the last dose of study drug
• Spanish speaking subjects will be eligible to participate in this study.

KEY EXCLUSION CRITERIA:

• Have received treatments within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
• Have previously completed or withdrawn from this study or any other study investigating pemetrexed
• Evidence of small cell histology; Stage I, II or stage IV non-small cell cancer
• Patients who have undergone complete (or subtotal) tumor resection
• Patients with post-resection intrathoracic tumor recurrence
• Patients with a synchronous primary cancer that, in the opinion of the investigator, will impact their 2-year survival
• Patients with prior chemotherapy or thoracic or neck radiotherapy for any condition
• Patients with myocardial infarction within the preceding six months or symptomatic heart disease, including angina, congestive heart failure, uncontrolled arrhythmia
• Pregnant women are ineligible as the treatment involves unforeseeable risks to the participant and to the embryo or fetus
• Active infection  (at the discretion of the investigator)
• Breast-feeding
• Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
• Inability to discontinue administration of aspirin or other nonsteroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of PEMETREXED (5 days prior for long-acting agents such as piroxicam)
• Any pleural effusion on CXR or other clinically significant effusions, which are unable to be drained
• Planning target volume (PTV) >3 liters
• V20 >40% (>40% of existing healthy lung volume [total lung volume minus PTV] is likely to receive >20 Gy radiation)
• Patients who are unable or unwilling to comply with vitamin supplementation utilizing folic acid or vitamin B12
• Patients who are unable, due to geographic proximity or compliance concerns, accomplish the required tests and procedures for monitoring and follow-up included in this trial.

Alimta-A Phase I/II Study of Alimta, Carboplatin or Alimta, Cisplatin And Radiation Therapy Followed by Consolidation Alimta/Gemcitabine For Patients With Favorable Prognosis Inoperable Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)
SCHEMA - For Phase I
Concurrent RT with Chemo 1.8 – 2 Gy per day Days 1-49 for total dose of 63 Gy
Arm A Pemetrexed Days 1, 22, 43 Carboplatin Days 1,8,22,29, 43 Dose Level 1A 6 pts <2 DLTs ↓ Dose Level 2A 6 pts < 2 DLTs ↓ Dose Level 3A 6 pts < 2 DLTs	Arm B Pemetrexed Days 1, 22, 43 Cisplatin Days 1,8,22,29,43 Dose Level 1B 6 pts <2 DLTs ↓ Dose Level 2B 6 pts <2 DLTs ↓ Dose Level 3B 6 pts <2 DLTs
↓	↓
Consolidation to begin 3 wks after RT Biweekly Pemetrexed Plus Gemcitabine Days 1, 15, 29, 43

RTOG L-0214 - A PHASE III COMPARISON OF PROPHYLACTIC CRANIAL IRRADIATION VERSUS OBSERVATION IN PATIENTS WITH LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER
UTSW IRB# 052004-007
Principal Investigator: Robert Timmerman, MD 
Coordinator:   Allison Rodarte
Contact Number: (214) 648-5536

OBJECTIVES:  In fifty percent of patients with locally advanced non-small cell lung cancer, the cancer will spread to the central nervous system (brain) at some time during the course of their disease. The usual treatment for patients who have had effective treatment for locally advanced non-small cell lung cancer is observation or monitoring of your health. 
The purpose of this study is to compare the effects (good and bad) of brain irradiation with the standard treatment of observation to see if brain irradiation results in patients living longer. The study will also evaluate whether there is a lower risk of tumor in the brain with the use of radiation. In addition, the study will evaluate the effects of brain irradiation on the thinking skills and quality of life of those patients who receive it.
This research is being done because we do not know whether or not brain irradiation helps patients with non-small cell lung cancer live longer. We also do not know if brain irradiation is safe or if it prevents growth of small tumor deposits which already may be in the brain of patients with non-small cell lung cancer.
Number of Participants:   National: 1055  --  Local: 10

KEY INCLUSION CRITERIA:

• Patients with newly diagnosed Stage IIIA or IIIB non-small cell lung cancer having completed definitive loco regional therapy (with surgery and and/or radiation therapy, with or without chemotherapy) [chemotherapy alone does not constitute definitive therapy], with complete response, partial response, or stable disease after therapy
• Patients must be > 18 years of age
• Patients will be restaged and enrolled within 16 weeks of completing previous therapy; any acute/subacute > grade 3 toxicities from previous therapy must be resolved to < grade 2 at the time of study entry
• MRI or CT of the head showing no suspicion for CNS metastases within 6 weeks of study entry
• Patients must sign a study-specific informed consent prior to study entry

KEY EXCLUSION CRITERIA:

• Evidence of progressive disease at the time of study entry
• Evidence of extracranial distant metastatic disease
• Prior cranial irradiation
• Patients may not be entered on other phase III studies that have progression free, disease free or overall survival as a primary endpoint
• Patients with synchronous or prior malignancy, other than non-melanomatous skin cancer unless disease free greater than 3 years
• Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus; patients with childbearing potential must practice appropriate contraception

VICC THO 0319 - A PHASE II STUDY OF CONCURRENT CHEMORADIOTHERAPY WITH WEEKLY DOCETAXEL, CARBOPLATIN AND RADIATION THERAPY FOLLOWED BY CONSOLIDATION CHEMOTHERAPY WITH DOCETAXEL AND CARBOPLATIN FOR LOCALLY ADVANCED INOPERABLE NON-SMALL CELL LUNG CANCER
UTSW IRB# 042004-013  
Principal Investigator:  Hak Choy, MD
Coordinator:   Jennifer Sheppard
Contact Number: (214) 648-5536

OBJECTIVES: The standard treatment for locally advanced inoperable non-small cell lung cancer (NSCLC) is radiation therapy (treatment of tumors by way of high-dose x-ray beams) given either by itself or in combination with chemotherapy (anti-cancer drugs).   Radiation therapy given alone can control some tumor-related symptoms; however, its use for long-term survival needs improvement.  Recent studies have shown that when combining chemotherapy with radiation therapy, the tumor cells become more sensitive to the killing effects of radiation therapy.   If you decide to participate in this trial, you will receive radiation plus   the chemotherapy drugs called docetaxel and carboplatin.  Both of these drugs are FDA-approved for the treatment of NSCLC.
The purposes of this research are to: 1) see if combined chemotherapy (anti-cancer drugs) using docetaxel and radiation therapy will enhance the effects that radiation has on lung cancer; 2) determine if this combination of treatments will be more effective than the current treatments used to control tumor growth, and 3) evaluate the side effects of this combined treatment using docetaxel plus carboplatin and radiation therapy.
Number of Participants:   National:   90  --  Local:  5-10

KEY INCLUSION CRITERIA:

• Non-metastatic, inoperable, Stage IIIA or IIIB histologically or cytologically documented NSCLC without evidence of malignant pleural effusion
• No prior systemic chemotherapy, thoracic radiotherapy or surgical resection for treatment of NSCLC
• Must have at least one site of unidirectionally measurable disease
• Must be greater than 3 weeks from a formal exploratory thoracotomy
• Must have a Radiation Oncology and Medical Oncology consult and approval prior to study entry
• Patient must be over 18 years old
• Must have an ECOG performance status of 0 or 1
• Women of childbearing potential must have a negative baseline serum pregnancy within 7 days prior to Week 1, Day 1 and must not be breast-feeding
• Women of childbearing potential and men with a sexual partner of childbearing potential must use an effective method of contraception beginning prior to study entry, for the duration of the study participation and for a minimum of 3 months after the last dose of chemotherapy.
• Patients must have adequate hepatic, renal, lung, and bone marrow function as defined as:
  • Absolute neutrophil count (ANC) of  > 1,500/mm³
  • Hemoglobin > 9.0 gm/dL
  • Platelets > 100,000/mm³
  • Total Bilirubin within normal limits (WNL)
  • AST or ALT and Alkaline Phosphatase must be within the range allowing for eligibility, as in the table below:

• Creatinine Clearance > 50 ml/min. (calculated via Cockroft-Gault  formula)
• FEV1 > 800cc

KEY EXCLUSION CRITERIA:

• Known hypersensitivity to drugs formulated with polysorbate 80
• Peripheral neuropathy Grade ≥ 2
• Wet stage IIIB (documented malignant pleural effusion) or stage IV NSCLC
• Previous chemotherapy or radiation therapy
• Any concomitant malignancy, brain metastasis or uncontrolled, clinically significant medical or psychiatric disorder
• Pregnant or nursing women
• A greater than or equal to 10% weight loss over the past 3 months

SCHEMA
Concurrent Chemoradiotherapy (Weeks 1-7):

¹    D = Docetaxel  (20 mg/m²/wk) IV over 30 minutes once/week x 7 weeks
Premedication:   dexamethasone 4 mg orally, beginning 12 hours prior to docetaxel infusion, 1 hour prior to docetaxel infusion and 12 hours after docetaxel infusion for a total of 3 doses
²C = Carboplatin (AUC 2) IV over 30 minutes following docetaxel, once/ week x 7 weeks
³   RT = 1.8 Gy per day x 5 days per week during Weeks 1-5 ; Total Dose = 45 Gy
⁴    RT = 2.0 Gy per day x 5 days during Week 6 and x 4 days during Week 7; Total Dose = 18 Gy
(21 day rest – Weeks 8-10) Includes Post-Evaluation with Staging Work-Up during Weeks 9 or 10

Stable Disease, PR and CR                            
Progressive Disease (Discontinue Treatment)
Consolidation Chemotherapy (Weeks 1-6):

D ⁵= Docetaxel  (75 mg/m²) IV over 60 minutes once/ 3 weeks x 2 cycles
Premedication:   dexamethasone 8 mg orally, beginning 12 hours prior to docetaxel infusion, and continuing q 12 hours for a total of 5 doses
Antiemetic:   5HT₃ (dolasetron, granisetron, ondansetron) agent of choice IV or orally within 60 minutes prior to consolidation chemotherapy infusion
C ⁶ = Carboplatin (AUC 6) IV over 30 minutes following docetaxel, once/ 3 weeks x 2 cycles

RTOG 0212 - A PHASE II/III RANDOMIZED TRIAL OF TWO DOSES (PHASE III-STANDARD VS. HIGH) AND TWO HIGH DOSE SCHEDULES (PHASE II-ONCE VS. TWICE DAILY) FOR DELIVERING PROPHYLACTIC CRANIAL IRRADIATION FOR PATIENTS WITH LIMITED DISEASE SMALL CELL LUNG CANCER
UTSW IRB# 052004-017 
Principal Investigator: Robert Timmerman, MD
Coordinator:   Carolyn Zwartjes
Contact Number: (214) 648-5536

OBJECTIVES:  In fifty percent of patients with small cell lung cancer, the cancer will spread to the central nervous system at some time during the course of their disease. The purpose of this study is to compare the effectiveness of standard dose and high dose brain irradiation in preventing small cell lung cancer from spreading to the brain. In addition, the study will compare the effectiveness of two schedules of high dose brain irradiation in preventing lung cancer from spreading to the brain.
The purpose of this study is to compare the effects (good and bad) of brain irradiation doses to see which brain irradiation dose results in patients living longer, the standard dose or the studied dose. The study will also evaluate whether there is a lower risk of tumor in the brain with the use of radiation. In addition, the study will evaluate the effects of brain irradiation on the thinking skills and quality of life of those patients who receive it. Depending on which schedule of treatment the patient receives, the patient will receive brain irradiation for either 2-3 or 3-4 weeks. Follow-up visits, including completion of tests to evaluate memory and thinking abilities and 2 questionnaires about quality of life, will continue for 3 years.
Number of Participants: National: 264 --  Local: 10

KEY INCLUSION CRITERIA:
1) Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy, or two positive sputa) of SCLC;
2) Patients must have limited disease SCLC after clinical staging evaluation (See Appendix III): clinical TNM stages I-IIIB (i.e., confined to one hemithorax, but excluding T4 tumor based on malignant pleural effusion and N3 disease based on contralateral hilar or contralateral supraclavicular involvement);
3) Patients must have completed all of their prescribed chemotherapy at least one week prior to study entry; the plan for PCI should be such that PCI begins no more than 240 days from the start of induction chemotherapy;
4) Patients must have achieved a complete response to induction chemotherapy (+/- thoracic radiation therapy) assessed according to local habits (at least on a chest x-ray) at the time of study entry;
5) Patients may have started consolidative chest irradiation by the time of study entry;
6) Zubrod performance status ≤ 1. Patient must be fully active or restricted in physically strenuous activity but able to light work (e.g. light housework, office work);
7) Normal brain CT scan or MRI < 1 month prior to study entry;
8) Neurological function class of 1 or 2;
9) HGB level of 10.0 gm/100 ml, an absolute granulocyte count of ≥ 1,500/µl, and a platelet count of ≥ 75,000/µl are required;
10) Patients of childbearing potential (male or female) must practice adequate contraception due to possible harmful effects of radiation and chemotherapy on an unborn child;
11) A "certified" test administrator (Section 11.4) is required for administration of the neuropsychological tests;
12) Long-term follow up must be possible;
13) Patients must sign a study-specific informed consent prior to study entry.

KEY EXCLUSION CRITERIA:
1) Patients receiving prior external beam irradiation to the head or neck, including any form of stereotactic irradiation;
2) Radiographic evidence of brain metastases and/or ipsilateral lung metastases/malignant pleural effusion;
3) Concomitant malignancy or malignancy within the past five years other than nonmelanomatous skin cancer or carcinoma in situ of the cervix;
4) Patients with minimal pleural effusion evident on CXR; minimal pleural effusion visible on chest CT is allowed;
5) Patients must not have a serious medical or psychiatric illness that would, in the opinion of the investigator, prevent informed consent or completion of protocol treatment, and/or follow-up visits.

RTOG 0236 - A PHASE II TRIAL OF STEREOTACTIC BODY RADIATION THERAPY (SBRT) IN THE TREATMENT OF PATIENTS WITH MEDICALLY INOPERABLE STATE I/II NON-SMALL CELL LUNG CANCER
UTSW IRB# 092004-023
Principal Investigator: Robert Timmerman, MD 
Coordinator:   Jennifer Sheppard
Contact Number: (214) 648-5536

OBJECTIVES: The usual treatment for early stage lung cancer is to remove the cancer with surgery. However, when patients have other serious health problems like emphysema, diabetes, or heart disease, they may not be able to have the standard surgery. Patients who cannot have surgery can receive radiation therapy. Standard radiation therapy involves several weeks of daily treatment sessions. While this therapy is sometimes successful at killing the cancer, it is not as effective as surgery and may seriously damage normal surrounding lung tissue. A newer treatment technique using radiation therapy, stereotactic body radiation therapy (SBRT), has been developed and used for patients with metastases to the lungs. Metastases are cancerous tumors that have spread from one organ to another. This newer treatment gives fewer but higher doses of radiation than standard radiation. It uses special equipment to position the patient and guide focused beams toward the cancer and away from normal surrounding lung tissue. The higher dose technique may work better to kill cancer cells with fewer side effects than standard radiation therapy.

The purpose of this study is to use SBRT with patients with early stage lung cancer and find out what effects (good and bad) SBRT has on you and your cancer. This research is being done because SBRT has not been used very often in patients with early stage lung cancer or in patients with other serious health problems. In addition, this study also will gather information about your health and hospitalization history. This information will be used to find out if there are factors that can predict recovery or outcome of patients with lung cancer.
Number of participants: National: 52 -- Local: 5

KEY INCLUSION CRITERIA:
1) Histologic confirmation of non-small cell cancer by biopsy or cytology;
2) AJCC Stage I or II: T1N0M0; T2 (≤5cm), N0M0; T3 (≤5cm), N0M0 chest wall primary tumors only;
3) Hilar or mediastinal lymph nodes ≤1cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Patient with ≥1cm hilar or mediastinal lymph nodes on CT or abnormal PET are eligible if tissue biopsy of all abnormally identified areas are negative for Ca;
4) Primary tumor must be deemed technically resectable with reasonable possibility of obtaining a gross total resection with negative margins (potentially curative resection PCR). However, the patient should have underlying physiological medical problems that would prohibit a PCR due to low probability of tolerating the procedure, therefore "medically inoperable";
5) Patients ≥18 years of age;
6) Zubrod 0-2. This is a measurement of how active you are. You must be able to walk and take care of yourself. You must be up and about more than 50% of waking hours;
7) Women of childbearing potential and male participants must use effective contraception;
8) Patients must sign study-specific consent.

KEY EXCLUSION CRITERIA:
1) Patients with T2 or T3 primary tumors >5cm or patients with T3 primary tumors involving the central chest and structures of the mediastinum;
2) Primary tumor of any T-stage within or touching the zone of the proximal bronchial tree defined as a volume 2 cm in all directions around the bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi;
3) Evidence of regional or distant metastases;
4) Patients who refuse a PCR due to preference, ideology, emotional or psychological issues, mental illness or inability to give consent;
5) Previous lung or mediastinal radiotherapy;
6) Plans to receive other concomitant antineoplastic therapy including: standard radiotherapy, chemotherapy, biological therapy, vaccine therapy, and surgery while on this protocol except at disease progression;
7) Patients with active systemic, pulmonary or pericardial infection;
8) Pregnant or lactating women.

JM 216 - A PHASE I/II STUDY WITH SATRAPLATIN AND SIMULTANEOUS RADIATION IN NON-SMALL CELL LUNG CANCER
UTSW IRB# 082004-013
Principal Investigator: Hak Choy, MD
Coordinator:  Jennifer Sheppard
Contact Number: (214) 648-5536

OBJECTIVES: Patients who have been diagnosed with non-small cell lung cancer that is to be treated with radiation therapy will be offered inclusion in this study. Sometimes chemotherapy helps the radiation to be more effective. The purpose of this study is to find out the highest dose of the experimental drug, satraplatin that can be given in combination with radiation without causing severe side effects.
Satraplatin is a new experimental oral drug containing platinum. Currently available platinum containing drugs are only available as an injection. Platinum is a heavy metal that has anti-cancer properties, and drugs containing platinum have been in use for a variety of cancer treatments for over 25 years. Satraplatin has been taken by over 600 people in different clinical trials, although it remains experimental.
This research is being done because, although the use of other platinum drugs in combination with radiation has shown some improvement in response to treatment, and may result in improvement in long-term outcome, currently there is no truly effective treatment for this type of cancer. Satraplatin is the only platinum drug that can be taken by mouth. This should make it easier to take than an intravenous platinum drug during the course of radiation therapy. Number of Participants: 24 -30 participants (UTSW study only)

KEY INCLUSION CRITERIA:
1. Patients with pathologic diagnosis of locally advanced NSCLC, medically inoperable (stage II/II), who are to receive radiation therapy to primary disease site;
2. Males or females age 18 or older;
3. ECOG performance status score 0-2. Patients must be fully active or restricted in physically strenuous activity but able to do light work (e.g. light housework, office work);
4. Life expectancy of at least three months;
5. Adequate bone marrow function: absolute neutrophil count (neutrophils and bands) > 2 x 109/L; platelet count > 100 x 109/L;
6. Adequate liver function: total bilirubin < 1.5 mg/dl; alanine aminotransferase <1.25 x upper normal limit* (UNL) alkaline phosphatase < 1.25 x UNL (except when secondary to malignancy but within CTTCAE grade 1, i.e. < 2.5 x UNL);
7. Adequate renal function: serum creatinine within institutional normal range; or creatinine clearance defined as measured creatinine clearance greater than 60 ml/min or institutional lower limit, whichever is less. (Creatinine clearance is required only if serum creatinine is elevated);
8. Adequate pulmonary function: FEV1> 1.2 L;
9. Patients must be able to swallow pills;
10. Patients must be willing and able to give written informed consent prior to study.

KEY EXCLUSION CRITERIA:
1. History of prior malignancy except appropriately treated in situ carcinoma of the cervix or localized epithelial skin cancer. Patients with historically remote malignancies of other types may be entered after consultation with an approval by the sponsor;
2. Patients who have a serious concurrent uncontrolled medical disorder;
3. Patients with uncontrolled or significant cardiovascular disease, including a recent (< 6 months) myocardial infarction, any degree of congestive heart failure with or without medical treatment, any history of clinically significant atrial or ventricular arrhythmias;
4. Patients with a history of gastrectomy;
5. Pregnant or breast feeding patients are not eligible. Fertile patients must use effective birth control. All women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L of -HCG) within 72 hours prior to the start of study medication;
6. Patients who have had prior radiotherapy to the primary tumor site or have received cytotoxic chemotherapy
Note: All lab studies will be done no more than two weeks before therapy is begun, pregnancy test within 72 hours of the first course.

SCHEMA
The starting dose and schedule of satraplatin will be 10 mg/day given five times weekly for seven weeks in combination with radiotherapy. After completion of the radiation therapy, patients will receive consolidation therapy consisting of docetaxel 75 mg/m2 IV every 21 days for 3 cycles. Consolidation will begin no sooner than 3 weeks, and no more than 6 weeks after completion of radiation.

Dose Escalation:  The proposed dose escalation is as follows:

<sup>* If dose level 5 is reached, and there has been minimal or no toxicity, higher dose levels will be investigated, and the protocol will be amended. The next cohort will be open depending on the observed toxicities at the previous cohort, as follows:
- At dose levels with no or minimal toxicity, three patients will be treated;
- Additional patients (nominally up to six) will be entered at a given dose level if any DLT (see Section 10.5 for definition of DLT) is observed, or if two or more patients have toxicity close to DLT;
- If no more than two-sixth patients (two of six, or less) meet DLT criteria dose escalation will continue.

The MTD will be defined as that dose of drug which causes DLT in more than two patients. Additional patients may be entered as needed at any dose level to better characterize the pattern of toxicity and/or better define the recommended Phase II dose.
At least three patients will be evaluated for a minimum of three weeks after satraplatin administration, or recovery to < grade I toxicity (whichever is longer, and excluding alopecia from consideration), at each dose level prior to any dose escalation in subsequent cohorts of patients.</sup>

Consolidation Chemotherapy
^{All patients, following completion of the seven week course of chemoradiation, will receive three additional cycles of chemotherapy with docetaxel. Consolidation will begin no sooner than 3 weeks and no more than 6 weeks after completion of radiation.}

Docetaxel Schedule

^{*Cycle = 21 days}

Pending Closure: RTOG 0241 - PHASE I STUDY OF IRINOTECAN AND CISPLATIN IN COMBINATION WITH TWICE DAILY THORACIC RADIOTHERAPY (45 Gy) OR ONCE DAILY THORACIC RADIOTHERAPY (70 Gy) FOR PATIENTS WITH LIMITED STAGE SMALL CELL LUNG CANCER
UTSW IRB# 082004-059
Principal Investigator: Robert Timmerman, MD
Coordinator:   Candice Price, RN
Contact Number: (214) 648-5536

OBJECTIVES: The standard treatment for Limited Stage Small Cell Lung Cancer (SCLC) is a combination of chemotherapy and radiation. The purpose of this study is to find out what effects (good and bad) the drug, irinotecan, given in combination with chemotherapy (cisplatin) and radiation, has on patients with limited SCLC. While irinotecan is one type of standard therapy for lung cancer, it is considered by most experts to be investigational when given during radiation. This study will find out the highest dose of irinotecan that can be safely given with chemotherapy and radiation. Groups of patients will receive irinotecan in increasing doses between 40-60 mg until at least some of the patients experience severe side effects.
This research is being done because irinotecan plus cisplatin has been shown to be more effective than other chemotherapy in a type of cancer called extensive small cell lung cancer. However, the safety of irinotecan has not yet been studied in treatment of limited SCLC. Adding irinotecan to chemotherapy and radiation might make these treatments more effective. However, adding irinotecan also could result in a serious increase in side effects. Number of Participants:  National: 36 and Local: 10

KEY INCLUSION CRITERIA:
1. Histologic or unequivocal cytologic proof (fine needle aspiration biopsy or two positive sputa) of SCLC is required;
2. Patients must have limited disease, clinical stage I-IIIB: confined to one hemithorax, but excluding T4 tumor based on malignant pleural effusion and N3 disease based on contralateral hilar or contralateral supraclavicular involvement;
3. Patients with minimal pleural effusion too small to tap under CT guidance, and not evident on CXR, are eligible;
4. Pretreatment FEV-1 ≥ 1.0 L/sec;
5. Patients must have measurable or evaluable disease;
6. Age ≥ 18;
7. Zubrod Performance Score 0-1. Patients must be fully active or restricted in physically strenuous activity but able to do light work (e.g. light housework, office work).

KEY EXCLUSION CRITERIA:
1. T4 tumor based on malignant pleural or pericardial effusion and N3 disease based on contralateral hilar or contralateral supraclavicular involvement;
2. Patients with complete tumor resection;
3. Prior chemotherapy, radiotherapy, or biotherapy;
4. Pre-existing ≥ grade 2 peripheral neuropathy;
5. Pericardial effusion (regardless of cytology);
6. Serious intercurrent medical illness including symptomatic heart disease, myocardial infarction within 6 months, uncompensated COPD, or uncontrolled bronchospasm;
7. Previous or concurrent malignancy other than curatively-treated basal or squamous cell skin cancer or carcinoma in situ (e.g., TIS of bladder or cervix); patients managed for a nonpulmonary invasive malignancy more than 2 years previously with no subsequent clinical, laboratory, imaging, or pathologic evidence of recurrence or persistence of the prior malignancy are eligible for this protocol;
8. Pregnant or lactating women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus;
9. Patients with known Gilberts disease;
10. Patients who have been receiving phenytoin, phenobarbital, carbamazepine or any other enzyme-inducing anti-convulsant drug (EIACD) on a regular basis for > 2 weeks who are unable or unwilling to discontinue EIACD use or switch to a non-EIACD at least 7 days prior to first treatment dose of irinotecan. Patients who have been receiving EIACDs < 2 weeks must discontinue use prior to first treatment dose on study but do not require a 7-day wash-out period. Concomitant use of gabapentin or other non-EIACDs is permitted;
11. Patients who are unable or unwilling to discontinue St. John’s Wort.

Pending: RTOG 0015 - A RANDOMIZED PHASE III TRIAL OF SURGERY ALONE OR SURGERY PLUS PREOPERATIVE PACLITAXEL/CARBOPLATIN IN CLINICAL STAGE IB (T2N0), II (TI-2N1, T3N0) AND SELECTED IIIA (T3N1) NON-SMALL CELL LUNG CANCER
UTSW IRB# - Pending