Study of Arsenic Trioxide in Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to study the effect of an anticancer drug, Arsenic Trioxide, in patients with small cell lung cancer who have failed at least one standard chemotherapy regimen as well as patients who are unable to tolerate the standard treatment for their cancer. The investigators seek to establish the safety of and efficacy of Arsenic Trioxide in this patient group. The study will include up to 36 participants with small cell lung cancer. The investigators want to find out what effects, good or bad, that the study drug has on your cancer. This study will also look at specific biomarkers in your blood and in the tumor tissue which may help the investigators to determine if the levels of these biomarkers are related to tumor response to treatment. Arsenic Trioxide, also known by the brand name, Trisenox, is a chemotherapy drug approved by the Food and Drug Administration (FDA) for the treatment of a specific type of blood cancer called Acute Promyelocytic Leukemia. It works in part by making cancer cells become more mature thereby stopping them from growing in number and more likely to die off.

Official Title
-----------------
A Single Arm, Two-Stage Phase II Study of Arsenic Trioxide in Previously Treated Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer, Cancer of Lung, Pulmonary Cancer, Pulmonary Neoplasms, Carcinoma, Small Cell

Intervention / Treatment
-----------------
* Drug: Arsenic Trioxide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have histologically or cytologically confirmed small cell lung cancer Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or as > 10 mm with spiral CT scan. Patient must have failed or found to be intolerant of standard frontline platinum-based regimens. There is no limit on the number of prior regimens provided the patient meets all the other eligibility criteria. Adult patients 18 years or older. Because no dosing or adverse event data are currently available on the use of arsenic trioxide in patients < 18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable. Life expectancy of greater than 3 months Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2 Patients must have normal organ and marrow function as defined below: absolute neutrophil count > 1,500/mL platelets > 100,000/mL total bilirubin ≤ 1.5 X institutional upper limits of normal aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 X institutional upper limit of normal creatinine ≤ 1.5 X institutional upper limits of normal OR creatinine clearance > 40 mL/min/1.73 m² for patients with creatinine levels above institutional normal. Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential Ability to understand and the willingness to sign a written informed consent document. No history of QTc prolongation syndrome or any other cardiac conduction abnormality evidenced by normal baseline EKG (QTc ≤ 450 in males and ≤ 470 in females) Both men and women and members of all races and ethnic groups are eligible for this trial. Exclusion Criteria: Need for treatment with chemotherapy (within 4 weeks; 6 weeks for nitrosoureas or mitomycin C); radiotherapy or biologic agents (within 2 weeks) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients may not be receiving any other investigational agents. Patients with uncontrolled symptomatic brain metastases. Patients with no known brain metastasis are not required to undergo screening prior to enrolment. History of allergic reactions attributed to compounds of similar chemical or biologic composition to arsenic trioxide. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded from this study because Trisenox is a category D agent with the potential to cause fetal harm. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Trisenox, breastfeeding should be discontinued if the mother is treated with Trisenox. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Trisenox. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. Patients who require ongoing treatment with any hematopoietic colony-stimulating growth factors (e.g., granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) ≤ 2 weeks prior to starting study drug. Patients who are currently receiving treatment with medication that has the potential to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy History of another malignancy within 3 years, except curatively treated basal cell carcinoma of the skin, ductal carcinoma in situ (DCIS), early stage prostate cancer without detectable prostate-specific antigen (PSA) or excised carcinoma in situ of the cervix Patient is unable or unwilling to abide by the study protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arsenic Trioxide Treatment<br>This is a single arm study. All patients will be treated with the investigational agent, Arsenic Trioxide, according to the dose and schedule indicated in the protocol. | Drug: Arsenic Trioxide<br>* Drug will be given as a loading dose of 0.32mg/kg/day for 4 days in Week 1, followed by 0.25mg/kg/day twice per week for 5 weeks, followed by 2 weeks of rest, at which time response assessment will be performed. Patients will be restaged prior to the beginning of a new cycle, every 2 months on average. Maximum of 6 cycles of therapy will be administered in the absence of tumor progression or excessive side effects<br>* Other names: ATO;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (RR) | Response rate (complete response [CR]+ partial response [PR]) was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Every 8 weeks | 
| Clinical Benefit Rate (CBR) | Sum of complete response (CR), partial response (PR) and stable disease (SD) in patients eligible for efficacy analysis. | After completing at least 1 cycle (8 weeks) of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. | Every 8 weeks | 
| Overall Survival | Duration of time from enrollment on study until death | From enrolment till death on average up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lung Cancer, Carcinoma, small cell, Trisenox, Arsenic trioxide, phase II trial