Clinical trial NCT01470248: Study of Arsenic Trioxide in Small Cell Lung Cancer
Official title: A Single Arm, Two-Stage Phase II Study of Arsenic Trioxide in Previously Treated Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Cancer of Lung
Pulmonary Cancer
Pulmonary Neoplasms
Carcinoma, Small Cell
Keywords: Lung Cancer
Carcinoma, small cell
Trisenox
Arsenic trioxide
phase II trial
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Cephalon
name: Teva Pharmaceuticals USA
name: National Cancer Institute (NCI)
First posted: 2011-11-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Response Rate (RR)
timeFrame: Every 8 weeks
measure: Clinical Benefit Rate (CBR)
timeFrame: After completing at least 1 cycle (8 weeks) of treatment
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Every 8 weeks
measure: Overall Survival
timeFrame: From enrolment till death on average up to 2 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University Winship Cancer Institute
name: Taofeek Owonikoko, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Owonikoko TK, Zhang G, Kim HS, Stinson RM, Bechara R, Zhang C, Chen Z, Saba NF, Pakkala S, Pillai R, Deng X, Sun SY, Rossi MR, Sica GL, Ramalingam SS, Khuri FR. Patient-derived xenografts faithfully replicated clinical outcome in a phase II co-clinical trial of arsenic trioxide in relapsed small cell lung cancer. J Transl Med. 2016 May 3;14(1):111. doi: 10.1186/s12967-016-0861-5.