BKM120 in Esophageal Squamous Cell Carcinoma After Failure of First Line Chemotherapy
Conditions
Esophageal Cancer
Conditions: official terms
Carcinoma, Squamous Cell - Esophageal Neoplasms
Conditions: Keywords
esophageal cancer, second line therapy, BKM120
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: BKM120
Type: Drug
Overall Status
Recruiting
Summary
There is a need for more effective therapy for patients with esophageal squamous cell carcinoma who developed disease progression after first line therapy. Currently, there is no standard second-line therapy for this disease.

BKM-120 is a pan-PI3K inhibitor currently tested in clinical trials. In a cellular model of oral-esophageal carcinogenesis, it has shown that EGFR overexpression activated PI3/AKT pathway. Therfore, there is interest to see the efficacy and safety of BKM120 in this setting.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: N/A
Gender: Both
Criteria: Inclusion Criteria:

- Patient has provided a signed Informed Consent Form (ICF) obtained prior to any screening procedure.

- Age ≥ 18 years old

- Histologically confirmed diagnosis of esophageal squamous cell carcinoma and available archival tissue for evaluation of further studies.

- Metastatic or unresectable disease

- Received one prior chemotherapy or biological therapy regimen for unresectable or metastatic disease

- More than 30 days since prior chemotherapy, surgery, radiotherapy, or investigational agents

- Measurable disease in at least 1 diameter by CT scan or MRI as per RECIST 1.1 criteria

- No evidence of brain metastasis

- ECOG ≤ 2

- Patient has adequate bone marrow and organ function

- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

- Platelets ≥ 100 x 109/L

- Hemoglobin ≥ 9.0 g/dL

- INR ≤ 2

- Potassium, calcium, magnesium within normal limits for the institution

- Serum Creatinine ≤ 1.5 x ULN or Creatinine clearance > 60 mL

- AST and ALT not more than 2.5 times ULN (not more than 5.0 times ULN if there is liver metastasis)

- Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)

- Fasting serum glucose < 1.5 times ULN

Exclusion Criteria:

- Patient has received previous treatment with PI3K inhibitors

- Patient has symptomatic CNS metastases

- Patients with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases > 28 days (including radiotherapy and/or surgery) prior to enrollment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.

- Patient has a concurrent malignancy or has a malignancy within 5 years of study enrollment, (with the exception of nonmelanoma skin cancer or cervical carcinoma in situ.

- Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 10 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9)

- Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) ≥ CTCAE grade 3 anxiety

- Patient is concurrently using other approved or investigational antineoplastic agent

- Patient has had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery

- Patient has poorly controlled diabetes mellitus(HbA1c > 8 %)

- Patient has active cardiac disease including any of the following:

- LVEF < 50%

- QTc > 480 msec on screening ECG (using the QTcF formula)

- Angina pectoris that requires the use of anti-anginal medication

- Ventricular arrhythmias except for benign premature ventricular contractions

- Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication

- Conduction abnormality requiring a pacemaker

- Valvular disease with documented compromise in cardiac function

- Symptomatic pericarditis

- Patient has a history of cardiac dysfunction including any of the following;

- Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function

- History of documented congestive heart failure (New York Heart Association functional classification III-IV)

- Documented cardiomyopathy

- Patient is currently receiving treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug

- Inability to swallow, impaired gastrointestinal (GI) function, or GI disease that would significantly alter the absorption of study drugs or preclude the use of oral medications

- Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate her participation in the clinical study (e.g.,chronic pancreatitis, active chronic hepatitis etc.)

- Patient is currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
Location
Songklanagarind Hospital, Prince of Songkla University
Hat yai, Songkhla, Thailand
Status: Recruiting
Contact: Arunee Dechaphunkul, MD - 6674 451469 - dr.arunee@gmail.com
Start Date
January 2013
Sponsors
Prince of Songkla University
Source
Prince of Songkla University
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page