BKM120 in Esophageal Squamous Cell Carcinoma After Failure of First Line Chemotherapy

Prince of Songkla University

Status and phase

Terminated

Phase 2

Conditions

Esophageal Cancer

Treatments

Drug: BKM120

Study type

Interventional

Funder types

Other

Identifiers

NCT01806649

551691411

Details and patient eligibility

About

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.

Enrollment

5 patients

Sex

All

Volunteers

No Healthy Volunteers

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.