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

Sponsor
Prince of Songkla University (Other)
Overall Status
Terminated
CT.gov ID
NCT01806649
Collaborator
(none)
5
1
1
34
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Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
5 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of BKM120; a Pan-PI3K Inhibitor in Patients With Esophageal Squamous Cell Carcinoma After Failure of First Line Chemotherapy
Actual Study Start Date :
Jul 1, 2013
Actual Primary Completion Date :
Apr 30, 2016
Actual Study Completion Date :
Apr 30, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: BKM120

BKM120, starting at 100 mg oral once daily

Drug: BKM120

Outcome Measures

Primary Outcome Measures

  1. disease control rate [16 weeks]

    16-week disease control rate using RECIST 1.1 criteria

Secondary Outcome Measures

  1. safety [each follow up visit, assessed up to 12 months]

    Safety data will be assessed at each study visit using CTCAE version 4.0

  2. progression-free survival [Time from day 1 to date of documented disease progression or death, assessed up to 12 months]

  3. overall survival [Time from day 1 to date of death, assessed up to 18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Songklanagarind Hospital, Prince of Songkla University Hat yai Songkhla Thailand 90110

Sponsors and Collaborators

  • Prince of Songkla University

Investigators

  • Principal Investigator: Arunee Dechaphunkul, MD, Prince of Songkla University, Thailand

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Arunee Dechaphunkul, Dr, Prince of Songkla University
ClinicalTrials.gov Identifier:
NCT01806649
Other Study ID Numbers:
  • 551691411
First Posted:
Mar 7, 2013
Last Update Posted:
Oct 11, 2021
Last Verified:
Oct 1, 2021
Keywords provided by Arunee Dechaphunkul, Dr, Prince of Songkla University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 11, 2021