A Study of BKM120 (Buparlisib) in Relapsed or Refractory Thymomas

NCT02220855 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IUCRO-0478
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Thymic tumors are rare tumors, but represent the most common tumors of the anterior mediastinum. Thymoma has an indolent course in advanced disease and has the propensity to spread to the pleura. In first line therapy, combination chemotherapy produces responses in approximately 80% of patients. A number of single agents have activity in recurrent disease, but none are curable. Patients with recurrent thymoma have limited treatment options, and thus novel target modalities are needed. At the Indiana University Simon Cancer Center (IUSCC), more patients with advance thymoma are seen than any other institution in the country. Our main hypothesis is the PI3K pathway is an important driver for growth and metastasis of thymoma and that inhibition of the PI3K pathway is expected to produce clinically meaningful response in patients with recurrent thymoma.

Conditions

Thymoma

Outcome Measures

Primary Outcomes (1)

• Percent of Patients With Objective Response

  Percent of patients with Objective response and the Binomial Exact 95% confidence interval. Objective response is defined as having a best response of Complete Response (defined as disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10mm) or Partial Response (defined as at least a 30% decrease in the sum of diameters of target lesions from the baseline sum diameters) by RECIST v1.1 criteria.

  up to three years

Secondary Outcomes (4)

• Treatment Related Adverse Events Grade 3 or Above

  up to three years

• Progression-free Survival Rate

  up to three years

• Percent of Patients Achieving Disease Control

  up to three years

• Overall Survival Rate

  up to three years

Study Arms (1)

BKM120

EXPERIMENTAL

BKM120, 100mg capsule for oral use, taken once daily for two or more months for a maximum of one year. Each cycle is 28 days.

Drug: BKM120

Interventions

BKM120 DRUG

BKM120

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of thymoma.
• At least one prior line of platin-based chemotherapy (unless refused or not tolerated).
• Documented progressive (clinical and/or objective) disease after the most recent systemic therapy regimen.
• Patients must not have received chemotherapy, radiation therapy, or undergone major surgery within 4 weeks prior to enrollment.
• 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 nonnodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 4 for the evaluation of measurable disease.
• Age ≥ 18 years
• ECOG performance status £ 2
• Patient must be able to swallow and retain oral medications
• Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb \>9 g/dL
• Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium ≥ the lower limit of normal
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present)
• 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)
• Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min

You may not qualify if:

• Patients who have received prior treatment with a P13K inhibitor.
• Patients with thymic carcinoma (formerly WHO Type C).
• Patients with a known hypersensitivity to BKM120 or to its excipients
• Patients with untreated brain metastases are excluded. However, patients with metastatic CNS tumors may participate in this trial, if the patient is \> 4 weeks from therapy completion (incl. radiation and/or surgery), is clinically stable at the time of study entry and is receiving low dosage corticosteroid therapy
• Patients with acute or chronic liver, renal disease or pancreatitis
• Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: • 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) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
• ≥ CTCAE grade 3 anxiety
• Meets the cut-off score of ≥ 12 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 in the PHQ-9 (independent of the total score of the PHQ-9)
• Patients with diarrhea ≥ CTCAE grade 2
• Patient has known active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)
• 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 arrhythmias requiring a pacemaker or not controlled with medication

Sponsors & Collaborators

• Patrick Joseph Loehrer Sr.: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Related Publications (2)

• Abu Zaid MI, Radovich M, Althouse S, Liu H, Spittler AJ, Solzak J, Badve S, Loehrer PJ Sr. A phase II study of buparlisib in relapsed or refractory thymomas. Front Oncol. 2022 Oct 18;12:891383. doi: 10.3389/fonc.2022.891383. eCollection 2022.

  PMID: 36330484 DERIVED

• Radovich M, Solzak JP, Hancock BA, Conces ML, Atale R, Porter RF, Zhu J, Glasscock J, Kesler KA, Badve SS, Schneider BP, Loehrer PJ. A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas. Br J Cancer. 2016 Feb 16;114(4):477-84. doi: 10.1038/bjc.2015.425. Epub 2016 Jan 14.

  PMID: 26766736 DERIVED

MeSH Terms

Conditions

Thymoma

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Patrick Loehrer
• Organization: IndianaU

ploehrer@iu.edu

317-944-0920

Study Officials

• Patrick Loehrer, M.D.

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Dean for Cancer Research

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 20, 2014
• Study Start: October 1, 2014
• Primary Completion: March 27, 2017
• Study Completion: March 9, 2021
• Last Updated: April 11, 2022
• Results First Posted: December 19, 2018

Record last verified: 2022-03

Locations

US (1)