BKM120 in Advanced, Metastatic, or Recurrent Endometrial Cancers

NCT01550380 | Withdrawn Phase 2 DMC

• 1 other identifier: HCI47841
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II open label fixed dose study in subjects with advanced, metastatic, or refractory endometrial or ovarian, fallopian tube, or primary peritoneal cancer with PI3 kinase pathway activation as demonstrated by PIK3CA gene mutation, PTEN gene mutation, or PTEN null/low protein expression.

Conditions

Endometrial Cancer

Keywords

Endometrial cancer

Outcome Measures

Primary Outcomes (1)

• Response Rates of BKM120

  1. To assess response rate in patients with endometrial cancer treated with first line BKM120. 2. To assess response rate in patients with ovarian, fallopian tube, and primary peritoneal cancer treated with first line BKM120.

  Up to 20 months

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  Up to 20 months

Study Arms (1)

All participants

EXPERIMENTAL

Drug: BKM120

Interventions

BKM120 DRUG

NVP-BKM120 (BKM120) is an oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor belonging to the 2,6-dimorpholino pyrimidine derivative family.Supplied in 10mg or 50mg capsules. Starting dose: 100mg Once Daily

Also known as: 5-[2,6-Di(4-morpholinyl)-4-pyrimidinyl]-4-(trifluoromethyl)-2-pyridinamine

All participants

Eligibility Criteria

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

You may qualify if:

• Patients must have advanced, metastatic, recurrent, or persistent endometrial or ovarian, fallopian tube, or primary peritoneal cancer.
• Tumor must demonstrate PI3 Kinase pathway activation: defined as PIK3CA gene mutation, PTEN gene mutation, or PTEN null/low protein expression.
• Prior therapy:
• Patients must not have had cytotoxic therapy directed at metastatic disease. Adjuvant chemotherapy is permitted.
• Patients must NOT have received any non-cytotoxic therapy for metastatic or recurrent disease, except for hormonal therapy or immunologic therapy.
• Patients with persistent or refractory disease after upfront surgery and adjuvant chemotherapy are eligible.
• Age ≥ 18 years
• ECOG performance status ≤ 2
• Patients must have at least one site of measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for solid tumors or the appropriate disease classification/criteria for the target population)
• 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)

You may not qualify if:

• Patients who have received prior treatment with a P13K inhibitor.
• Patients with a known hypersensitivity to BKM120 or to its excipients.
• 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)
• ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
• 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 in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study unless overruled by the psychiatric assessment
• Patients with diarrhea ≥ CTCAE grade 2
• If patient is treated for diarrhea and it resolves to grade 1, patient may be enrolled.
• Patient has 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

• University of Utah: lead
• Novartis: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Theresa Werner, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2011
• First Posted: March 12, 2012
• Study Start: May 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: July 29, 2014

Record last verified: 2014-07

Locations

US (1)