Endometrial Cancer
Conditions
Keywords
Endometrial cancer
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.
Detailed description
Given the mechanisms of action and the safety profiles and tolerability of BKM120 (NVP-BKM120), the use of this agent may provide benefit to patients with endometrial and ovarian cancer. Endometrial and ovarian cancer are leading causes of cancer death in women and there are limited treatment options for those with metastatic or refractory disease. Alterations of the PI3K/PTEN/Akt pathway have been identified in many cancers, including endometrial and ovarian cancers. Tumors with PI3K mutations have demonstrated sensitivity to this compound therefore justifying use of this agent in subjects with endometrial or ovarian, fallopian tube, or primary peritoneal cancer. Therefore use of this agent in cancer patients with PI3 kinase pathway activation offers a reasonable treatment option. Patients will be initially treated with single agent BKM120 for 28 days at a dose of 100mg per day. CT response will be adjudged post BKM120 therapy at day 28. If there is no significant progression on CT scan, patients will be continued on BKM120 for another two cycles (28 days per cycle \[+/- 3 days\]). Response assessments will then be done at that time (after the third 28 day cycle). If there is no significant progression on CT scan, then the patients will continue BKM120 with response assessments using standard CT criteria every two cycles (28 days per cycle \[+/- 3 days\]) thereafter. If disease progression is observed, patient will have completed the study. Patient will be seen within 30 days for end of treatment visit.
Interventions
DRUGBKM120
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
Sponsors
Novartis
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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) * Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min * Serum amylase ≤ ULN * Serum lipase ≤ ULN * Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L) * Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential * INR ≤ 2 * Able to provide informed consent & have signed an approved consent form that conforms to federal & institutional guidelines.
Exclusion criteria
* Patients who have received prior treatment with a P13K inhibitor. * Patients with a known hypersensitivity to BKM120 or to its excipients. * Patients with untreated brain metastases are excluded. However, patients with metastatic Central Nervous System (CNS) tumors may participate in this trial, if the patient is \> 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy (other than stable low dose corticosteroid therapy as outlined in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates of BKM120 | Up to 20 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 20 months | 1. To determine the progression free survival (PFS) in patients with endometrial cancer treated with first line BKM120. 2. To document the non-progression rate at 12 weeks in patients with endometrial cancer treated with first line BKM120. 3. To determine the progression free survival (PFS) in patients with ovarian, fallopian tube, and primary peritoneal cancer treated with first line BKM120. 4. To document the non-progression rate at 12 weeks in patients with ovarian, fallopian tube, and primary peritoneal cancer treated with first line BKM120. |
Countries
United States
Outcome results
None listed